Demonstration of Quinolone Phototoxicity in vitro

Abstract

The ‘first-generation’ quinolones cinoxacin, nalidixic acid, oxolinic acid, pipemidic acid and rosoxacin and the newly developed quinolones ciprofloxacin, enoxacin, fleroxacin, norfloxacin and ofloxacin were screened in vitro at 10^––⁵,10^––4 and 10^––3M concentrations for ultraviolet (UV)-induced phototoxic effects in a photohemolysis test. At 10^––3 M, photodependent effects of norfloxacin could not be evaluated, as hemolysis occurred without irradiation. All other compounds with the exception of ciprofloxacin were found to be phototoxic at 10^-3 M and some also at 10^-4M. Hemolysis was UV dose dependent and for all compounds most prominent after exposure to UVA-rich radiation except for fleroxacin which was most active in the UVB range. Besides fleroxacin, also oxolinic acid, pipemidic acid and rosoxacin induced hemolysis with irradiations rich in UVB. It is concluded that quinolones have to be regarded as potentially phototoxic substances. Therefore intense light exposure should be avoided during treatment with these agents.

Evaluation of Phototoxic Properties of Fragrances

“…Thus, although the photohaemolysis test does not allow disclosure of effects related to DNA damage, phototoxicity demonstrated in this system supports photocarcinogenetic risks. This is not surprising, as besides DNA damage, other mechanisms also contribute to UV-induced skin cancer (5,28,29,30).…”

Privileged Structures - Dream or Reality: Preferential Organization of Azanaphthalene Scaffold

“…This drug because of its poor pharmacokinetics, relatively high active concentration and narrow spectrum of activity is mainly used in the treatment of bacterial infections of the urinary tract [198,199]. Nevertheless, the research on nalidixic acid derivatives has led to a new era of fluoroquinolones [200]. Derivatization with fluoride at the C6 position of the quinoline skeleton resulted in the development of the second generation of quinolone antibiotics (Fig.…”

Drug-induced phototoxicity evoked by inhibition of human ABC transporter ABCG2: development ofin vitrohigh-speed screening systems

“…In addition, UVA-enhanced photocarcinogenesis was reported in hairless mice [14] . Pipemidic acid, oxolinic acid, and rosoxacin belong to this first generation of quinolones, and demonstrate similar photosensitizing properties [15] . Among these quinolones the most frequently reported photosensitive effects included systemic, often bullous, phototoxic eruptions; porphyria cutanea tarda; and pseudoporphyria.…”

“…Fluoroquinolone photosensitivity is mainly exerted by UVA, with the exception of fleroxacin, which is most active in vitro in the UVB range [15,22] . A synergistic effect of UVB and UVA has been documented in the case of sparfloxacininduced phototoxic ear-swelling response in mice [23] .…”