http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10557576&dopt=Abstract
Prescrire
Int 1999 Feb;8(39):29-31
Quinolones
and pregnancy: worrying animal findings, few clinical
data.
(1) Follow-up studies of approximately 1,000 women exposed
to quinolones during pregnancy show no increase in the
risk of malformations, miscarriage, prematurity, intrauterine
growth retardation or postnatal disorders, but there
are not enough data to draw firm conclusions.
(2) Teratogenic effects have been
observed in animals treated with the oldest quinolones
(flumequine, nalidixic acid and pipemidic acid) and
also with sparfloxacin, a fluoroquinolone.
(3) Cartilage damage after postnatal exposure to quinolones
in animals and humans has been reported.
(4) Alternatives to quinolones can almost always be
found for pregnant women.
(5) Accidental exposure to quinolones during pregnancy
does not warrant termination.
PMID: 10557576 [PubMed - indexed for
MEDLINE]
|
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1667390&dopt=Abstract
Food
Addit Contam 1991 Nov-Dec;8(6):777-80
Reservoir
of quinolone residues in fish.
Steffenak I, Hormazabal V, Yndestad M.
Department of Food Hygiene, Norwegian College of Veterinary
Medicine, Oslo.
Different tissues from salmon treated with the quinolones
oxolinic acid, flumequine,
enrofloxacin and sarafloxacin were analysed in search
of possible reservoirs of the drugs. Residues of oxolinic
acid and flumequine seem to be
especially bound to bone, enrofloxacin to skin,
and sarafloxacin to both skin and bone. The
results showed that residues of these drugs were present
in the fish for prolonged periods after the end of treatment.
PMID: 1667390 [PubMed - indexed for
MEDLINE]
|
European
Commission: Not allowed to be used as an active ingredient
after July 25, 2003.
-- Flumequine's production and use as an antibiotic(1)
and antibiotic feed-additive on
fish farms(2) may result in its release to the
environment through various waste streams(SRC). [(1)
Budavari S, ed; The Merck Index. 13th ed. Whitehouse
Station, NJ: Merck and Co., Inc. p. 732 (2001) (2) Halling-Sorensen
B et al; Chemosphere 36: 357-93 (1998)]
-- Authorized or allowed for use in
aquaculture (2 day withdrawal time in France).
... Registered or approved for use in aquatic or fishery
situations in Japan (20 mg/kg per day) [Kirk-Othmer
Encyclopedia of Chemical Technology. 4th ed. Volumes
1: New York, NY. John Wiley and Sons, 1991-Present.,p.
V3 (1992) 618]
-- Ref:
Hazardous Substance Data Bank for Flumequine. Available
at Toxnet.
Effect
of cooking on residues of the quinolones oxolinic acid
and flumequine in fish.
Authors: STEFFENAK I HORMAZABAL V YNDESTAD M
Author Address: Dep. Food Hygiene, Norw. Coll. Vet. Med.,
P.O. Box 8146-Dep., N-0033 Oslo 1, Norway.
Source: ACTA VETERINARIA SCANDINAVICA; 35 (3). 1994.
299-301.
Abstract: The effect of cooking
on residues of the quinolones oxolinic acid and flumequine
in fish was investigated. Salmon containing residues of
oxolinic acid and flumequine was boiled or baked in the
oven. Samples of raw and cooked muscle, skin, and bone,
as well as of the water in which the fish was boiled and
juice from the baked fish, were analysed. Oxolinic acid
and flumequine did not degrade at the temperatures reached
when cooking the fish. However,
fish muscle free from drug residues may be contaminated
during boiling and baking due to leakage of the drug from
reservoirs in the fish. |
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15720004&query_hl=1
Environ Toxicol Chem.
2005 Feb;24(2):423-30.
Toxicity of fluoroquinolone antibiotics
to aquatic organisms.
Robinson AA, Belden
JB, Lydy MJ.
Fisheries and Illinois
Aquaculture Center and Department of Zoology, Southern Illiois
University at Carbondale, Carbondale, Illinois 62901, USA.
Toxicity tests were
performed with seven fluoroquinolone antibiotics, ciprofloxacin,
lomefloxacin, ofloxacin, levofloxacin, clinafloxacin, enrofloxacin,
and flumequine, on five aquatic
organisms. Overall toxicity values ranged from 7.9 to 23,000
microg/L. The cyanobacterium Microcystis aeruginosa was the
most sensitive organism (5-d growth and reproduction, effective
concentrations [EC50s] ranging from 7.9 to 1,960 microg/L and
a median of 49 microg/L), followed by duckweed (Lemna minor,
7-d reproduction, EC50 values ranged from 53 to 2,470 microg/L
with a median of 106 microg/L) and the green alga Pseudokirchneriella
subcapitata (3-d growth and reproduction, EC50 values ranged
from 1,100 to 22,700 microg/L with a median 7,400 microg/L).
Results from tests with the crustacean Daphnia magna (48-h survival)
and fathead minnow (Pimephales promelas, 7-d early life stage
survival and growth) showed limited toxicity with no-observed-effect
concentrations at or near 10 mg/L. Fish dry weights obtained
in the ciprofloxacin, levofloxacin, and ofloxacin treatments
(10 mg/L) were significantly higher than in control fish. The
hazard of adverse effects occurring to the tested organisms
in the environment was quantified by using hazard quotients.
An estimated environmental concentration of 1 microg/L was chosen
based on measured environmental concentrations previously reported
in surface water; at this level, only M. aeruginosa may be at
risk in surface water. However, the selective
toxicity of these compounds may have implications for aquatic
community structure.
PMID: 15720004
[PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15699587&query_hl=1
J Vet Med Sci. 2005
Jan;67(1):7-12.
The prevalence and antimicrobial susceptibilities
of Salmonella and Campylobacter in ducks in Taiwan.
Tsai HJ, Hsiang PH.
Graduate Institute
of Veterinary Medicine, National Taiwan University, Taipei,
Taiwan.
Cloacal swabs were
sampled from 100 duck farms in Taiwan between March 2000 and
January 2001 for isolation and standard cultivation of Salmonella
spp. and thermophilic Campylobacter spp. Salmonella spp. were
isolated from 4.6% (91/2000) of ducks from 20% (20/100) of duck
farms. Ten serotypes of Salmonella enterica were identified:
S. Potsdam (31.9% of isolates), S. Dusseldorf (18.7%), S. Indiana
(14.3%), S. Typhimurium (7.7%), S. Hadar (5.5%), S. Newport
(4.4%), S. Derby (4.4%), S. Montevideo (2.2%), S. Schwarzengrund
(2.2%), and S. Asinnine (1.1%). Isolation of S. Asinnine or
S. Indiana from poultry had not hitherto been described in Taiwan.
The salmonella isolation rate in ducklings under two weeks of
age was significantly higher than the other age groups (P<0.05).
Campylobacter spp. were isolated from 43.5% (1045/2400) of ducks
from 92% (92/100) of duck farms. Among them, 991 isolates (94.8%)
were identified as C. jejuni and 54 isolates (5.2%) as C. coli.
The campylobacter isolation rate in ducklings under two weeks
of age was significantly lower than other age groups (P<0.05).
Antimicrobial susceptibility testing was conducted by the disk
diffusion and E- test methods. The results indicated that Salmonella
isolates were 100% susceptible to amikacin, amoxicillin/clavulanic
acid, ceftraxone, cephalothin, ciprofloxacin, norfloxacin, ofloxacin,
and polymyxin B. A markedly higher antimicrobial
resistance to amoxicillin, florfenicol, flumequine,
josamicin/trimethoprim, nalidixic acid, nitrofurantoin, norfloxacin,
ofloxacin, polymyxin B, sulfamethoxazole/trimethoprim and tetracycline
was found in campylobacter isolates.
PMID: 15699587
[PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16153786&query_hl=1
Vet Microbiol. 2005
Oct 31;110(3-4):239-44.
Isolation and molecular characterization
of quinolone resistant Salmonella spp. from poultry farms.
San Martin B, Lapierre
L, Toro C, Bravo V, Cornejo J, Hormazabal JC, Borie C.
Laboratorio de Farmacologia
Veterinaria, Facultad de Ciencias Veterinarias y Pecuarias,
Universidad de Chile, Santa Rosa 11735, La Pintana, Santiago,
Chile.
The antimicrobial
susceptibility of 94 Salmonella strains isolated from different
poultry farms in Chile (broiler and laggin hens) were analyzed
by the dilution plates method. Thirty-nine
of them were resistant to flumequine, nalidixic acid
and oxolinic acid with MIC values higher than 64mug/ml. These
quinolone resistant strains were analyzed in order to determine
the presence of mutations in the QRDR region of gyrA gene by
AS-PCR-RFLP analysis. 51.3% of the strains showed mutations
at codon Ser 83 and 41.0% showed mutations at codon Asp 87.
No mutations were observed on codon Gly 81. These mutations
were confirmed by sequenciation of one representative strain
from different RFLP pattern. Likewise, no double mutations were
observed. Over 90% of the quinolone resistant strains presented
mutations at the QRDR region of the gyrA gene. Three phenotypically
resistant strains did not show any mutations on the QRDR region
of gyrA gene. However, other molecular resistant mechanism could
be involve. This is the first study that
demonstrate the emergency of quinolone and fluoroquinolone resistance
in Chilean Salmonella strains isolated from poultry thus indicating
the requirement of monitoring programmes in veterinary medicine.
PMID: 16153786 [PubMed
- in process]
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16162248&query_hl=1
J Appl Microbiol.
2005;99(4):954-9.
Effect of quinolone treatment on selection
and persistence of quinolone-resistant Escherichia coli in swine
faecal flora.
Belloc C, Lam DN,
Pellerin JL, Beaudeau F, Laval A.
National Veterinary
School, Nantes cedex, France. belloc@vet-nantes.fr
AIMS: To study the
effect of oral administration of a quinolone on emergence of
resistance in an indicator bacterial species from faecal flora.
METHODS AND RESULTS: Quinolone resistance was studied in Escherichia
coli obtained from the faecal contents of pigs housed in nine
commercial farrow-to-finish herds in France after administration
of flumequine to sows. The percentage of quinolone-resistant
E. coli increased in the faeces of sows after administration
of flumequine (mean 21.78% at day 7 vs 6.42% before treatment
for nalidixic acid) and then decreased (mean 12.6 and 10.4 at
days 30 and 60, respectively for nalidixic acid), being not
significantly different from initial values 1 month post-treatment.
In young pigs, the proportion of resistant strains was lower
and decreased over rearing period. Moreover, changes over time
of both total E. coli and the proportion of resistant bacteria
exhibited great inter-individual variability.
CONCLUSIONS: Restoration of susceptible
faecal flora occurred within 2 months after flumequine treatment.
SIGNIFICANCE AND IMPACT OF THE STUDY: Effect of flumequine treatment
of sows on the quinolone resistance of faecal E. coli of both
sows and their progeny is noticeable but transitory.
PMID: 16162248 [PubMed
- in process]
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15081752
Sci Total Environ. 2004
Apr 25;322(1-3):243-53.
The
bryophyte Fontinalis antipyretica Hedw. bioaccumulates oxytetracycline,
flumequine and oxolinic acid in the freshwater environment.
Delepee
R, Pouliquen H, Le Bris H.
Ecole Nationale Veterinaire de Nantes, UMR INRA/ENVN Chimiotherapie
Aquacole et Environnement, B.P. 40706, 44307 Nantes Cedex 03,
France. rdelepee@vet-nantes.fr
In recent years, the fate of pharmacological substances in the
aquatic environment have been more and more studied. Oxolinic
acid (OA), flumequine (FLU) and
oxytetracycline (OTC) are commonly used
antibacterial agents. A large amount of these drugs is
released into water directly by dissolved fraction and indirectly
in urine and feces. Monitoring these compounds in the freshwater
environment is difficult because of the lack of suitable indicators.
The aim of this work was to evaluate the OA, FLU and OTC bioaccumulation
abilities of Fontinalis antipyretica Hedw., known for heavy
metal bioaccumulation. The experiment described was decomposed
for two times: a 10-days accumulation period during which bryophytes
were in contact with antibiotics and a 15-days post-exposure
period during which bryophytes were in water with no antibiotic.
This experiment showed that this bryophyte strongly accumulates
OA, FLU and OTC in freshwater. Bioaccumulation factors (ratio
of concentrations in bryophyte and water) ranged between 75
and 450. Moreover, OA, FLU and OTC persisted in the bryophyte
for a long time with clearance between 0.19 and 3.04 ng/g/day.
Mean residence times ranged between 18 and 59 days. Accumulation
and decontamination mechanism models were proposed.
PMID: 15081752 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15291461&query_hl=1
J Agric Food Chem. 2004 Aug 11;52(16):4975-8.
Development of an indirect competitive
ELISA for flumequine residues in raw milk using chicken egg
yolk antibodies.
Van Coillie E, De Block J, Reybroeck
W.
Ministry of the Flemish Community, Agricultural Research Centre
Ghent (CLO), Department of Animal Product Quality and Transformation
Technology (DVK), Brusselsesteenweg 370, B-9090 Melle, Belgium.
e.vancoillie@clo.fgov.be
To detect flumequine in raw milk, an indirect competitive enzyme-linked
immunosorbent assay (ELISA) was developed. By carbodiimide conjugation,
flumequine was conjugated to cationized bovine serum albumin
(cBSA-flumequine) and to cationized ovalbumin (cOVA-flumequine).
For the immunization of chickens, cBSA-flumequine was used,
which allowed the isolation of specific chicken egg yolk immunoglobulins
(IgY) for flumequine. As the coating antigen in the immunoassay,
cOVA-flumequine was used. In the indirect competitive assay,
standard flumequine was incubated together with the anti-flumequine
antibodies. The antibody by which the lowest concentration of
free flumequine that gives 50% inhibition of binding (IC50)
was found in aqueous dilution was further tested for the applicability
to detect flumequine in raw milk. An IC50 level in milk was
reached that was about 5 times lower than in aqueous solution.
So flumequine can be detected directly
in raw milk at maximum residue level (50 microg/kg).
No cross-reactivity was noticed with various related quinolones.
PMID: 15291461 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15314197
J Med Microbiol.
2004 Sep;53(Pt 9):895-901.
Mechanisms of quinolone resistance and clonal relationship
among Aeromonas salmonicida strains isolated from reared fish
with furunculosis.
Giraud
E, Blanc G, Bouju-Albert A, Weill FX, Donnay-Moreno C.
Unite Mixte de Recherche
INRA-ENVN Chimiotherapie Aquacole et Environnement, Ecole Nationale
Veterinaire, Atlanpole, La Chantrerie, BP40706, 44307 Nantes,
Cedex 03, France.
The mechanisms of
resistance to quinolone and epidemiological relationships among
A. salmonicida strains isolated from diseased fish in French
marine farms from 1998 to 2000 were investigated. The quinolone
resistance-determining regions of the gyrA and parC genes of
12 clinical A. salmonicida isolates with different levels of
quinolone susceptibility were sequenced. MICs were determined
in the presence of the efflux pump inhibitor (EPI) Phe-Arg beta-naphthylamide
and E(max) values (MIC without EPI/MIC in the presence of EPI)
were calculated. Isolates fell into two classes: (i) those that
had a wild-type gyrA gene with oxolinic acid MIC </= 0.5,
flumequine MIC </= 1 and ciprofloxacin MIC </= 0.25 micro
g ml(-1); and (ii) those that had a single mutation in gyrA
encoding Asp-87 --> Asn with oxolinic acid MIC >/= 2,
flumequine MIC >/= 4 and ciprofloxacin MIC >/= 0.125 micro
g ml(-1). No mutations were found in parC. High E(max) values
obtained for flumequine and oxolinic acid (up to 16 and 8, respectively,
for the most resistant isolates of the two classes) indicated
an important contribution of efflux to the resistance phenotype.
Flumequine accumulation experiments confirmed
that high E(max) values were associated with a much lower level
of accumulation. PCR/RFLP assays conducted on 34 additional
isolates showed the presence of a mutation at codon 87 of gyrA
in nearly all the quinolone-resistant isolates. This finding,
together with PFGE typing results, strongly suggests a common
clonal origin of these quinolone-resistant isolates.
PMID: 15314197
[PubMed - in process]
Chemosphere; Volume 54, Issue 5 , February 2004,
Pages 661-668
Preliminary investigation on the environmental
occurrence and effects of antibiotics used in aquaculture in
Italy
Giorgia Mary Lalumera (a), Davide Calamari
(a), Paolo Galli (b), Sara Castiglioni (a), Giuseppe Crosa (a)
and Roberto Fanelli (c)
a Environment Research Group, Department of Structural and
Functional Biology (DBSF), University of Insubria, Via J.H.
Dunant, 3-21100, Varese, Italy
b Department of Biotechnology and Bioscience, University of
Milano-Bicocca, Piazza della Scienza, 2-20126, Milan, Italy
c Department of Environmental Health Sciences, Institute for
Pharmacological Research "Mario Negri", Via Eritrea,
62-20157, Milan, Italy
Received 3 July 2002; revised 18 July 2003; accepted
5 August 2003. ; Available online 3 October 2003.
A preliminary investigation has been carried out on the occurrence
and effects of antibiotics used in Italian aquaculture with
the objective of identifying priorities for monitoring programmes.
According to the information available on the most pertinent
and diffuse fish diseases and their related therapies, the presence
of flumequine and oxytetracycline in sediments sampled from
two trout farms and three sea-bass farms and in their surrounding
environments was selected for an analytical investigation. The
concentrations of oxytetracycline and flumequine varied up to
a maximum of 246.3 and 578.8 g/kg d.w., respectively. Flumequine
was seen to have the highest toxicity in a bioluminescence assay
with EC50 values varying within the range of 12–15 mg/l,
while the EC50 values for oxytetracycline were within
the range of 121–139 mg/l.
The results of the present study indicate flumequine and oxytetracycline
as priority chemicals to be monitored for possible environmental
side effects of aquaculture in Italy. Apart from peak concentrations
the chronic presence of flumequine and oxytetracycline in sediments
both inside and outside farms should also be considered. In
spite of the potential risks related to the use of antibiotics,
the concentrations found in the sediments of the studied fish
farms are significantly lower than those found in other areas.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=12887606
J Vet Pharmacol Ther. 2003 Aug;26(4):253-8.
Comparative effects of fluoroquinolones on subsets of T lymphocytes
in normothermic and hyperthermic mice.
Szczypka M, Obminska-Mrukowicz B.
Department of Biochemistry, Pharmacology and Toxicology, Faculty
of Veterinary Medicine, Agricultural University, Wroclaw, Poland.
marianna@ozi.ar.wroc.pl
The subsets of T lymphocytes in thymus, spleen and mesenteric
lymph nodes were investigated in normothermic and hyperthermic
mice treated with fluoroquinolones administered orally six times
at 24 h intervals at doses of 15 or 75 mg/kg (flumequine, norfloxacin
and ciprofloxacin) and 5 or 25 mg/kg (enrofloxacin). It has
been found that fluoroquinolones can modulate CD3+, CD4+ and
CD8+ marker expression on thymocytes, splenocytes and lymphocytes
of mesenteric lymph nodes. Flumequine
(15 mg/kg) decreased the percentage of immature CD4+CD8+ thymic
cells and increased the percentage of mature CD4+ and CD8+.
When the dose of flumequine was increased to 75 mg/kg a reduction
in the maturation of thymocytes was observed. Administration
of flumequine, norfloxacin and ciprofloxacin, irrespective of
doses applied, increased the percentages of CD3+ splenocytes
of CD4+ spleen cells. Exposure to enrofloxacin decreased
the percentage of T helper-inducer cells.
Flumequine and ciprofloxacin augmented the percentage of CD3+
mesenteric lymph node cells and increased the percentage of
CD8+ cells. In contrast, norfloxacin and enrofloxacin
decreased the percentage of CD3+ mesenteric lymph node cells
and the percentage of CD4+ cells. Lipopolysaccharide (LPS) from
E. coli (25 micro g/mouse) increased the percentage of single-positive
CD4+ thymocytes, but did not affect the percentage of CD3+,
CD4+ and CD8+ splenocytes and mesenteric lymph node cells.
Flumequine and ciprofloxacin administered to mice pior to LPS
potentiated its stimulant effect on the maturation of thymic
cells ( increased percentage of mature CD4+ and CD8+ thymocytes).
Pre-treatment with norfloxacin or enrofloxacin either reduced
or did not modify the stimulant effect of LPS on maturation
of thymic cells. Flumequine, norfloxacin,
enrofloxacin and ciprofloxacin administered prior to LPS decreased
the percentage of CD8+ splenocytes and increased the percentage
of CD4+ spleen cells. Norfloxacin and ciprofloxacin at
a dose of 75 mg/kg reduced the percentage of CD8+ mesenteric
lymph node cells in hyperthermic mice. Pretreatment with norfloxacin
at a dose of 15 mg/kg augmented the percentage of mesenteric
lymph node cells. It was concluded that the modulating effects
of fluoroquinolones depends on the chemial structure of drugs,
dose administered as well as immunologic status.
PMID: 12887606 [PubMed - indexed for MEDLINE]
Free
full report at http://www.eurosurveillance.org/em/v08n02/0802-222.asp
Euro Surveill. 2003
Feb;8(2):31-5.
Explosive
increase of Salmonella Java in poultry in the Netherlands:
consequences for public health.
van
Pelt W, van der Zee H, Wannet WJ, van de Giessen AW, Mevius
DJ, Bolder NM, Komijn RE, van Duynhoven YT.
In the Netherlands
Salmonella Paratyphi B variant Java increased in poultry from
less than 2% of all isolates before 1996 to 60% in 2002. Despite
exposure to contaminated meat is high, human patients with Java
infection are rare (0.3% of all isolates). However, 50% of the
human isolates showed PFGE profiles identical to the poultry
clone. Resistance to flumequin in S. Java
increased from 3% between 1996-2000 to 19% in 2001, and 39%
in 2002, while that of other serotypes in poultry remained
at about 7%. S. Java is also fast becoming less sensitive to
ciprofloxacin.
Publication Types:
* Editorial
PMID: 12631972
[PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=12718468
Dis Aquat Organ.
2003 Mar 17;54(1):35-41.
Pharmacokinetics
of flumequine and in vitro activity against bacterial pathogens
of gilthead sea bream Sparus aurata.
Rigos
G, Tyrpenou AE, Nengas I, Yiagnisis M, Koutsodimou M, Alexis
M, Troisi GM.
Laboratory of Fish
Nutrition and Pathology, National Centre for Marine Research,
Aghios Kosmas 16604, Ellinikon, Attiki, Greece. grigos@ncmr.gr
The present study
investigated the kinetic profile of flumequine (FLU) in gilthead
sea bream Sparus aurata (170 g) held at 19 degrees C and evaluated
its in vitro efficacy against important bacterial diseases in
Mediterranean mariculture. Following a single intravascular
injection (10 mg kg(-1) fish), the distribution half-life (t1/2alpha)
and the half-life of the terminal phase of elimination (t1/2gamma)
of the drug were 0.2 and 30 h respectively. Tissue penetration
of FLU was low, since both the apparent distribution volume
of the drug at steady-state (Vd(SS)) and the apparent volume
of the central compartment (Vc) were small (0.57 and 0.15 l
kg(-1)). The mean residence time (MRT) was short (11 h) and
the total clearance (CL(T)) of the drug was slow (0.05 l kg(-1)
h(-1)). Following oral administration (20 mg kg(-1)), the bioavailability
(F %) of FLU was 29% and the maximum plasma concentration was
1.7 microg ml(-1). The minimum inhibitory concentration (MIC)
of the drug in distilled water supplemented with 2% NaCl against
Vibrio anguillarum Serotype 1b, Photobacterium damsela ssp.
piscicida, V. alginolyticus, V. damsela and V. fluvialis was
0.15, 0.3, 1.2, 0.019 and 0.15 microg ml(-1) respectively. The
addition however of 10 mM Ca2+ and 55 mM Mg2+ to the medium
resulted in an 8- to >120-fold reduction in FLU activity.
The results indicate that FLU has an adequate
kinetic profile in gilthead sea bream and that marine cations
induce a significant impact on the activity of FLU, rendering
its use against bacterial pathogens questionable.
PMID: 12718468
[PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12377980&dopt=Abstract
Toxicol Sci 2002
Oct;69(2):317-21
Mechanistic
study on flumequine hepatocarcinogenicity
focusing on DNA damage in mice.
Kashida
Y, Sasaki YF, Ohsawa K, Yokohama N, Takahashi A, Watanabe T,
Mitsumori K.
Laboratory of Veterinary Pathology, Tokyo University of Agriculture
and Technology, 3-5-8 Saiwai-cho, Fuchu, Tokyo 183-8509, Japan.
In order to elucidate the tumor-initiating potential of flumequine
(FL) in the liver, male C3H mice were given dietary administration
of 4000 ppm FL throughout the study or for 2 weeks at the initiation
stage, and then received 2 intraperitoneal injections of D-galactosamine
(Gal) at weeks 2 and 5, with or without 500 ppm phenobarbital
(PB) in their drinking water for 13 weeks to provide tumor-promoting
effects. Hepatocellular foci were observed in 2 out of 8 and
6 out of 7 animals in the FL/PB + Gal and FL/FL + Gal groups,
respectively. In addition, in an alkaline single-cell gel electrophoresis
(comet) assay that was performed using adult, infant, or partial
hepatectomized male ddY mice to evaluate the potential of FL
at 500 mg/kg or less, to act as a DNA damaging agent.
FL induced dose-dependent DNA damage in the stomach, colon,
and urinary bladder of adult mice at 3 h but not at 24 h after
its administration. Similarly,
DNA damage was noted in the regenerating liver and the livers
of infant mice at the 3 h time point. Furthermore, in
in vitro assays that were conducted to investigate the potential
of FL to inhibit eukaryotic topoisomerase II, which is responsible
for the double-strand DNA breakage reaction as well as bacterial
gyrase, inhibitory effects of FL on topoisomerase II were high
relative to the influence on bacterial gyrase. The
results of our studies thus strongly suggest that FL has initiating
potential in the livers of mice that is attributable to its
induction of DNA strand breaks.
PMID: 12377980 [PubMed - in process]
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12185306&dopt=Abstract
J Vet Med Sci 2002
Jul;64(7):551-6
Susceptibility
of liver proliferative lesions in heterozygous p53 deficient
CBA mice to various carcinogens.
Uehara
T, Kashida Y, Watanabe T, Yasuhara K, Onodera H, Hirose M, Mitsumori
K.
Laboratory of Veterinary Pathology, Tokyo University of Agriculture
and Technology, 3-5-8 Saiwai-cho, Fuchu, Tokyo 158-8501, Japan.
To investigate the liver tumorigenic sensitivity to various
carcinogens in heterozygous p53 deficient [p53 (+/-)] CBA mice
and their wild-type littermates [p53 (+/+) mice], 71 p53 (+/-)
and 74 p53 (+/+) CBA mice (male, 6-12 weeks of age) were given
diet containing 4,000 or 0 ppm flumequine
(FL) for 26 weeks or a single intraperitoneal injection
of 5 mg/kg body weights dimethylnitrosamine (DMN) at start of
the study in Exp. 1, diet containing 6,000 or 0 ppm di(2-ethylhexyl)-phthalate
(DEHP) for 26 weeks in Exp. 2, or diet containing 12,000, 6,000
or 0 ppm phenolphthalein (PhP) for 26 weeks in Exp. 3. All surviving
animals of these groups were killed after completion of treatment
of the test substances for 26 weeks. In the
FL groups, the incidences of hepatocellular altered foci
in p53 (+/-) mice, the multiplicities of those in p53 (+/-)
and p53 (+/+) mice were significantly
increased as compared to the corresponding control groups.
The incidences and multiplicities of altered foci in the DMN
groups were higher than those in the corresponding control groups
in p53 (+/-) and p53 (+/+) mice, but no significant differences
were indicated between the groups. There were no significant
differences in the incidences, multiplicities and proliferating
cell nuclear antigen labeling indices of altered foci in the
FL or DMN groups between p53 (+/-)
and p53 (+/+) mice. There were no significant differences in
the incidences and multiplicities of altered foci between the
DEHP or PhP and control groups. The present results suggest
that p53 gene knocked out heterozygously does not enhance the
chemical hepatocarcinogenesis in CBA mice.
PMID: 12185306 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12180678&dopt=Abstract
J AOAC Int 2002
Jul-Aug;85(4):853-60
Quantitative
LC/MS-MS determination of sulfonamides and some other antibiotics
in honey.
Kaufmann
A, Roth S, Ryser B, Widmer M, Guggisberg D.
Official Food Control Authority of the Canton of Zurich (Kantonales
Labor Zurich), Switzerland. anton.kaufmann@klzh.ch
A simple and rapid method was developed for the determination
of 20 antibiotics (sulfonamides, tetacyclines, and flumequine)
in honey by liquid chromatography tandem mass spectrometry.
The proposed method is sensitive (limit of detection 0.5 to
10 ppb for the various antibiotics) and selective. A hydrolysis
step ensures the liberation of sugar-bound sulfonamides. The
approach has been used to analyze some 300 honey samples. A
number of them were found to have exceeded the Swiss limit of
50 ppb.
PMID: 12180678 [PubMed - in process]
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12093040&dopt=Abstract
Dis Aquat Organ
2002 Apr 24;49(1):39-44
Flumequine
in Atlantic salmon Salmo salar: disposition in fish held in
sea water versus fresh water.
Sohlber
S, Ingebrigtsen K, Hansen MK, Hayton WL, Horsberg TE.
Department of Pharmacology, Microbiology and Food Hygiene, The
Norwegian School of Veterinary Science, Oslo. sidsel.sohlberg@veths.no
14C-labeled flumequine was administered
as a single oral (5 mg kg(-1), 86 microCi kg(-1)) or intravenous
(5 mg kg(-1), 82 microCi kg(-1)) dose to Atlantic salmon Salmo
salar held in sea water or in fresh water. The absorption, tissue
distribution and elimination were determined by means of liquid
scintillation counting and whole-body autoradiography. The drug
was rapidly absorbed and extensively distributed in all groups
of fish. Radiolabeled compound was present in blood and muscle
for more than 8 wk in the freshwater groups. In the seawater
groups, however, no radioactivity was detected in the blood
and muscle after 4 d and 2 wk, respectively.
It was concluded that flumequine was eliminated at a substantially
higher rate from Atlantic salmon in sea water than in fresh
water.
PMID: 12093040 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12019949&dopt=Abstract
J Vet Med B Infect
Dis Vet Public Health 2002 Apr;49(3):160-2
Bacterial
resistance to quinolone antibiotics in Poland.
Rolinski
Z, Kowalski C, Zan R, Sobol M.
Department of Pharmacology, Faculty of Veterinary Medicine,
Agricultural University, Lublin, Poland. cezaryk@agros.ar.lublin.pl
The resistance of 167 pathogenic bacteria of animal origin to
quinolones was determined by the disc diffusion method, and
by the minimum inhibitory concentration (MIC) test. The highest
resistance of Escherichia coli was found to be against nalidixic
acid (NA), 49.1% and flumequine
(FLU), 38.2%. The sensitivity of
the strains were: ciprofloxacin (CIP; 81.8%); enrofloxacin (ENR;
81.8%); norfloxacin (NOR; 80.0%); and pefloxacin (PE; 76.4%).
Salmonella spp. showed 100% sensitivity to CIP, ENR, NOR and
PE. A high resistance percentage in the cases of: FLU
(86.7%); PE (50.0%); and CIP (26.65%) distinguished the Streptococcus
spp. The highest percentage sensitivity of Staphylococci was
found with three fluoroquinolones: CIP, ENR and NOR, 94.3% each
(66 strains). The studies did not indicate that a total cross-resistance
might occur between the examined quinolones.
PMID: 12019949 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11804417&dopt=Abstract
Dis Aquat Organ 2001
Dec 5;47(3):183-91
Disposition
of 14C-flumequine in eel Anguilla
anguilla, turbot Scophthalmus maximus and halibut Hippoglossus
hippoglossus after oral and intravenous administration.
Hansen
MK, Ingebrigtsen K, Hayton WL, Horsberg TE.
Department of Pharmacology, Microbiology and Food Hygiene, The
Norwegian School of Veterinary Science, Oslo. magne.hansen@veths.no
The absorption, distribution and elimination of 14C-labelled
flumequine were studied using whole
body autoradiography and liquid scintillation counting. Flumequine
was administered to eel Anguilla anguilla, turbot Scophthalmus
maximus and halibut Hippoglossus hippoglossus intravenously
and orally as a single dose of 5 mg kg(-1), corresponding to
0.1 mCi kg(-1). The turbot and halibut studies were performed
in salt water (salinity of 32%) at temperatures of 16 +/- 1
degrees C (turbot) and 9.5 +/- 0.5 degrees C (halibut). The
eel study was conducted in fresh water at 23 +/- 1 degrees C.
In the intravenously administered groups flumequine
was rapidly distributed to all major tissues and organs. After
oral administration flumequine
also appeared to have rapid and extensive absorption and distribution
in all 3 species. After the distribution phase, the level of
flumequine was higher in most organs and
tissues than in the blood, except in muscle and brain.
The most noticeable difference between
the species was the slow elimination of flumequine from eel
compared to turbot and halibut. In orally administered
eels, substantial amounts of flumequine
remained in all major organs/tissues for 7 d. At 28 d significant
levels of flumequine were present
in liver, kidney and skin (with traces in muscle), and at the
last sampling point (56 d) in eye, bone, bile and posterior
intestine. In orally administered turbot
significant levels of flumequine were observed over 96 h in
bile, urine, bone, skin, intestine and eye, and traces were
detected over 28 d in bone and eye in addition to a significant
level in bile. In orally administered halibut, significant
levels of flumequine were observed
in bile, skin, intestine and eye over 96 h. Traces were present
in skin and eye over 7 d. The maximal flumequine
concentrations in blood were calculated to be 2.5 mg equivalents
l(-1) (eel at 12 h), 0.8 mg l(-1) (turbot at 6 h) and 0.6 mg
l(-1) (halibut at 6 h) after oral administration.
PMID: 11804417 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11402526&dopt=Abstract
World Health Organ
Tech Rep Ser 2001;900:i-vi, 1-96
Evaluation
of certain veterinary drug residues in food.
Joint
FAO/WHO Expert Committee on Food Additives.
This report presents the conclusions of a Joint FAO/WHO Expert
Committee convened to evaluate the safety of residues of certain
veterinary drugs in food and to recommend maximum levels for
such residues in food. The first part of the report considers
the interpretation of data on inhibition of cholinesterase activity
and recommendations arising from an informal meeting on harmonization
with the Joint FAO/WHO Meeting on Pesticide Residues. A summary
follows of the Committee's evaluations of toxicological and
residue data on a variety of veterinary drugs: one anthelminthic
agent (ivermectin); four antimicrobial agents (flumequine,
lincomycin, oxytetracycline and tilmicosin); six insecticides
(cyhalothrin, cypermethrin, alpha-cypermethrin, dicyclanil,
permethrin and metrifonate (trichlorfon)); and one production
aid (melengestrol acetate). Annexed to the report are a summary
of the Committee's recommendations on these drugs, including
Acceptable Daily Intakes and Maximum Residue Limits and further
information required.
PMID: 11402526 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10705552&dopt=Abstract
Chemosphere 2000
Apr;40(7):741-50
Phytotoxicity
to and uptake of flumequine used
in intensive aquaculture on the aquatic weed, Lythrum salicaria
L.
Migliore
L, Cozzolino S, Fiori M.
Dipartimento di Biologia, Universita Tor Vergata, Roma, Italy.
luciana.migliore@uniroma2.it
Phytotoxicity of Flumequine on
the aquatic weed Lythrum salicaria L. was determined by two
laboratory models: a single concentration test, by which the
effects of 100 mg l-1 were evaluated after 10, 20, 30 days and
a multiple concentration test, by which the effects of 5000-1000-500-100-50
micrograms l-1 were evaluated after 35-day exposure. 100 mg
l-1 are highly toxic and significantly decrease the growth of
plants; this effect increases with time. Concentrations between
5000 and 50 micrograms l-1 induced hormesis in plants, by significantly
increasing mean number and dimension of leaves and secondary
roots. The effect is the highest at 50 micrograms l-1 and decreases
with increase in concentration. Both toxic effect and hormesis
can be related to plant drug uptake, quite high, in the order
of micrograms g-1. The ecological implication of Flumequine
contamination in aquatic environments and the possible use of
Lythrum salicaria for bioremediation and/or monitoring technique
are discussed.
PMID: 10705552 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10454249&dopt=Abstract
Cancer Lett 1999
Jul 1;141(1-2):99-107
Hepatotoxicity
and consequently increased cell proliferation are associated
with flumequine hepatocarcinogenesis
in mice.
Yoshida
M, Miyajima K, Shiraki K, Ando J, Kudoh K, Nakae D, Takahashi
M, Maekawa A.
Department of Pathology, Sasaki Institute, Tokyo, Japan. amaekawa@sasaki.or.jp
It has been reported that flumequine
(FLU) induces hepatic tumors in
mice when given orally for 18 months. We investigated possible
underlying mechanisms using a two-stage mouse hepatocarcinogenesis
model. After initiation with a single intraperitoneal injection
of 100 mg/kg body weight diethylnitrosamine (DEN) or saline,
male CD-1 mice were given 4000 ppm FLU
in the diet or 500 ppm phenobarbital (PB) in drinking water
for 9, 19, 24 or 30 weeks. Toxicity, evidenced
by centrilobular swollen and polar hepatocytes with fatty droplets,
infiltration of inflammatory cells and increased numbers of
mitosis in hepatocytes, was apparent in the livers of mice treated
with FLU at all time points, but its severity declined towards
the termination. FLU did
not induce cytochrome P-450 enzymes such as 1A1, 2B1 and 3A2
as assessed immunohistochemically, while positive expression
of 8-hydroxy-2'-deoxyguanosine (8-OHdG) was increased in hepatocytes
of both DEN + FLU and FLU groups
compared with the relevant controls. In animals given PB, eosinophilic
swelling of hepatocytes was prominent, and the hepatocytes showed
strongly positive reactions for CYP 1A1 and 3A2. Altered cell
foci were induced in the livers of FLU-treated
animals both with and without DEN initiation, especially the
former, and their development paralleled the degree of hepatic
toxicity. These results suggest that FLU
hepatocarcinogenicity in mice is dependent on hepatotoxic damage
and consequently increased cell proliferation. Oxidative
damage to DNA may also be a crucial factor.
PMID: 10454249 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10612037&dopt=Abstract
Eur J Pharm Biopharm
1999 Nov;48(3):253-8
Pharmacokinetics,
bioavailability and absorption of flumequine
in the rat.
Ruiz-Garcia
A, Bermejo M, Merino V, Sanchez-Castano G, Freixas J, Garrigues
TM.
Department of Pharmacy and Pharmaceutics, Faculty of Pharmacy,
University of Valencia, Spain.
The study demonstrates that the oral extent of bioavailability
of flumequine in the rat, relative
to the intravenous injection, is complete (0.94 +/- 0.04) and
not significantly different from that found by the intraduodenal
route (0.95 +/- 0.04). The rate of oral bioavailability, however,
is slow (ka = 1.20 +/- 0.07 h-1; Tmax = 2.0 h), but enough to
maintain plasma levels above the minimal inhibitory concentration
of the most common pathogens for an extended period of time
(about 10 h). The reason for the oral absorption slowness could
be a slow gastric emptying, an adsorption to the gastric mucosae,
a precipitation in the gastric medium or any other feature concerning
the stomach as the intraduodenal administration is very quick
(kid = 38.1 +/- 4.7 h-1; Tmax = 0.05 h). A possible precipitation
of flumequine cannot be discarded
as the solubility of flumequine
is very low in the pH range of 3 to 6 (mean pH values for rat
stomach and rat intestine, respectively; T.T. Kararli, Biopharm.
Drug Dispos. 16 (1995) 351-380). Flumequine
was shown to be not substantially excreted in bile (2-3% of
the dose). Surprisingly, plasma levels
and AUC values found for animals with interrupted bile flow
always surpass those found for animals with enterohepatic circulation.
This could be due to experimental model features, which might
bias plasmatic flumequine concentrations if the homeostatic
equilibrium of the animal is not completely restored due to
the volume reduction induced by biliary extraction.
PMID: 10612037 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10466502&dopt=Abstract
Vet Microbiol 1999
Jul 1;67(4):263-75
Salmonella
infections in finishing pigs in The Netherlands: bacteriological
herd prevalence, serogroup and antibiotic resistance of isolates
and risk factors for infection.
van der Wolf PJ, Bongers JH, Elbers AR,
Franssen FM, Hunneman WA, van Exsel AC, Tielen MJ.
Animal Health Service, Boxtel, The Netherlands. p.vd.wolf@gdvdieren.nl
Salmonellae are wide spread in man and animals world wide and
are of increasing significance as causative agents of foodborne
diseases in man. The European Union, national authorities and
the pig industry are therefore more and more interested in the
Salmonella status of the pig population. The aim of this study
was to estimate the bacteriological prevalence of Salmonella
in finishing pig herds, the serogroup and the resistance to
antibiotics of the isolated Salmonellae and a preliminary risk
analysis of factors associated with infection. For this, 317
finishing pig herds were randomly selected from a database containing
1500 herds in the southern part of the Netherlands. In each
herd 24 samples of fresh faeces were collected from two compartments
with pigs close to market weight. Per compartment 12 samples
of faeces were pooled into one pooled sample. Pooled samples
were cultured in duplicate. Salmonella spp. were recovered from
71 out of 306 herds (23%) in which two compartments could be
sampled. A total of 108 isolated Salmonella's were serotyped:
71 serogroup B, 3 serogroup C1, 6 serogroup C2, 22 serogroup
D1, and 6 isolates neither serogroup B, C or D1. Of a total
of 115 Salmonella isolates tested, none were resistant to colistin,
enrofloxacin, flumequin or gentamicin.
Automated liquid feeding of by-products, and membership of an
Integrated Quality Control (IQC) production group were associated
with a decreased risk of infection, while use of trough feeding
was associated with an increased risk of infection. It is necessary
to test these presumed risk factors in intervention studies
to evaluate their potency to reduce the Salmonella prevalence
in finishing pigs and thereby reduce the risk of Salmonellosis
in people consuming pork.
PMID: 10466502 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10211722&dopt=Abstract
J Vet Pharmacol Ther
1999 Feb;22(1):72-5
Excretion
of flumequine in free-swimming
Atlantic salmon (Salmo salar), determined by cannulation of
the dorsal aorta, gall bladder and urethra.
Sohlberg
S, Martinsen B, Horsberg TE, Soli NE.
Department of Pharmacology, Microbiology, and Food Hygiene,
Norwegian College of Veterinary Medicine, Oslo.
PMID: 10211722 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9828255&dopt=Abstract
Arch Environ Contam
Toxicol 1999 Jan;36(1):1-6
Algal
toxicity of antibacterial agents applied in Danish fish farming.
Lutzhoft
HH, Halling-Sorensen B, Jorgensen SE.
Section of Environmental Chemistry, Department of Analytical
and Pharmaceutical Chemistry, The Royal Danish School of Pharmacy,
Universitetsparken 2, DK-2100 Copenhagen O, Denmark.
Algal toxicity of antibacterial agents applied in fish farming
was investigated. The growth-inhibiting effects of amoxicillin
(A), flumequine (F),
oxolinic acid (OA), oxytetracycline hydrochloride (OT), sarafloxacin
hydrochloride (SF), sulfadiazine (SD), and trimethoprim (T)
were investigated by a modified test procedure based on the
procedure described in the ISO 8692 (1989) protocol on three
algal species: the freshwater cyanobacteria Microcystis aeruginosa,
the freshwater green alga Selenastrum capricornutum, and the
marine cryptophycean Rhodomonas salina. Algal growth was measured
as increased chlorophyll concentration by extraction with ethanol
followed by measurement of fluorescence. Results were quantified
in terms of growth rates using the Weibull equation to describe
the concentration response relationship. M. aeruginosa showed
higher sensitivity compared to both R. salina and S. capricornutum,
whereas the results for the latter two were more or less identical.
The toxicity (EC50 value, mg/L) in decreasing order were A (0.0037),
SF (0.015), SD (0.135), F (0.159),
OA (0.180), OT (0.207), and T (112) for M. aeruginosa; OT (1.6),
OA (10), T (16), F (18), SF (24),
SD (403), and A (3108) for R. salina; and OT (4.5), F
(5.0), SD (7.8), OA (16), SF (16), T (130), and A (NOEC >
250) for S. capricornutum. Applying this
test procedure the toxicity of antibacterial agents, being mono-
or polyprotic compounds, may be underestimated because of partitioning
between ionized and unionized forms.
PMID: 9828255 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9727328&dopt=Abstract
World Health Organ
Tech Rep Ser 1998;879:i-vi, 1-73
Evaluation
of certain veterinary drug residues in food. Forty-eighth report
of the Joint FAO/WHO Expert Committee on Food Additives.
This report
presents the conclusions of a Joint FAO/WHO Expert Committee
convened to evaluate the safety of residues of certain veterinary
drugs in foods and to recommend maximum levels for such residues
in food. The first part of the report considers standards for
the performance of studies, residues at the injection site,
and several initiatives to promote transparency of the process
for setting Maximum Residue Limits (MRLs). A summary follows
of the Committee's evaluations of toxicological and residue
data on a variety of veterinary drugs: two anthelminthic agents
(moxidectin and tiabendazole), eight antimicrobial agents (ceftiofur,
danofloxacin, dihydrostreptomycin, streptomycin, enrofloxacin,
flumequine, gentamicin and spiramycin),
one glucocorticosteroid (dexamethasone), and two insecticides
(cyfluthrin and fluazuron). Annexed
to the report are a summary of the Committee's recommendations
on these drugs, including Acceptable Daily Intakes and MRL's
and further toxicological studies and other information required.
Publication Types: Technical Report
PMID: 9727328
[PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10435345&dopt=Abstract
Analyst 1998
Dec;123(12):2789-96
Extension
of multi-residue methodology to include the determination of
quinolones in food.
Rose MD, Bygrave J, Stubbings GW.
CSL Food Science Laboratory, Colney, Norwich, UK. m.rose@csl.gov.uk
The multi-residue procedure for basic drugs described elsewhere
by this laboratory has been evaluated for quinolone and fluoroquinolone
antibiotics. The fluoroquinolones are a relatively new class
of drug and an increasing number of licensed products containing
these compounds are becoming available for use in animal husbandry.
This, along with the possibility of the development of antibiotic
resistant human pathogens, make it an important class of drug
for which methodology is required for the monitoring of residues
in food. Validation data are presented for a range of compounds
including the quinolones; oxolinic acid and nalidixic acid,
and the fluoroquinolones; flumequine,
ciprofloxacin, danofloxacin, enoxacin, enrofloxacin, lomefloxacin,
marbofloxacin, norfloxacin, ofloxacin and sarafloxacin. Foods
for which the method was validated included
poultry muscle (chicken and turkey), egg, chicken liver, honey,
cattle muscle and pig muscle. This application of the
multi-residue procedure further demonstrates the importance
and wide-ranging usefulness of the technique.
PMID: 10435345 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9280363&dopt=Abstract
J Vet Pharmacol Ther
1997 Aug;20(4):249-57
Pharmacokinetics
of flumequine in sheep after intravenous
and intramuscular administration: bioavailability and tissue
residue studies.
Delmas
JM, Chapel AM, Gaudin V, Sanders P.
CNEVA, Laboratoire des Medicaments Veterinaires, Javene, Fougeres,France.
The pharmacokinetic properties of flumequine
and its metabolite 7-hydroxyflumequine
were determined in six healthy sheep after single intramuscular
(i.m.) and intravenous (i.v) injections at a dose of 6 mg/kg
body weight. The tissue residues were determined in 20 healthy
sheep after repeated i.m. administration with a first dose of
12 mg/kg and nine doses of 6 mg/kg. The flumequine
formulation used was Flumiquil 3%
Suspension Injectable. The mean plasma concentrations of flumequine
after i.v. administration were described by a three-compartment
open model with a rapid distribution and a relatively slow elimination
phase. The low value of volume of distribution at steady state
(Vdss) (0.52 +/- 0.24 L/kg) and high value of volume of distribution
(Vdlambda3) (5.05 +/- 3.47 L/kg) emphasized the existence of
a small compartment with a slow rate of return to the central
compartment. The mean elimination half-life was 11.5 h. The
7-hydroxyflumequine plasma levels
represented 2.3% of the total area under the curve. The mean
plasma concentrations of flumequine
after i.m. administration were characteristic of a two-compartment
model with a first order absorption. The mean maximal plasma
concentration (1.83 +/- 1.15 microg/mL) was obtained rapidly,
i.e. 1.39 +/- 0.71 h after the i.m. administration. The fraction
of dose absorbed from the injection site was 85.00 +/- 30.13%.
The minimal concentrations of flumequine
during repeated treatment were significantly
lower in females than in males. Eighteen hours after
the last repeated i.m. administration, the
highest concentration of flumequine was observed at the injection
sites followed by kidney, liver, muscle and fat. The
highest concentration of 7-hydroxyflumequine
was observed in the kidney and was ten times lower than the
flumequine concentration. The longest
flumequine elimination half-life was observed in the fat.
PMID: 9280363 [PubMed - indexed for MEDLINE]
Full
article available free at http://aac.asm.org/cgi/reprint/41/9/2037.pdf
Antimicrob Agents
Chemother 1997 Sep;41(9):2037-40
Comparative
susceptibilities of various animal-pathogenic mycoplasmas to
fluoroquinolones.
Hannan
PC, Windsor GD, de Jong A, Schmeer N, Stegemann M.
Mycoplasma Experience Ltd., Reigate, Surrey, United Kingdom.
The in vitro activities of six antimicrobial agents were tested
against 162 mycoplasma strains of eight species isolated from
poultry and livestock at different geographic sites. Tiamulin
was most active (MICs at which 90% of the isolates were inhibited
[MIC90s], 0.025 to 0.25 microg/ml); enrofloxacin and danofloxacin
had near equivalent activities (MIC90s, 0.05 to 1.0 microg/ml),
but were much more active than flumequine
(MIC90s, 1 to 50 microg/ml). The MIC90s of tylosin and oxytetracycline
were 0.25 to > 100 microg/ml and 0.25 to 100 microg/ml, respectively.
PMID: 9303412 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8971675&dopt=Abstract
J Vet Pharmacol Ther
1996 Dec;19(6):460-5
Evaluation
of the dorsal aorta cannulation technique for pharmacokinetic
studies in Atlantic salmon (Salmo salar) in sea water.
Sohlberg
S, Martinsen B, Horsberg TE, Soli NE.
Department of Pharmacology, Microbiology and Food Hygiene, Norwegian
College of Veterinary Medicine, Oslo, Norway.
The antimicrobial drug flumequine
was given intravascularly and orally to cannulated and non-cannulated
Atlantic salmon (Salmo salar) in sea water at 11 degrees C.
The cannulated fish were divided into two groups, which were
given flumequine (25 mg/kg) intravenously
into the caudal vein (n = 8) and orally via a stomach tube down
the oesophagus (n = 8). After a washout period of 2 days, the
intravenously administered fish were given the drug orally,
and the orally administered fish were given the drug intravenously.
Blood samples were taken at different time points after drug
administration through a cannula inserted into the dorsal aorta.
The fish in the non-cannulated group were either given flumequine
intravenously or orally, and blood samples were collected by
killing five fish at predetermined time points after administration.
The haematocrit values were measured in all the fish daily for
4 days after drug administration and thereafter, in all the
collected blood samples throughout the whole experiment. The
haematocrit values differed significantly between the cannulated
and the non-cannulated fish. We found low haematocrit values
and slow drug elimination in the cannulated groups, compared
with higher haematocrit values and faster drug elimination in
the non-cannulated groups, but further investigations
are needed to prove any causal relations of this observation.
The volume of distribution (Vd(ss)) was twice as large in the
cannulated groups compared with the non-cannulated group, in
the fish administered the drug intravenously. In
the last part of the elimination phase, the half-lives differed
considerably between the cannulated and the non-cannulated groups
both after oral and intravenous administration. The slower
depletion of the drug concentration in the plasma of the cannulated
fish is due to the large Vd(ss) as there are only small differences
in clearance (ClT) between the groups. In
this study the elimination of flumequine in cannulated Atlantic
salmon differed from the elimination of flumequine in non-cannulated
Atlantic salmon.
Publication Types: Clinical Trial
Randomized Controlled Trial
PMID: 8971675
[PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8803876&dopt=Abstract
J Vet Pharmacol Ther
1996 Jun;19(3):184-91
Comparison
in prescribing patterns of antibacterial drugs in salmonid farming
in Norway during the periods 1980-1988 and 1989-1994.
Grave
K, Markestad A, Bangen M.
Department of Pharmacology, Norwegian College of Veterinary
Medicine, Oslo, Norway.
The choice of antibacterial drugs for
the treatment of bacterial diseases in farmed salmonids changed
dramatically during the period 1980-1994. In terms of
treatment doses, oxytetracycline chloride was the most frequently
prescribed antibacterial drug during the periods 1980-1983 and
1985-1986. In 1984, prescriptions changed in favour of furazolidone
and trimethoprim/ sulphadiazine (1:5). Oxolinic acid was introduced
for use in farmed fish in Norway in 1987, and immediately became
the drug of choice, comprising 36% and 50% of the prescribed
treatment doses in 1987 and 1988, respectively.
In 1989, flumequine was temporarily approved for use in farmed
salmonids, and during the period 1989-1994 antibacterial drug
therapy in farmed salmonids acquired the character of "mono-therapy'
with the quinolones flumequine and oxolinic acid. This
rapid change-over in the choice of drug may partly be explained
by the development of bacterial drug resistance in farmed salmonids,
both to oxytetracycline and trimethoprim/sulphadiazine. The
prescribing of furazolidone declined to zero during the study
period. The morbidity caused by bacterial infections was defined
as the number of treatment doses of antibacterial drugs per
kg biomass of farmed salmonids per year. It was estimated that
during the period 1988-1995, an average of 39% (mean value)
of farmed salmon received, in theory, an antibacterial cure
once each year. In comparison, the corresponding figure for
the period 1981-1988 was 60%. However, in 1993 this figure fell
to 13%, and declined even further in 1994 to 2.3%. The practice
of on-farm mixing of medicated feed, using prescribed raw materials
(pure drug substances) or premix formulations, declined significantly
during the period 1992-1994. This was due to the introduction,
in 1992, of new regulations on the prescribing of drugs to farmed
fish.
PMID: 8803876 [PubMed - indexed for MEDLINE]
Full
report available free at http://aac.asm.org/cgi/reprint/40/6/1504.pdf
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8726027&dopt=Abstract
Antimicrob Agents
Chemother 1996 Jun;40(6):1504-7
Resistance
to fluoroquinolones in Escherichia coli isolated from poultry.
Bazile-Pham-Khac S, Truong QC, Lafont
JP, Gutmann L, Zhou XY, Osman M, Moreau NJ.
Universite Paris VI, Laboratoire de Recherche Moleculaire sur
les Antibiotiques, France.
Quinolone-resistant Escherichia coli strains were isolated from
poultry clinical samples in Saudi Arabia. The poultry flocks
had been treated with oxolinic acid or flumequine
prophylaxis. The measure of the uptake of fluoroquinolones showed
that none of the strains had a reduced accumulation of quinolones.
The result of complementation with the wild-type E. coli gyrA
gene, which restored fluoroquinolone susceptibility, and the
isolation of DNA gyrase from six isolates indicated that the
resistant strains had an altered DNA gyrase. The minimum effective
dose of ciprofloxacin for inhibition of supercoiling catalyzed
by the isolated gyrases varied from 0.085 microgram/ml for a
susceptible isolate (MIC < 4 micrograms/ml) up to 96 micrograms/ml
for the more resistant one (strain 215, MIC > 64 micrograms/ml).
For the same two isolates, the minimum effective doses of sparfloxacin
varied from 0.17 up to 380 micrograms/ml. The in vitro selection
of spontaneous single-step fluoroquinolone-resistant mutants
using ciprofloxacin suggested that the more resistant mutants
are likely the result of several mutations. These
results also show that, as in human medicine, cross-resistance
between older quinolones and fluoroquinolones can exist in veterinary
isolates and reiterate the need for the prudent use of these
drugs.
PMID: 8726027 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8557079&dopt=Abstract
Epidemiol Infect
1995 Dec;115(3):475-83
Antibiotic
susceptibility of campylobacter isolates from sewage and poultry
abattoir drain water.
Koenraad
PM, Jacobs-Reitsma WF, Van der Laan T, Beumer RR, Rombouts FM.
Wageningen Agricultural University, Department of Food Science,
The Netherlands.
In this study, the in vitro susceptibility of 209 campylobacter
strains to the quinolones nalidixic acid, flumequine,
ciprofloxacin, enrofloxacin, and to ampicillin, tetracycline
and erythromycin was tested by the disk diffusion method. The
strains were isolated from poultry abattoir effluent (DWA) and
two sewage purification plants (SPA and SPB). Sewage purification
plant SPA received mixed sewage, including that from a poultry
abattoir, whereas SPB did not receive sewage from any meat-processing
industry. The quinolone resistance of the DWA isolates ranged
from 28% for enrofloxacin to 50% for nalidixic acid. The strains
isolated from the sewage purification plants were more susceptible
to the quinolones with a range of 11-18% quinolone resistance
for SPB isolates to 17-33% quinolone resistance for SPA isolates.
The susceptibility criteria as recommended by National Committee
Clinical Laboratory Standards (USA) cannot readily be employed
for campylobacter isolates. This investigation
shows that the resistance of campylobacter bacteria is highest
in the plant receiving sewage from a poultry slaughterhouse.
Monitoring of antibiotic resistance of aquatic Campylobacter
spp. is important, as surface waters are recognized as possible
sources of infection.
PMID: 8557079 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7482471&dopt=Abstract
Tijdschr Diergeneeskd
1995 Sep 15;120(18):531-4
[A
study of the cause of massive mortality among marine-cultured
rainbow trout (Oncorrhynchus mykiss, Walbaum) in a fish farm
in the southwestern Netherlands]
[Article in Dutch]
Oorschot RW, Booms GH, Latscha T, Boon
JH.
Vakgroep Visteelt en Visserij, Landbouwuniversiteit Wageningen.
The present study investigated the mass mortality of marine
cultured young rainbow trout (Oncorhynchus mykiss, Walbaum)
in the Netherlands. The course of the disease, the clinical
symptoms, and bacteriological and virological investigations
lead to the diagnosis: 'primary infectious pancreatic necrosis
virus (IPNV) infection followed by secondary vibriosis'. Treatment
with flumequine seemed to be effective.
The trout were possible infected with IPNV at the trout hatchery
and nursery from which they originated.
PMID: 7482471 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7590136&dopt=Abstract
Gen Pharmacol 1995
Oct;26(6):1391-5
Inhibitory
effect of flumequine, enoxacin
and norfloxacin on the GABA-induced contractile effect on the
guinea pig ileum.
Koutsoviti-Papadopoulou
M, Kounenis G, Elezoglou V.
Department of Pharmacology, Faculty of Veterinary Medicine,
Aristotelian University, Thessaloniki, Greece.
1. In the present study the effect of
flumequine, enoxacin and norfloxacin on the GABA-elicited
contractions (EC50 1.10 x 10(-5) M) on the isolated guinea pig
ileum was investigated, in a comparative manner.
2. All three fluoroquinolones dose-dependently antagonised the
GABA-induced contractions in a non-competitive manner, but no
statistical difference in the degree of the antagonism they
produced was noted. Besides, they did not influence the ileal
cholinergic contractions induced by exogenous acetylcholine.
3. These results suggest that the above
fluoroquinolones tested dose-dependently inhibit the contractile
effect of GABA on the guinea pig ileum and this inhibition seems
to be associated with an antagonistic action of the fluoroquinolones
at GABAA-receptors present in the guinea pig ileum.
PMID: 7590136 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8533292&dopt=Abstract
Vet Immunol Immunopathol
1995 Jul;47(1-2):143-52
Influence
of flumequine on in vivo mitogen
responses of European eel (Anguilla anguilla L., 1758) lymphoid
cells.
van
der Heijden MH, Booms GH, Tanck MW, Rombout JH, Boon JH.
Department of Fish Culture and Fisheries, Wageningen Agricultural
University, Netherlands.
The influence of flumequine on
mitogen induced lymphoid cell proliferation in European eels
(Anguilla anguilla L., 1758) was studied. For this purpose an
in vivo test, using peroral drug administration followed by
successive intraperitoneal injections with concanavalin A (ConA)
or bacterial lipopolysaccharides (LPS) and 5-bromo-2'-deoxyuridine,
was applied. Direct counting of proliferated cells in blood
smears revealed that flumequine possesses
mitogenic properties. A synergistic and an antagonistic
effect of the drug was observed after LPS and ConA stimulation,
respectively. Flow cytometric analysis of peripheral blood lymphoid
cells showed a significant reduction of the mean proportion
surface immunoglobulin positive cells in the flumequine-treated
animals. It is concluded that flumequine
enhances proliferation of lymphoid cells (probably surface immunoglobulin
negative cells) in eel under the present experimental conditions.
PMID: 8533292 [PubMed - indexed for MEDLINE]
Full
report available free at http://aac.asm.org/cgi/reprint/39/5/1059.pdf
Antimicrob Agents
Chemother 1995 May;39(5):1059-64
Comparative
single-dose pharmacokinetics of four quinolones, oxolinic acid,
flumequine, sarafloxacin, and enrofloxacin,
in Atlantic salmon (Salmo salar) held in seawater at 10 degrees
C.
Martinsen
B, Horsberg TE.
Department of Pharmacology, Microbiology and Food Hygiene, Norwegian
College of Veterinary Medicine, Oslo.
Quinolones are currently the most commonly
used group of antimicrobial agents in Norwegian aquaculture.
The aims of this study were to examine and compare the pharmacokinetic
properties of the quinolones oxolinic acid, flumequine,
sarafloxacin, and enrofloxacin after intravascular and oral
administration to Atlantic salmon (Salmo salar) by using identical
experimental designs. The study was performed in seawater at
10.2 +/- 0.2 degree C with Atlantic salmon weighing 240 +/-
50 g (mean +/- standard deviation). The bioavailability varied
considerably among the four quinolones. Following oral administration
of medicated feed, the bioavailabilities of oxolinic acid, flumequine,
sarafloxacin, and enrofloxacin were 30.1, 44.7,
2.2, and 55.5%, respectively. Taking the different dosages (25
mg/kg of body weight for oxolinic acid and
flumequine and 10 mg/kg for sarafloxacin and enrofloxacin)
into account, enrofloxacin showed the highest maximum concentration
in plasma, followed by flumequine,
oxolinic acid, and sarafloxacin. Following intravenous administration,
the volumes of distribution at steady state of oxolinic acid,
flumequine, sarafloxacin, and enrofloxacin
were 5.4, 3.5, 2.3, and 6.1 liters/kg,
respectively. Hence, all the quinolones showed good tissue penetration
in Atlantic salmon. The elimination half-life of three of the
quinolones, oxolinic acid, flumequine,
and sarafloxacin, was less than or equal to 24 h, with oxolinic
acid showing the shortest (18.2 h). On the other hand, the elimination
half-life of enrofloxacin was estimated to be 34.2 h, almost
twice that of oxolinic acid. This study
showed that flumequine and enrofloxacin had better pharmacokinetic
properties, compared with those of oxolinic acid, in Atlantic
salmon held in seawater.
PMID: 7625789 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7785191&dopt=Abstract
Vet Microbiol 1995
Mar;43(4):325-30
Antibioresistance
of Escherichia coli strains isolated in Morocco from chickens
with colibacillosis.
Amara
A, Ziani Z, Bouzoubaa K.
Institut Agronomique et Veterinaire Hassan II, Departement de
Pathologie Aviaire, Rabat-Instituts, Morocco.
Two hundred and fifty eight isolates of Escherichia coli were
made from autopsied chickens showing lesions of avian colibacillosis.
Antibiograms showed high levels of resistance (greater than
40%) to sulphonamides (SSS), oxytetracycline (OT), trimethoprim
+ sulphamethoxazole (STX) and chloramphenicol (C). Medium frequencies
of resistances (from 15 to 40%) were noted for streptomycin
(S), spectinomycin (SPT), nalidixic acid (NA), oxolinic acid
(OA), flumequine (UB) and enrofloxacine
(ENR). For ampicillin (AM), gentamicin (GM), nitrofurans (FT),
colistin (CS) and rifampin (RA) the frequencies of resistance
were low (less than 15%). A linked resistance was observed for
the 4 quinolones. A significant percentage of isolates (82.5%)
were resistant to at least 2 antimicrobial agents. The most
frequent antibiotypes were: C.OT.SSS.STX (4.65%), C.OT.SSS.STX.OA.NA.UB.ENR
(4.65%), AM.S.C.OT.SSS.STX (4.26%) and OT.SSS.STX (3.87%).
PMID: 7785191 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7491873&dopt=Abstract
Acta Vet Hung 1995;43(2-3):335-45
Toxicological
studies on potentiated ionophores in chickens. II. Compatibility
study.
Lehel
J, Laczay P, Mora Z, Semjen G.
Department of Pharmacology and Toxicology, University of Veterinary
Science, Budapest, Hungary.
Two trials were carried out on a total of 2 x 360 Tetra-82 broiler
chickens to study how the presence of the antioxidant duokvin
as potentiating agent influenced the compatibility of reduced
doses of monensin (12.5 mg/kg of feed) or maduramicin (3.0 mg/kg
of feed) with other chemotherapeutic agents (tiamulin, erythromycin,
sulfaquinoxaline, sulfachlorpyrazine, flumequine,
tylosin, kitasamycin) widely used in broiler
rearing. Compatibility was assessed on the basis of the
appearance of clinical signs suggestive of toxic interaction,
the mortality rate, body mass gain, feed consumption and drinking
water intake, and changes in AST and LDH activities of the blood
plasma. The monensin-duokvin combination (12.5 mg monensin/kg
of feed + 120 mg duokvin/kg of feed) was found to be compatible
with erythromycin, sulfaquinoxaline, sulfachlorpyrazine, flumequine,
tylosin and kitasamycin. For tiamulin, a slight incompatibility
was observed; however, this was much less severe than that found
for monensin administered at a dose of 100 mg/kg of feed. The
maduramicin-duokvin combination (3.0 mg maduramicin/kg of feed
+ 120 mg duokvin/kg of feed) was compatible with all the compounds
tested; thus, it can be safely applied also in combination with
tiamulin.
PMID: 7491873 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7740745&dopt=Abstract
Vet Q 1994
Dec;16(4):206-8
In
vitro susceptibility of Campylobacter and Salmonella isolates
from broilers to quinolones, ampicillin, tetracycline, and erythromycin.
Jacobs-Reitsma
WF, Koenraad PM, Bolder NM, Mulder RW.
Institute for Animal Science and Health (ID-DLO), Branch Beekbergen,
The Netherlands.
Recently, an increased resistance of Campylobacter to fluoroquinolones,
a newer class of antimicrobial agents in both human and veterinary
medicine, has been reported. Campylobacter isolates (617) from
150 broiler flocks were tested for their susceptibility to cephalothin
(control), ampicillin, tetracycline, erythromycin, and the quinolones
nalidixic acid, flumequine, enrofloxacin,
and ciprofloxacin by a disc diffusion method. Almost complete
cross-resistance was found between the quinolones tested. Campylobacter
isolates (181, 29%), originating from 55 flocks (37%), were
quinolone resistant. Salmonella isolates (94) from 40 flocks
were also tested for their antimicrobial susceptibility. Eight
isolates (8.5%), from three broiler flocks (7.5%), showed resistance
to nalidixic acid and flumequine
(and tetracycline), but not to ciprofloxacin or enrofloxacin.
PMID: 7740745 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7871699&dopt=Abstract
Vet Q 1994
Oct;16(3):152-6
Establishment
of a microbiologically acceptable daily intake of antimicrobial
drug residues.
Nouws
JF, Kuiper H, van Klingeren B, Kruyswijk PG.
RIKILT-DLO, Wageningen, The Netherlands.
A model is presented to calculate the microbiologically acceptable
daily intake (ADIm) of antibiotic residues in food products.
The ADIm calculation is based on MIC values for indicator bacteria
Escherichia coli, Bacteroides fragilis, Bifidobacterium spp.
and Eubacterium spp., established under gut-like conditions
in an in vitro simulation model. The maximum residue level (MRL)
for residues in food products can be derived from the ADIm.
Four phases can be distinguished in this gastro-intestinal simulation
model, namely:
1. In vitro determination of the MIC for each bacterial strain
by a standard method.
2. Incorporation of the drug into food (meat, milk) followed
by testing of the stability of the antibiotic under gut-like
conditions.
3. Adjustment of the 'gastric' fluid to the duodenal situation,
inoculation with the test bacteria and anaerobic incubation
at 37 degrees C for at least 18 h. 4. MIC reading confirmed
by counting bacteria growing on specific solidified media. In
this study the method for calculation of ADIm and MRL is given
for flumequine as model drug. On
the basis of MIC50 values for E. coli strains, a MRL for flumequine
of 1.0 microgram/g meat or 0.25 microgram/ml milk was calculated.
It is suggested that, depending on the antibacterial spectrum
of the antibiotic involved, the ADIm can be determined with
selected indicator bacteria, incubated under simulated gastrointestinal
conditions.
PMID: 7871699 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9747335&dopt=Abstract
Zhonghua
Min Guo Wei Sheng Wu Ji Mian Yi Xue Za Zhi 1994
May;27(2):70-9
Susceptibility
of avian mycoplasmas isolated in Taiwan to 21 antimicrobial
agents.
Lin MY, Chiang YC, Lin KY, Sung HT.
Department of Veterinary Medicine, National Pingtung Polytechnic
Institute, Taiwan, Republic of China.
Twenty-one antimicrobial agents were incorporated individually
into Frey's agar to evaluate their inhibitory activities against
86 isolates of avian mycoplasmas recently detected in Taiwan.
Among them, 45 and 37 isolates were found positive with Mycoplasma
gallisepticum and Mycoplasma synoviae fluorescent antibody conjugate,
respectively. Twenty-one other isolates were unable to be identified
by the above 2 conjugates. All of the field isolates were highly
sensitive (with MIC50 < 1 microgram/ml) to enrofloxacin,
gentamicin, myplabin, tiamutin and tylosin. However, those field
isolates were highly resistant (with MIC50 > 32 micrograms/ml)
to apramycin, chlortetracycline (CTC), erythromycin (ER), flumequine
(FI), nalidixic acid (NA), oxolinic acid (OA), oxytetracycline
(OTC) and spiramycin (SP). The inhibitory activities of the
antibiotics which possessed an MIC90 of 50 micrograms/ml or
less against local isolates were, in decreasing order, enrofloxacin
(< 0.004 microgram/ml), gentamicin (1.53 micrograms/ml),
tiamutin (1.81 micrograms/ml), tylosin (3.2 micrograms/ml),
streptomycin (SM; 12.0 micrograms/ml), colistin (13.1 micrograms/ml),
chloramphenicol (14.0 micrograms/ml), spectinomycin (15.0 micrograms/ml),
myplabin (16.0 micrograms/ml), spiramycin (30.0 micrograms/ml),
minocycline (32.0 micrograms/ml). The MIC90 of OA, CTC, SM,
FI, SP, OTC, ER or NA was greater than 50 micrograms/ml; which
work poorly in the control of mycoplasmoses. Since
the antibiotic control policy is quite loose in Taiwan, many
antimicrobial agents are often freely used in clinics, with
a resulting gradual decrease in the inhibitory activity to the
avian mycoplasmas.
PMID: 9747335 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8079154&dopt=Abstract
Sci Total
Environ 1994 Aug 2;152(2):143-52
Effects
of antibacterial agents on transformation of fatty acids in
sediment from a marine fish farm site.
Johnsen
RI.
Department of Chemistry, University of Bergen, Norway.
The conversion of fatty acids in marine fish farm sediment from
a simulated abandoned site was investigated. Five containers
of aquaculture sediment were followed in 1 year. Antibacterial
agents: oxytetracycline, flumequine
and oxolinic acid, respectively, were added to three of the
containers, while two were controls. The fatty acid composition
in the sediment was examined by direct methanolysis on sediment,
high-resolution gas chromatography and multivariate data-analysis.
The total amount of fatty acids decreased strongly in all containers
and the fatty acid profile in the sediment changed clearly towards
the profile of natural, unaffected sediment with time. During
the experimental period, the added drugs
had a retarding effect on the transformation of fatty acids
in the sediment. This effect, however, was not detectable
after 10 months.
PMID: 8079154 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8017208&dopt=Abstract
Acta Pharm
Hung 1994 Mar;64(2):51-6
[Development
and investigation of preparations containing kitasamycin and
flumequine]
[Article in
Hungarian]
Kata M, Vilimszky Z, Dombi G, Varga J.
SZOTE Gyogyszertechnologiai Intezet, Szeged, Eotvos.
Swine dysentery and poultry cholera are very harmful animal
diseases which cause great damage. Flumequine
and kitasamycin are new and up-to-date preparations for the
treatment of these diseases. ++ Imequyl ad us. vet. and ++ Trubin
ad us. vet. are the registered medicines. The doses are 7
mg flumequine and 21 mg kitasamycin/body weight kg. The
drug technological problem is that flumequine
does not dissolve sufficiently in water. It dissolves
well at pH = 10, but kitasamycin is unstable at this pH. It
was hoped that these two components would together act as agonists,
and that kitasamycin would promote the dissolution of flumequine.
An injection preparation and a powder mixture for dissolution
were developed. Chemical interaction between the components
was conformed by IR and NMR measurements.
PMID:
8017208 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8196100&dopt=Abstract
J Vet Pharmacol
Ther 1994 Feb;17(1):80-2
Glucuronidation
of flumequine by the turtle Pseudemys
scripta elegans.
Vree TB, Hoeben UM, van Ewijk-Beneken
Kolmer EW, Nouws JF.
Department of Clinical Pharmacy, Academic Hospital Sint Radboud,
Nijmegen, The Netherlands.
PMID: 8196100 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7847199&dopt=Abstract
Acta Vet
Scand 1994;35(3):299-301
Effect
of cooking on residues of the quinolones oxolinic acid and flumequine
in fish.
Steffenak I, Hormazabal V, Yndestad M.
Department of Food Hygiene, Norwegian College of Veterinary
Medicine, Oslo.
The effect of cooking on residues of the quinolones oxolinic
acid and flumequine in fish was
investigated. Salmon containing residues of oxolinic acid and
flumequine was boiled or baked
in the oven. Samples of raw and cooked muscle, skin, and bone,
as well as of the water in which the fish was boiled and juice
from the baked fish, were analysed. Oxolinic acid and flumequine
did not degrade at the temperatures reached when cooking the
fish. However, fish muscle free from drug residues may be contaminated
during boiling and baking due to leakage of the drug from reservoirs
in the fish.
PMID: 7847199 [PubMed
- indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8360830&dopt=Abstract
J Pharm
Sci 1993 May;82(5):518-20
Extraction
and analysis by high-performance liquid chromatography of antibiotics
in a drug delivery system for farmed fish.
Rogstad
A, Weng B.
Apothekernes Laboratorium, Oslo, Norway.
Simple assays for extraction and determination of the concentrations
of the antibiotics oxytetracycline, oxolinic acid, and flumequine
in a drug dosage form for farmed fish are described.
HPLC with UV detection was used in the analyses. The recovery
of all three drugs was approximately 100%, and the precision
varied from 0.5-3.0%. The methods are applicable to the production
control, quality control, and stability control of the products.
PMID: 8360830 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1299991&dopt=Abstract
Therapie
1992 Sep-Oct;47(5):440
[Anaphylactic
shock induced by flumequine]
[Article in
French]
Pinzani V, Gennaro G, Petit P, Blayac
JP.
Publication Types: Letter
PMID: 1299991
[PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1447340&dopt=Abstract
J Chromatogr
1992 Aug 7;579(1):131-41
Direct-gradient
high-performance liquid chromatographic analysis and preliminary
pharmacokinetics of flumequine and flumequine
acyl glucuronide in humans: effect of probenecid.
Vree
TB, van Ewijk-Beneken Kolmer EW, Nouws JF.
Department of Clinical Pharmacy, Sint Radboud Hospital, University
of Nijmegen, Netherlands.
A gradient high-performance liquid chromatographic analysis
for the direct measurement of flumequine,
with its acyl glucuronide, in plasma and urine of humans has
been developed. In order to prevent hydrolysis and isomerization
of flumequine acyl glucuronide,
the samples were acidified by the oral intake of four 1.2-g
amounts of ammonium chloride per day. In contrast to the acyl
glucuronides of non-steroidal anti-inflammatory drugs, flumequine
and its acyl glucuronide were stable in urine of pH 5.0-8.0.
Flumequine acyl glucuronide is
unstable at pH 1.5. In acidic urine (pH 5-6), almost no flumequine
is excreted unchanged (1%): it is excreted chiefly as acyl glucuronide
(84.2%). Probenecid co-medication reduces the renal excretion
rate of flumequine acyl glucuronide
from 662 to 447 micrograms/min (p = 0.00080), but not the percentage
of glucuronidation.
PMID: 1447340 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1810198&dopt=Abstract
Antimicrob
Agents Chemother 1991 Dec;35(12):2634-5
In
vitro susceptibility of the fish pathogen Aeromonas salmonicida
to flumequine.
Barnes
AC, Lewin CS, Hastings TS, Amyes SG.
Department of Medical Microbiology, University of Edinburgh
Medical School, United Kingdom.
The activity of the fluoroquinolone flumequine
was investigated against the fish pathogen Aeromonas salmonicida
and was compared with that of oxolinic acid. Flumequine
was more active than oxolinic acid in terms of its MIC against
oxolinic acid-resistant isolates of A. salmonicida and was as
active as oxolinic acid against susceptible isolates. In contrast
to oxolinic acid, flumequine was
bactericidal, with only 1% of the bacteria surviving 6 h of
exposure to the drug at concentrations slightly above the MIC.
Mutation to resistance to flumequine
was found to occur at a lower frequency than that to oxolinic
acid. Hence, in vitro, flumequine
appears to possess some advantages over oxolinic acid against
this fish pathogen.
PMID: 1810198 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1666873&dopt=Abstract
Encephale
1991 Nov-Dec;17(6):511-4
[Neuropsychiatric
manifestations and quinolones. Apropos of a case]
[Article in
French]
Rampa S, Caroli F.
l'Hopital Sainte-Anne, Paris.
The authors specified, briefly, the different subgroups and
prevalence of the molecules from the quinolone family: Nalidixic
acid (synthesised in 1958), the quinolones of second generation
(oxilinic acid, piromidique, pipemidique and flumequine)
and the quinolones of third generation (ciprofloxacine, norfloxacine,
ofloxacine, perfloxacine). After having mentioned the extent
and the importance of using these antibiotics in infections,
they stressed the fact that the quinolones are antibiotics which
are largely prescribed in clinics and hospitals. The authors
reported afterwards the observation of a young female, without
any precedent neuropsychiatric disorders having shown a complex
clinical state with neurological and psychiatric disturbances
during the first day of treatment for a urinary infection with
4 tablets of flumequine 400 mg
per day (instead of 3 recommended). Mrs. A. 25 years of age
was seen to during the night at The "Consultation Psychiatrique
d'Orientation et d'Accueil" (C.P.O.A.). of Sainte-Anne
hospital by the resident psychiatric of a General Hospital "after
behavioural disturbances". In fact, about 3 hours before
and 15 minutes after the third dose of flumequine
(2 tablets of 400 mg), this makes the total dose taken over
12 hours is equal to 400 x 4 = 1,600 mg, the patient developed
an intense discomfort with blurred vision accompanied by nausea,
followed by a state of restlessness and incomprehensible speech.
A testimony by relatives revealed that she suffered, shortly
afterwards, a generalised fit which affected her 4 limbs with
a fixation of her eyes and hypersalivation and convulsions without
either swallowing the tongue or involuntary urination.(ABSTRACT
TRUNCATED AT 250 WORDS)
PMID: 1666873 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2135062&dopt=Abstract
J Toxicol
Clin Exp 1990 Nov-Dec;10(7-8):469-72
[Acute
psychiatric syndrome and quinolones]
[Article in
French]
Defoin JF, Debonne T, Rambourg MO, Seraphin
J, Buffet M, Jaussaud M, Bertault R, Fay R, Digeon B.
SAMU 51/Centre Anti-Poisons-Service du Docteur G.A. SEYS-C.H.R.U.
Reims.
A case of Flumequine poisoning
is described; a 13-year-old girl was admitted for a psychiatric
syndrome. 3 hours after, seizures, coma,
and metabolic disorders were observed. Infectious, encephalitic
or diabetic diseases were suspected, but not confirmed. After
12 hours of a symptomatic treatment, the clinical status improved
and the patient was discharged. At that time a tablet was found
in her bedroom and a mas spectrographic analysis was positive
for Flumequine. This case report
is in agreement with previous observations and confirms the
small therapeutic index of quinolone, and the absolute necessity
to assess carefully a psychiatric diagnosis.
PMID: 2135062 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2124211&dopt=Abstract
J Antimicrob
Chemother 1990 Oct;26 Suppl B:219-25
Central
nervous system toxicity of quinolones: human and animal findings.
Christ W.
Institut fur Arzneimittel des Bundesgesundheitsamtes, Berlin,
FRG.
Quinolones have been reported to induce CNS reactions in 0.9-2.1%
of cases, but severe reactions occur in less than 0.5%. Flumequine
and fleroxacin, but not other quinolones, have produced convulsions
in animals after systemic administration; by interventricular
injection convulsions could be produced by some quinolones,
but by pefloxacin only when a dose of 400 micrograms was reached.
A possible mechanism for CNS excitation may be the displacement
of GABA from receptors. Quinolones may interact with other drugs--theophylline,
caffeine, non-steroidal anti-inflammatory drugs--in producing
CNS effects.
PMID: 2124211 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1964964&dopt=Abstract
J Pharm
Belg 1990 Sep-Oct;45(5):299-305
[Photophysical
evaluation of photosensitization by various quinolones]
[Article in
French]
Vermeersch G, Filali A, Marko J, Catteau
JP, Couture A.
Laboratoire de Physique, Faculte de Pharmacie, UA CNRS 351,
Universite de Lille II, France.
An original physicochemical method is proposed for the evaluation
of the photosensitizing activity of drugs in vitro. A Nuclear
Magnetic Resonance (NMR) spectrum is recorded during light irradiation
of drug solutions. The change in the intensity of the NMR lines
under such conditions is termed the Photochemically Induced
Dynamic Nuclear Polarization (Photo-CIDNP) effect. It is related
to the formation of radical intermediates which may be involved
in the in vivo photosensitization reactions (the so-called type-I
photoreactions). Nine commercial quinolones were tested by this
method: nalidixic, oxolinic, pipemidic and piromidic acids,
rosoxacin, flumequine, enoxacin,
pefloxacin and norfloxacin. Each quinolone was irradiated in
alcoholic solutions in its UV absorption band (300-350 nm) in
the absence or in the presence of a biological target chosen
as a model: the amino-acid N-acetyltyrosine. The quinolones
were classified in two groups in relation to the intensities
of the observed CIDNP effects. Nalidixic and oxolinic acids,
rosoxacin and flumequine are among the
most potent photosensitizers.
PMID: 1964964 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2384907&dopt=Abstract
J Vet Pharmacol
Ther 1990 Jun;13(2):159-69
Pharmacokinetics,
metabolism and renal clearance of flumequine
in veal calves.
Mevius
DJ, Breukink HJ, Guelen PJ, Jansen T, De Greve B.
Department of Large Animal Medicine and Nutrition, Veterinary
Faculty, State University of Utrecht, The Netherlands.
The pharmacokinetics of flumequine
was studied in 1-, 5- and 18-week-old veal calves. A two-compartment
model was used to fit the plasma concentration-time curve of
flumequine after the intravenous
injection of 10 mg/kg of a 10% solution. The elimination half-life
(t1/2 beta) of the drug ranged from 6 to 7 h. The Vd beta and
ClB of 1-week-old calves (1.07 l/kg, 1.78 ml/min/kg) were significantly
lower than those of 5-week-old (1.89 l/kg, 3.23 ml/min/kg) and
18-week-old calves (1.57 l/kg, 3.10 ml/min/kg). After the oral
administration of 10 mg/kg of a 2% flumequine
formulation mixed with milk replacer, the Cmax was highest in
1-week-old (9.27 micrograms/ml) and lowest in 18-week-old calves
(4.47 micrograms/ml). The absorption was rapid (Tmax of approximately
3 h) and complete. When flumequine
itself and a formulation containing 2% flumequine
and 20 X 10(6) iu of colistin sulphate were mixed with milk
replacer and administered at the same dose rate, absorption
was incomplete and Cmax was lower. The main urinary metabolite
of flumequine was the glucuronide
conjugate (approximately 40% recovery within 48 h of intravenous
injection) and the second most important metabolite was 7-hydroxy-flumequine
(approximately 3% recovery within 12 h of intravenous injection).
Only 3.2-6.5% was excreted in the urine unchanged. After oral
administration a 'first-pass' effect was observed, with a significant
increase in the excretion of conjugated drug. For 1-week-old
calves it is recommended that the 2% formulation should be administered
at a dose rate of 8 mg/kg every 24 h or 4 mg/kg every 12 h;
for calves over 6 weeks old, the dose should be increased to
15 mg/kg every 24 h or 7.5 mg/kg every 12 h. The formulation
containing colistin sulphate should be administered to 1-week-old
calves at a flumequine dose of
12 mg/kg every 24 h or 6 mg/kg every 12 h.
PMID: 2384907 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2080842&dopt=Abstract
Ann Rech
Vet 1990;21 Suppl 1:137S-144S
Pharmacokinetic
and residue studies of quinolone compounds and olaquindox in
poultry.
Anadon
A, Martinez-Larranaga MR, Diaz MJ, Velez C, Bringas P.
Department of Pharmacology, Institute of Pharmacology and Toxicology,
CSIC, Faculty of Medicine, Complutense University, Madrid, Spain.
Nalidixic acid and similar antimicrobial agents have been available
for more than 20 years, mainly for treating infections caused
by Gram-negative enterobacteria. Recently, several chemically
related drugs, including oxolinic acid, pipemidic acid, piromidic
acid and flumequine, have been
developed. They are either naphthyridine-carboxylic acid or
quinoline-carboxylic acid derivatives and, with nalidixic acid,
are so-called quinolones. A major advance in antimicrobial chemotherapy
was the synthesis of newer quinolones
containing at least 1 fluorine atom and a piperazinyl
group. These new fluoroquinolones have an extended antimicrobial
spectrum compared to the first quinolone generation, and are
highly active against most Gram-negative pathogens including
the Enterobacteriaceae and Pseudomonas aeruginosa. The pharmacokinetic
properties and residue levels of these quinolones and fluoroquinolones
for which clinical experience or experimental information exists
in poultry are reviewed here. On the other hand, administration
of the quinoxaline-di-N-oxide, olaquindox, for medical purposes
raises questions concerning the pharmacokinetic disposition
of the drug and the risk of its residues in poultry. This paper
presents information about the pharmacokinetic profile of olaquindox
and the presence of its residues in chickens.
Publication Types: Review
Review, Tutorial
PMID: 2080842
[PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2603356&dopt=Abstract
Vet Q 1989
Oct;11(4):232-41
Oral
absorption and bioavailability of flumequine
in veal calves.
Mevius
DJ, Breukink HJ, Jansen T, Guelen PJ, de Greve B.
Department of Large Animal Medicine and Nutrition, Faculty of
Veterinary Medicine, Utrecht, The Netherlands.
The oral absorption and bioavailability of flumequine
was studied in 1-, 5- and 18-week-old calves following intravenous
and oral administration of different formulations of flumequine
(Flumix, Flumix C and pure flumequine).
Increasing age had a negative influence on the Cmax after the
administration of Flumix, based on a larger VD in the older
calves. The Cmax decreased from 5.02 +/- 1.46 micrograms/ml
in the first week to 3.28 +/- 0.42 micrograms/ml in the 18th
week. Adding colistin sulfate to the flumequine
formulation and administring pure flumequine
mixed with milk replacer had a negative effect on the Cmax of
flumequine after oral administration
of 5 and 10 mg/kg body weight. The bioavailability of the orally
administered flumequine formulations
was 100% in all cases except after the administration of Flumix
C, for which it was 75.9 +/- 18.2%. The urinary recovery of
flumequine after intravenous injection
of a 10% solution varied from 35.2 +/- 2.3% for Group B, to
41.2 +/- 6.3% for Group C. The dosage of 5 mg/kg body weight
Flumix twice daily in 1-week-old veal calves is sufficient to
reach therapeutic plasma concentrations, based on a MIC value
of 0.8 micrograms/ml of the target bacteria. In older calves
it is advisable to increase the dosage 7.5 or 10 mg/kg body
weight every 12 hours. In combination with colistin sulfate
it is also advisable to increase the dosage slightly because
of the negative effect of the colistin sulfate on the Cmax of
flumequine.
PMID: 2603356 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3606076&dopt=Abstract
Antimicrob
Agents Chemother 1987 May;31(5):768-73
4-Quinolone
drugs affect cell cycle progression and function of human lymphocytes
in vitro.
Forsgren
A, Schlossman SF, Tedder TF.
Most antibacterial agents do not affect human lymphocyte function,
but a few are inhibitory. In contrast, a pronounced increase
in the incorporation of [3H]thymidine in the presence of 4-quinolones
was observed in these studies. The uptake of [3H]thymidine into
DNA (trichloroacetic acid precipitable) was significantly increased
in phytohemagglutinin-stimulated human lymphocytes when they
were exposed to eight new 4-quinolone derivatives, ciprofloxacin,
norfloxacin, ofloxacin, A-56619, A-56620, amifloxacin, enoxacin,
and pefloxacin, at 1.6 to 6.25 micrograms/ml for 5 days. Four
less antibacterially active 4-quinolones (nalidixic acid, cinoxacin,
flumequine, and pipemidic acid)
stimulated [3H]thymidine incorporation only at higher concentrations
or not at all. Kinetic studies showed that incorporation
of [3H]thymidine was not affected or slightly inhibited by ciprofloxacin
2 days after phytohemagglutinin stimulation but was increased
on days 3 to 6. The total incorporation of [3H]thymidine from
day 1 to day 6 after phytohemagglutinin stimulation was increased
by 42 to 45% at 5 to 20 micrograms of ciprofloxacin per ml.
Increased [3H]thymidine incorporation was also seen when human
lymphocytes were stimulated with mitogens other than phytohemagglutinin.
Ciprofloxacin added at the start of the culture had a more pronounced
effect on [3H]thymidine incorporation than when added later.
In spite of the apparent increase in DNA synthesis, lymphocyte
growth was inhibited by 20 micrograms of ciprofloxacin per ml,
and cell cycle analysis showed that ciprofloxacin inhibited
progression through the cell cycle.(ABSTRACT TRUNCATED AT 250
WORDS)
PMID: 3606076 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2932714&dopt=Abstract
Presse Med
1985 Sep 21;14(31):1668
[Massive
flumequine poisoning]
[Article in
French]
Boles JM, Gentric A, Garre M, Cochard
G, Pernez C, Scheydecker JL.
Publication Types: Letter
PMID: 2932714
[PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2932732&dopt=Abstract
Presse Med
1985 Sep 28;14(32):1712
[A
case of anaphylactic shock induced by flumequine]
[Article in
French]
Marsepoil T, Blin F, Lo JM, Horel D'Ancona
F, Sebbah JL.
Publication Types: Letter
PMID: 2932732
[PubMed - indexed for MEDLINE]
1984 - Order Number:
NTIS/MIC-90-00046, 11p
Flumequine distribution and tissue
kinetics in rainbow trout Salmo gairdneri Richardson: Detection
of residues.
Chevalier R, Gerard JP, Michel C
Canada Inst. for Scientific and Technical Information, Ottawa
(Ontario).
An earlier study demonstrated the value of flumequine in treating
furunculosis in salmonids and the absence of any signs of acute
toxicity in the subjects treated. Toxicity is an important factor
in assessing potential risks for the consumer as a result of
residues that may be present in the fish. The purpose of this
study was to detect flumequine residues in rainbow trout 6,
12, 24, 48, 72, and 96 hours after cessation of a 5-day treatment
with 6 or 12 mg/kg/day. Canadian translation of fisheries and
aquatic sciences no. 5116. Translated from French. Originally
published in French.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6840466&dopt=Abstract
Gastroenterol
Clin Biol 1983 Feb;7(2):217-8
[Immunoallergic
hepatitis induced by flumequine]
[Article in French]
Dubois A, Janbon C, Pignodel C, Marty-Double
C.
Publication Types: Letter
PMID: 6840466
[PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6672059&dopt=Abstract
J Fr Ophtalmol
1983;6(10):829-36
[Serous
macular detachment of the neuro-epithelium and flumequine]
[Article in French]
Sirbat D, Saudax E, Hurault de Ligny B,
Hachet E, Raspiller A.
Flumequine (1 200 mg/day) was prescribed
as treatment for infection of the urinary tract to three patients
with chronic renal failure, who reported positive scotoma three
days later. Ophthalmologic examination evinced bilateral symmetrical
macular bullae. A characteristic yellow papule was present at
foveal level. In all three cases, visual acuity was impaired
(down to 4/10), without any angiographic alteration. Foveolas
showed a moderate persistent hyperfluorescence. All patients
recovered a normal visual acuity, within two days after treatment
cessation, and bullae disappeared without sequelae within 5
days. The chronology and kinetics of clinical manifestations
were clearly and reproducibly correlated with flumequine
therapy in all patients, and suggest that this drug may be considered
responsible for the ocular symptom reported. Chronic renal failure
(creatinine clearance lower than 25 ml/mn) most certainly favoured
the appearance of visual troubles, but other factors may possibly
play a similar role: hepatic failure, individual hypersensitivity...
Quinolones used as urinary antiseptics (nalidixic acid, oxolinic
acid, pipemidic acid...), and other flumequine
analogues may possibly be involved in such side-effects. This
was reported by Bouissou et al. in an experimental model with
nalidixic acid, where transient bullae appeared on young animals'
articular cartilage. Such lesions are related to focal alterations
of the C2 intermediary layer of cartilage, with marked edema
of the interstitial material. The volume of synovial fluid increases
concomitantly. These alterations suggest a direct cytotoxic
effect at the intercellular level of target organs, a mechanism
possibly also occurring in the retina.
PMID: 6672059 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6660786&dopt=Abstract
Ann Dermatol
Venereol 1983;110(9):765
[Photo-onycholysis
caused by Apurone]
[Article in French]
Revuz J, Pouget F.
PMID: 6660786 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6139048&dopt=Abstract
Ann Biol
Clin (Paris) 1983;41(4):239-49
[Detection
and diagnosis of drug induced lithiasis]
[Article in
French]
Daudon M, Protat MF, Reveillaud RJ.
Drug-induced calculi are often mis-diagnosed because of inadequate
analysis of the urinary calculi. These stones can only be characterized
unambiguously by global physical methods like infra-red spectrophotometry.
From a series of 2,000 calculi analysed under infra-red, we
identified 22, i.e. 1.1% of cases, which contained, partly or
entirely, drug products. Ten other cases are still being studied.
Amongst the products identified we found metabolites of glafenine
(Glifanan) in 7 cases, triamterene and its derivatives (Cycloteriam)
in 7 cases, metabolites of phenazopyridine (Pyridium) in 4 cases,
sulphonamides in 2 cases : N-acetylsulphamethoxazole hydrochloride
(Bactrim) and N-acetylsulphaguanidine (Guanidan), flumequine
(Apurone) in 1 case and calcite (Cal-Mag-Na) in 1 case.
The authors estimate that about 100,000 calculi are excreted
in France each year and that at least 1,000 of these potentially
contain drugs and are not diagnosed. Early recognition of drug
induced stones is essential in order to protect the patient
from recurrences, the risks of renal complications or, more
simply, from useless therapeutic or dietetic regimes.
PMID: 6139048 [PubMed - indexed for MEDLINE]
FAN
Note: Definition of Lithiasis: the formation of stones (calculi)
in an internal organ, eg: Cholelithiasis is the presence of
gallstones in the gallbladder; Enterolithiasis is the presence
of calculi in the intenstines; Nephrolithiasis is the presence
of kidney stones (calculi) in the kidney. Ref: http://dictionary.metor.com/wnet/4051724.htm
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7135332&dopt=Abstract
Therapie
1982 Jul-Aug;37(4):481-7
[Neurologic
side effects of quinolones]
[Article in French]
Galland MC, Jouve-Bestagne MH, Rodor F,
Jouglard J.
PMID: 7135332 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=340442&dopt=Abstract
J Antimicrob
Chemother 1977 Nov;3(6):615-20
Biovaluation
of the antibacterial flumequine
for enteric use.
Rohlfing SR, Gerster JF, Kvam DC.
PMID: 340442 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=984753&dopt=Abstract
Antimicrob
Agents Chemother 1976 Jul;10(1):20-4
Bioevaluation
of the antibacterial flumequine
for urinary tract use.
Rohlfing SR, Gerster JR, Kvam DC.
PMID: 984753 [PubMed - indexed for MEDLINE]
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