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Abstracts

KEYWORDS:
photocarcinogenic, photocarcinogenicity
photoclastogenic
photocytotoxic
photogenotoxic
photohemolytic
photomutagenic, photomutagenicity
phototoxic, phototoxicity

Name:	Gemifloxacin
CAS No.	175463-14-6 (and 204519-64-2)
Formula:	C18-H20-F-N5-O4
Structure:
Other Names:	LB-20304 SB 265805
Class	Fluoroquinolone
Effects (some, not all)	• Photoclastogenic • Phototoxic
Use:	Antibiotic used to treat infections such as pneumonia (lung infections) or bronchitis (infection of the tubes moving air in and out of the lungs) caused by certain bacteria.

Gemifloxacin Abstracts:

The photochemical clastogenic potential of 12 quinolone antibacterial agents with or without light irradiation was assessed by an in vitro chromosomal aberration test using cultured CHL cells. Exposure to all test compounds, except for DK-507k, increased the incidence of cells with structural aberrations excluding gap (TA) following light irradiation. Test compounds used in the present study under light irradiation were divided into three groups based on their ED50 values, doses inducing chromosomal aberrations in 50% of cells. The first group with ED50 values below 30 g/ml includes sparfloxacin (SPFX), clinafloxacin (CLFX), gemifloxacin (GMFX), lomefloxacin (LFLX), sitafloxacin (STFX), grepafloxacin (GPFX) and fleroxacin (FLRX); the second group with ED50 values of 100 g/ml, enoxacin (ENX) and levofloxacin (LVFX); the third group with little or no potency, moxifloxacin (MFLX), trovafloxacin (TVFX) and DK-507k. The photochemical clastogenicity of these compounds correlates well with their reported in vivo phototoxic potentials. In the chemical structure and clastogenicity relationships, substitution of a methoxy group at the C-8 position in the quinolone nucleus was confirmed to reduce not only photochemical clastogenicity, but also the clastogenic potential of quinolone antibacterial agents.
Ref: In vitro photochemical clastogenicity of quinolone antibacterial agents studied by a chromosomal aberration test with light irradiation. By Satoru Itoh et al. Mutation Research/Genetic Toxicology and Environmental Mutagenesis Volume 517, Issues 1-2 , 27 May 2002, Pages 113-121.

Name:	Grepafloxacin
CAS No.	119914-60-2
Formula:	C19-H22-F-N3-O3
Structure:
Other Names	CCRIS 7284 GPFX
Class	Fluoroquinolone
Effects (some, not all)	• Photogenotoxic   • Photoclastogenic     • Phototoxic  • Can prolong the QT interval to cause lethal ventricular arrhythmias
Use:	Antibacterial Drug / Therapeutic Agent • Withdrawn from worldwide markets due to cardiovascular effects

Grepafloxacin Abstracts:

Fluoroquinolone development from 1985 to the present was reviewed. Severe drug adverse events were noted for enoxacin, pefloxacin and fleroxacin, which were phototoxic. Temafloxacin was associated with severe hemolytic-uremic syndrome, lomefloxacin caused phototoxicity and central nervous system (CNS) effects, and sparfloxacin was associated with phototoxicity and QTc prolongation. Tosufloxacin caused severe thrombocytopenia and nephritis, and hepatotoxicity was reported for trovafloxacin. Grepafloxacin was withdrawn due to cardiovascular effects, and clinafloxacin was associated with phototoxicity and hypoglycaemia. The structure of the quinolones directly relates to both their activity and side-effect profiles. The relationship among specific substituents attached to the quinolone nucleus are clarified. The incidence of specific adverse events associated with individual fluoroquinolones was reviewed in a five-year post-marketing surveillance (PMS) study in Japan, in which a total adverse drug reaction (ADR) rate of 1.3% was found for levofloxacin, compared to total ADR rates of 3.3% for pazufloxacin, 3.6% for tosufloxacin, 4.5% for gatifloxacin and 5.4% for balofloxacin. Gastrointestinal effects were the most common adverse events for all fluoroquinolones. Levofloxacin had the lowest rate of CNS effects and skin adverse events among the agents listed.
Ref: History of quinolones and their side effects by E Rubinstein. Chemotherapy. 2001;47 Suppl 3:3-8; discussion 44-8.

Clinical trials in patients with community- and hospital-acquired infections have established that the clinical effectiveness and safety of fluoroquinolones are similar to -lactam and macrolide agents. The most common drug-related adverse effects (AEs) with fluoroquinolone therapy involve the gastrointestinal troct and central nervous system and are usually transient and mild to moderate in severity. However, serious toxic reactions have led to the limited and restrictive use of trovafloxacin in the United States and the withdrawal of temafloxacin and grepafloxacin from worldwide markets. In addition, postmarketing spontaneous AE reports have imposed updates in the precautions and warning sections of product package inserts of selected fluoroquinolones. This article reviews the AEs associated with the fluoroquinolones and compares the safety profiles of ciprofloxacin, levofloxacin, gatifloxacin, and moxifloxacin.
Ref: Safety and tolerability of fluoroquinolones; by Kelly A. Sprandel PharmD and Keith A. Rocivold PharmD, FCP, FCCP. Clinical Cornerstone Volume 5, Supplement 3 , 2003, Pages S29-S36

Recent reports on the photochemical carcinogenicity and photochemical genotoxicity of fluoroquinolone antibacterials led to an increasing awareness for the need of a standard approach to test for photochemical genotoxicity. In this study the micronucleus test using V79 cells was adapted to photogenotoxicity testing. Results of using different UVA/UVB relationships enabled us to identify a suitable irradiation regimen for the activation of different kinds of photosensitizers. Using this regimen, 8-methoxypsoralen and the fluoroquinolones lomefloxacin, grepafloxacin and Bay Y 3118 were identified to cause micronuclei and toxicity upon photochemical activation.
Ref: The application of the micronucleus test in Chinese hamster V79 cells to detect drug-induced photogenotoxicity. By B Kersten et al. Mutat Res 1999 Sep 15;445(1):55-71.

The photochemical clastogenic potential of 12 quinolone antibacterial agents with or without light irradiation was assessed by an in vitro chromosomal aberration test using cultured CHL cells. Exposure to all test compounds, except for DK-507k, increased the incidence of cells with structural aberrations excluding gap (TA) following light irradiation. Test compounds used in the present study under light irradiation were divided into three groups based on their ED50 values, doses inducing chromosomal aberrations in 50% of cells. The first group with ED50 values below 30 g/ml includes sparfloxacin (SPFX), clinafloxacin (CLFX), gemifloxacin (GMFX), lomefloxacin (LFLX), sitafloxacin (STFX), grepafloxacin (GPFX) and fleroxacin (FLRX); the second group with ED50 values of 100 g/ml, enoxacin (ENX) and levofloxacin (LVFX); the third group with little or no potency, moxifloxacin (MFLX), trovafloxacin (TVFX) and DK-507k. The photochemical clastogenicity of these compounds correlates well with their reported in vivo phototoxic potentials. In the chemical structure and clastogenicity relationships, substitution of a methoxy group at the C-8 position in the quinolone nucleus was confirmed to reduce not only photochemical clastogenicity, but also the clastogenic potential of quinolone antibacterial agents.
Ref: In vitro photochemical clastogenicity of quinolone antibacterial agents studied by a chromosomal aberration test with light irradiation. By Satoru Itoh et al. Mutation Research/Genetic Toxicology and Environmental Mutagenesis Volume 517, Issues 1-2 , 27 May 2002, Pages 113-121.

Grepafloxacin (GPFX), a newly synthesized antibacterial agent, was administered orally to pregnant Std:NZW rabbits at daily doses of 20, 40 and 60 mg/kg during the organogenetic period, and the effects on dams and fetuses were examined. 1) Dams in the 40 mg/kg or higher dose groups revealed death, abortion, decreased spontaneous motor activity, suppression of body weight gain, and decreased food consumption. These changes were remarkable in the 60 mg/kg dose group...
Ref: [Reproductive and developmental toxicity studies of grepafloxacin (3) -- teratogenicity study in rabbits by oral administration]. By H Uchiyama et al. Yakuri To Chiryo 1994;22(11):41-8.

Grepafloxacin (GPFX), a newly synthesized antibacterial agent, was administered orally to pregnant Slc:SD rats during the organogenetic period at daily doses of 20, 50 and 150 mg/kg, and the effects on dams, fetuses and offspring were examined. 1) On dams, body weight gain was suppressed in the 150 mg/kg dose group, and food consumption decreased in the 50 mg/kg and higher dose groups during the gestational period... Necropsy findings showed enlarged cecum in the 50 mg/kg and higher dose groups. ... 2) Decreases in the number of fetal ossified sacrococcygeal vertebrae and in placental weight in the 150 mg/kg dose group was observed...
Ref: [Reproductive and developmental toxicity studies of grepafloxacin (2) -- teratogenicity study in rats by oral administration]. By H Uchiyama et al. Yakuri To Chiryo 1994;22(11):25-39.

Excerpts: Since noncardiovascular drug-induced prolongation of the QT interval is often associated with the onset of torsades de pointes resulting in life-threatening ventricular arrhythmias (De Ponti et al., 2001; Haverkamp et al., 2000 and Tamargo, 2000), worldwide regulatory authorities have raised a heightened awareness on the submission of data surrounding the ventricular repolarization process. Moreover, general nonclinical testing strategy for delayed ventricular repolarization by human pharmaceuticals is being discussed in draft stage guideline ICH S7B for safety pharmacology studies (The ICH Steering Committee, 2002).
In the case of fluoroquinolone antibacterial agents, it has been reported that sparfloxacin and grepafloxacin can prolong the QT interval to cause lethal ventricular arrhythmias (Bertino and Fish, 2000; Demolis et al., 1996; Dupont et al., 1996 and Owens, 2001), which were withdrawn in most countries. Recently, gatifloxacin and moxifloxacin were developed as third generation of fluoroquinolones (Ball, 2000). However, in vitro studies have indicated that gatifloxacin and moxifloxacin markedly prolonged the action potential duration of the isolated guinea pig ventricular myocardium and canine Purkinje fibers (Gintant et al., 2001; Hagiwara et al., 2001 and Patmore et al., 2000). Also, gatifloxacin and moxifloxacin inhibited the human cardiac repolarizing K+ current (Anderson et al., 2001; Bischoff et al., 2000 and Kang et al., 2001). Clinical studies on the safety pharmacology of gatifloxacin and moxifloxacin indicated that these fluoroquinolones may induce QT prolongation and ventricular arrhythmias (Bertino et al., 2002; Démolis et al., 2000; Iannini and Circiumaru, 2001; Noel et al., 2003; Siepmann and Kirch, 2001 and Von Keutz and Schlüter, 1999).
Ref: In vivo experimental approach for the risk assessment of fluoroquinolone antibacterial agents-induced long QT syndrome; by Katsuyoshi Chiba et al. European Journal of Pharmacology Volume 486, Issue 2 , 20 February 2004, Pages 189-200.

The new fluoroquinolones (clinafloxacin, gatifloxacin, gemifloxacin, grepafloxacin, levofloxacin, moxifloxacin, sitafloxacin, sparfloxacin and trovafloxacin) offer excellent activity against Gram-negative bacilli and improved Gram-positive activity (e.g. against Streptococcus pneumoniae and Staphylococcus aureus) over ciprofloxacin... Several of these agents have either been withdrawn from the market, had their use severely restricted because of adverse effects (clinafloxacin because of phototoxicity and hypoglycaemia; grepafloxacin because of prolongation of the QTc and resultant torsades de pointes; sparfloxacin because of phototoxicity; and trovafloxacin because of hepatotoxicity), or were discontinued during developmental phases. The remaining fluoroquinolones such as gatifloxacin, gemifloxacin, levofloxacin and moxifloxacin have adverse effect profiles similar to ciprofloxacin. Extensive post-marketing safety surveillance data (as are available with ciprofloxacin and levofloxacin) are required for all new fluoroquinolones before safety can be definitively established. Drug interactions are limited; however, all fluoroquinolones interact with metal ion containing drugs (eg. antacids)..
Ref: A critical review of the fluoroquinolones: focus on respiratory infections; by GG Zhanel et al. Drugs. 2002;62(1):13-59.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=11790155

Name:	Levofloxacin
CAS No.	100986-85-4
Formula:	C18-H20-F-N3-O4
Structure:
Other Names	(S)-Ofloxacin CCRIS 4074 DR3355 DRG-0129 Elequine HR 355 Iquix Ofloxacin S-(-)-form RWJ 25213-097
Class	Fluoroquinolone
Effects (some, not all)	• Photogenotoxic • Photoclastogenic • Phototoxic • Diminished healing during the early stages of fracture repair; may compromise fracture healing in humans.
Use:	Drug / Therapeutic Agent

Levofloxacin Abstracts:

AIM: To compare two methods of measuring DNA damage induced by photogenotoxicity of fluoroquinolones (FQ).
METHODS: Lomefloxacin (LFLX), sparfloxacin (SPFX), ciprofloxacin (CPFX), and levofloxacin (LELX) were tested by comet assay and photodynamic DNA strand breaking activity under the different conditions of UVA irradiation.
RESULTS: In comet assay, photogenotoxicity was evident at SPFX 1 mg/L, LFLX 5 mg/L, and CPFX 5 mg/L, and LELX 10 mg/L. In photodynamic DNA strand-breaking activity, SPFX and LFLX induced the conversion of the supercoiled form into the nicked relaxed form at 10-50 micromol/L, while CPFX at 25 micromol/L and LELX at 50 micromol/L.
CONCLUSION: There were good correlations between the two methods to detect DNA damage induced by phototoxicity of fluoroquinolones. Photodynamic DNA strand breaking activity was a good method to detect DNA damage induced by photogenotoxicity of fluoroquinolones as well as comet assay.
Ref: Compare two methods of measuring DNA damage induced by photogenotoxicity of fluoroquinolones. By Zhang T, Li JL, Xin J, Ma XC, Tu ZH. Acta Pharmacol Sin. 2004 Feb;25(2):171-5.

The photochemical clastogenic potential of 12 quinolone antibacterial agents with or without light irradiation was assessed by an in vitro chromosomal aberration test using cultured CHL cells. Exposure to all test compounds, except for DK-507k, increased the incidence of cells with structural aberrations excluding gap (TA) following light irradiation. Test compounds used in the present study under light irradiation were divided into three groups based on their ED50 values, doses inducing chromosomal aberrations in 50% of cells. The first group with ED50 values below 30 g/ml includes sparfloxacin (SPFX), clinafloxacin (CLFX), gemifloxacin (GMFX), lomefloxacin (LFLX), sitafloxacin (STFX), grepafloxacin (GPFX) and fleroxacin (FLRX); the second group with ED50 values of 100 g/ml, enoxacin (ENX) and levofloxacin (LVFX); the third group with little or no potency, moxifloxacin (MFLX), trovafloxacin (TVFX) and DK-507k. The photochemical clastogenicity of these compounds correlates well with their reported in vivo phototoxic potentials. In the chemical structure and clastogenicity relationships, substitution of a methoxy group at the C-8 position in the quinolone nucleus was confirmed to reduce not only photochemical clastogenicity, but also the clastogenic potential of quinolone antibacterial agents.
Ref: In vitro photochemical clastogenicity of quinolone antibacterial agents studied by a chromosomal aberration test with light irradiation. By Satoru Itoh et al. Mutation Research/Genetic Toxicology and Environmental Mutagenesis Volume 517, Issues 1-2 , 27 May 2002, Pages 113-121.

We previously have shown that experimental fractures exposed to ciprofloxacin have diminished fracture healing. The purpose of this study was to assess the effect of levofloxacin and trovafloxacin on experimental fracture healing to test the hypothesis that diminished fracture healing is a quinolone class effect. Sixty-one male Wistar rats were divided into three groups, which received 25 mg/kg of levofloxacin twice daily for 3 weeks, 35 mg/kg of trovafloxacin twice daily for 3 weeks, or no treatment, beginning 7 days after production of closed, nondisplaced, bilateral femoral fractures. The mean peak serum concentrations of levofloxacin and trovafloxacin drawn 30 minutes after administration were 6.9 and 7.0 microg/mL, respectively. Radiographic, histologic, and biomechanical studies were used to evaluate fracture healing. Torsional strength testing of fracture callus exposed to levofloxacin and trovafloxacin revealed a decrease in strength (299 and 257 N-mm, respectively) as compared with controls (364 N-mm). Radiographs revealed significantly more advanced healing in control animals (Goldberg score of 2.1) compared with the fractures in the rats treated with levofloxacin and trovafloxacin (Goldberg score of 1.5 in both groups). Fracture calluses in the animals treated with levofloxacin and trovafloxacin showed a lower histologic grade (5.3 and 3.5, respectively) as compared with control animals (7.5) representing a less mature callus with the presence of more cartilage and less woven bone. These data suggest that experimental fractures systemically exposed to levofloxacin or trovafloxacin have diminished healing during the early stages of fracture repair. The administration of quinolones during early fracture repair may compromise fracture healing in humans.
Ref: Levofloxacin and trovafloxacin inhibition of experimental fracture-healing; by AC Perry et al. Clin Orthop Relat Res. 2003 Sep;(414):95-100.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=12966282

This paper focuses on the development of four major adverse drug reactions (ADRs) associated with some fluoroquinolones: convulsions, phototoxicity, cardiac effects, and hepatotoxicity. CNS adverse events have been linked to fluoroquinolone administration, including seizures, which are more likely with co-administration of NSAIDs. Only 61 cases of convulsions have been reported with levofloxacin, with 33 of those affected having received NSAIDs. The assumed rate of serious convulsions was as low as 1/65,000 with NSAIDs and 1/260,000 without NSAIDs. Levofloxacin has a very low phototoxicity-inducing potential confirmed by pre-clinical animal studies and the results of post-marketing surveillance (PMS). Pre-clinical results demonstrated that levofloxacin was 20 times less phototoxic than sparfloxacin and PMS data show that serious phototoxicity develops in only 1 in 1.8 million cases treated with levofloxacin. While many fluoroquinolones are associated with cardiac effects, pre-clinical data has shown that compared with sparfloxacin and grepafloxacin, levofloxacin has no effect on myocardial conduction. PMS data further support the safety of levofloxacin in this regard. While trovafloxacin is associated with serious hepatic problems, PMS data demonstrates that levofloxacin has a very low incidence of 1/100,000 hepatic effects. These results were confirmed in a prospective study that confirmed a low 1.3% incidence rate for all ADRs associated with levofloxacin.
Ref: Latest industry information on the safety profile of levofloxacin in Japan by K Yagawa (Daiichi Pharmaceutical Co). Chemotherapy. 2001;47 Suppl 3:38-43; discussion 44-8.

Name:	Lomefloxacin
CAS No.	98079-51-7
Formula:	C17-H17-Cl-F-N3-O3
Structure:
Other Names	BRN 4210041 CCRIS 6305 DM-10 Lomefloxacin Lomefloxacine [French] Lomefloxacino [Spanish] Lomefloxacinum [Latin] SC 47111A
Class	Fluoroquinolone
Effects (some, not all)	• Photogenotoxic • Photocarcinogenic  • Photoclastogenic • Central nervous system effects
Use:	Antibacterial Antitubercular agents Drug / Therapeutic Agent

Lomefloxacin Abstracts:

Fluoroquinolone development from 1985 to the present was reviewed. Severe drug adverse events were noted for enoxacin, pefloxacin and fleroxacin, which were phototoxic. Temafloxacin was associated with severe hemolytic-uremic syndrome, lomefloxacin caused phototoxicity and central nervous system (CNS) effects, and sparfloxacin was associated with phototoxicity and QTc prolongation. Tosufloxacin caused severe thrombocytopenia and nephritis, and hepatotoxicity was reported for trovafloxacin. Grepafloxacin was withdrawn due to cardiovascular effects, and clinafloxacin was associated with phototoxicity and hypoglycaemia. The structure of the quinolones directly relates to both their activity and side-effect profiles. The relationship among specific substituents attached to the quinolone nucleus are clarified. The incidence of specific adverse events associated with individual fluoroquinolones was reviewed in a five-year post-marketing surveillance (PMS) study in Japan, in which a total adverse drug reaction (ADR) rate of 1.3% was found for levofloxacin, compared to total ADR rates of 3.3% for pazufloxacin, 3.6% for tosufloxacin, 4.5% for gatifloxacin and 5.4% for balofloxacin. Gastrointestinal effects were the most common adverse events for all fluoroquinolones. Levofloxacin had the lowest rate of CNS effects and skin adverse events among the agents listed.
Ref: History of quinolones and their side effects by E Rubinstein. Chemotherapy. 2001;47 Suppl 3:3-8; discussion 44-8.

AIM: To compare two methods of measuring DNA damage induced by photogenotoxicity of fluoroquinolones (FQ).
METHODS: Lomefloxacin (LFLX), sparfloxacin (SPFX), ciprofloxacin (CPFX), and levofloxacin (LELX) were tested by comet assay and photodynamic DNA strand breaking activity under the different conditions of UVA irradiation.
RESULTS: In comet assay, photogenotoxicity was evident at SPFX 1 mg/L, LFLX 5 mg/L, and CPFX 5 mg/L, and LELX 10 mg/L. In photodynamic DNA strand-breaking activity, SPFX and LFLX induced the conversion of the supercoiled form into the nicked relaxed form at 10-50 micromol/L, while CPFX at 25 micromol/L and LELX at 50 micromol/L.
CONCLUSION: There were good correlations between the two methods to detect DNA damage induced by phototoxicity of fluoroquinolones. Photodynamic DNA strand breaking activity was a good method to detect DNA damage induced by photogenotoxicity of fluoroquinolones as well as comet assay.
Ref: Compare two methods of measuring DNA damage induced by photogenotoxicity of fluoroquinolones. By Zhang T, Li JL, Xin J, Ma XC, Tu ZH. Acta Pharmacol Sin. 2004 Feb;25(2):171-5.

Recent reports on the photochemical carcinogenicity and photochemical genotoxicity of fluoroquinolone antibacterials led to an increasing awareness for the need of a standard approach to test for photochemical genotoxicity. In this study the micronucleus test using V79 cells was adapted to photogenotoxicity testing. Results of using different UVA/UVB relationships enabled us to identify a suitable irradiation regimen for the activation of different kinds of photosensitizers. Using this regimen, 8-methoxypsoralen and the fluoroquinolones lomefloxacin, grepafloxacin and Bay Y 3118 were identified to cause micronuclei and toxicity upon photochemical activation.
Ref: The application of the micronucleus test in Chinese hamster V79 cells to detect drug-induced photogenotoxicity; by B Kersten et al. Mutat Res 1999 Sep 15;445(1):55-71.

The phototoxic potential of eight fluoroquinolones (norfloxacin, ofloxacin, enoxacin, ciprofloxacin, lomefloxacin, tosufloxacin, sparfloxacin and gatifloxacin) was evaluated by using three in vitro methods of cytotoxicity against mammalian cells, erythrocyte lysis and DNA strand breakage. All fluoroquinolones tested with the exception of gatifloxacin, an 8-methoxy quinolone, showed DNA strand breaking activities under UV-A irradiation. Their cytotoxicity against HeLa cells was also enhanced by UV-A irradiation. In particular, the phototoxic potential of sparfloxacin, enoxacin and lomefloxacin was high in both methods. Ofloxacin is very photocytotoxic against HeLa cells, while it has low potential to cause DNA strand breakage. Norfloxacin, ciprofloxacin and enoxacin were very photohemolytic, but sparfloxacin was not, indicating that the in vivo phototoxic potencies of fluoroquinolones might not be predictable by the photohemolysis study. Gatifloxacin, a non-phototoxic quinolone, showed no phototoxic potential in any of these three in vitro tests. These results suggest that determination of DNA strand breaking activity, combined with cytotoxicity against mammalian cells, is available to predict the phototoxic potential of fluoroquinolones without laboratory animals.
Ref: In vitro method for prediction of the phototoxic potentials of fluoroquinolones; by T. Yamamoto et al. Toxicology in Vitro - Volume 15, Issue 6 , December 2001, Pages 721-727.

... Fluoroquinolones (FQ) are a relatively new class of antibacterials that are useful in the treatment of gram-negative bacterial infections. When used in humans FQ's often cause phototoxicity. Recent studies have shown that lomefloxacin and fleroxacin cause squamous cell carcinomas in hairless mice injected with these drugs and irradiated with UV-A (315-400) nm. We have studied the photochemical properties of lomefloxacin and related FQ's to determine why these drugs as a class are phototoxic and why lomefloxacin and fleroxacin are photocarcinogenic. Singlet oxygen (1O2) and superoxide yields for the FQ antimicrobials do not correlate with their phototoxic potentials. However, photocleavage of pBR322 DNA by the FQ antibiotics is at least 10-fold more efficient for difluorinated quinolones (lomefloxcin and fleroxacin) than for monofluorinated analogs. 1O2 does not induce photocleavage. Futhermore, the inhibitory effect of O2 on the induction of frank strand breaks makes it unlikely that superoxide could play a major role in the photocleavage of DNA by these antibiotics. We have now found that upon UVA-irradiation the F-8 fluorine atoms of lomefloxacin and fleroxacin are lost as fluoride with the concomitant generation of a carbene at C-8. In contrast non-photocarcinogenic FLQ's norfloxacin and ciprofloxacin did not exhibit UVA-induced fluoride loss...
Ref: MECHANISMS OF CHEMICALLY INDUCED PHOTOSENSITIVITY by CF CHIGNELL. 1997 - Crisp Data Base National Institutes of Health. Document Number: CRISP/98/ES50046-19.

The photochemical clastogenic potential of 12 quinolone antibacterial agents with or without light irradiation was assessed by an in vitro chromosomal aberration test using cultured CHL cells. Exposure to all test compounds, except for DK-507k, increased the incidence of cells with structural aberrations excluding gap (TA) following light irradiation. Test compounds used in the present study under light irradiation were divided into three groups based on their ED50 values, doses inducing chromosomal aberrations in 50% of cells. The first group with ED50 values below 30 g/ml includes sparfloxacin (SPFX), clinafloxacin (CLFX), gemifloxacin (GMFX), lomefloxacin (LFLX), sitafloxacin (STFX), grepafloxacin (GPFX) and fleroxacin (FLRX); the second group with ED50 values of 100 g/ml, enoxacin (ENX) and levofloxacin (LVFX); the third group with little or no potency, moxifloxacin (MFLX), trovafloxacin (TVFX) and DK-507k. The photochemical clastogenicity of these compounds correlates well with their reported in vivo phototoxic potentials. In the chemical structure and clastogenicity relationships, substitution of a methoxy group at the C-8 position in the quinolone nucleus was confirmed to reduce not only photochemical clastogenicity, but also the clastogenic potential of quinolone antibacterial agents.
Ref: In vitro photochemical clastogenicity of quinolone antibacterial agents studied by a chromosomal aberration test with light irradiation. By Satoru Itoh et al. Mutation Research/Genetic Toxicology and Environmental Mutagenesis Volume 517, Issues 1-2 , 27 May 2002, Pages 113-121.