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

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...

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Bibliographic Details
Published in:Toxicology in vitro 2000-06, Vol.14 (3), p.275-283
Main Authors: Traynor, N.J., Barratt, M.D., Lovell, W.W., Ferguson, J., Gibbs, N.K.
Format: Article
Language:English
Subjects:
Animals
Anti-Infective Agents - toxicity
Biological and medical sciences
Cells, Cultured
clinical
Cricetinae
Cricetulus
Dermatitis, Phototoxic - etiology
Double-Blind Method
Drug toxicity and drugs side effects treatment
fluoroquinolone
Fluoroquinolones
Humans
in vitro
Medical sciences
MTT
neutral red
Pharmacology. Drug treatments
phototesting
phototoxocity
Toxicity: skin, dermoskeleton
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Summary: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±30 nm 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
ISSN:0887-2333
1879-3177
DOI:10.1016/S0887-2333(00)00017-5