Traynor, N. J., M.D. Barratt, W.W. Lovell, J. Ferguson, and N.K. Gibbs. Comparison of an In Vitro Cellular Phototoxicity Model Against Controlled Clinical Trials of Fluoroquinolone Skin Phototoxicity. 2000.Toxicol. in Vitro 14: 275-283.[Reprinted with permission from Elsevier Science]

ciprofloxacin - 85721-33-1; grepafloxacin - 119914-60-2; lomefloxacin - 98079-51-7; norfloxacin - 70458-96-7; ofloxacin - 82419-36-1; trovafloxacin - 147059-72-1

Many therapeutic drugs induce phototxic skin responses following exposure to solar or artificial ultraviolet radiation sources. Several in vitro model systems have been developed to predict drug phototoxicity but none have been conducted in parallel with controlled clinical phototoxicity studies on systemically administered pharmaceuticals. The in vitro phototoxicity of eight fluoroquinolone (FQ) antibiotics (ciprofloxacin, grepafloxacin, lomefloxacin, norfloxacin, ofloxacin, trovafloxacin, BAYy3118, moxifloxacin) was determined by exposing Chinese hamster fibroblasts to UVA radiation. Cell damage was quantified with standard MTT or neutral red assays and an in vitro phototoxic index calculated (PIvit=% cell viability with UVA alone/% cell viability with UVA + FQ) for each endpoint. Clinical photosensitising ability of the eight systemically administered FQ was investigated using double-blind, placebo and positive controlled, clnical skin phototesting of normal subjects. Minimal erythema doses at 365 plus/minus 30 nm were determined before and after 6-7 days of FQ ingestion and PIclin (minimal erythema dose without FQ/minimal erythema dose with FQ) calculated. Linear regression analysis of PIvit vs. PIclin gave correlations of up to 0.893. Principal components analysis of PIvit, daily dose, plasma levels and photophysical (absorption) properties of the eight FQ showed that phototoxic (arbitrarily defined as PIclin greater than or equal to 2) and non-phototoxic (PIclin less than 2) FQ could be completely discriminated using these parameters, and that the in vitro models were able to rank the relative phototoxic potential of the eight FQ.