Comparison of an in vitro cellular phototoxicity model against controlled clinical trials of fluoroquinolone skin phototoxicity

Many therapeutic dregs induce phototoxic skin responses following exposure to solar or artificial ultraviolet radiation sources. Several in vitro mode l systems have been developed to predict drug phototoxicity but none have b een conducted in parallel with controlled clinical phototoxicity studies on systemically administered pharmaceuticals. The in vitro phototoxicity of e ight fluoroquinolone (FQ) antibiotics (ciprofloxacin, grepafloxacin, lomefl oxacin, norflxacin, ofloxacin, trovafloxacin, BAYy3118, moxifloxacin) was d etermined by exposing Chinese hamster fibroblasts to UVA radiation. Cell da mage was quantified with standard MTT or neutral red assays and an in vitro phototoxic index calculated (PIvit = % cell viability with UVA alone+% cel l viability with UVA + FQ) for each endpoint, Clinical photosensitising abi lity of the eight systemically administered FQ was investigated using doubl e-blind, placebo and positive controlled, clinical skin phototesting of nor mal subjects. Minimal erythema doses at 365 +/- 30 nm were determined befor e and after 6-7 days of FQ ingestion and PI,li, (minimal erythema dose with out FQ + minimal erythema dose with FQ) calculated. Linear regression analy sis of PIvit vs PIelin gave correlations of up to 0.893. Principal componen ts analysis of PIvit, daily dose, plasma levels and photophysical (absorpti on) properties of the eight FQ showed that phototoxic (arbitrarily defined as PIelin greater than or equal to 2) and non-phototoxic (PIclin, < 2) FQ c ould be completely discriminated using these parameters, and that the in vi tro models were able to rank the relative phototoxic potential of the eight FQ. (C) 2000 Elsevier Science Ltd All rights reserved.