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

N. J. Traynor, M. D. Barratt, W. W. Lovell, J. Ferguson, N. K. Gibbs

    Research output: Contribution to journalArticlepeer-review

    Abstract

    Many therapeutic drugs induce phototoxic 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 (PI(vit)=% 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, clinical skin phototesting of normal subjects. Minimal erythema doses at 365±30nm were determined before and after 6-7 days of FQ ingestion and PI(clin) (minimal erythema dose without FQ / minimal erythema dose with FQ) calculated. Linear regression analysis of PI(vit) vs PI(clin) gave correlations of up to 0.893. Principal components analysis of PI(vit), daily dose, plasma levels and photophysical (absorption) properties of the eight FQ showed that phototoxic (arbitrarily defined as PI(clin) ≥ 2) and non-phototoxic (PI(clin) <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. Copyright (C) 2000 Elsevier Science Ltd.
    Original languageEnglish
    Pages (from-to)275-283
    Number of pages8
    JournalToxicology in Vitro
    Volume14
    Issue number3
    DOIs
    Publication statusPublished - Jun 2000

    Keywords

    • Clinical
    • Fluoroquinolone
    • In vitro
    • MTT
    • Neutral red
    • Phototesting
    • Phototoxocity

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