Drug-induced phototoxicity; an early in vitro identification of phototoxic potential of new drug entities in drug discovery and development.
Drug-induced photoirritation can be defined as an inflammatory reaction of the skin after topical or systemic administration of pharmaceutical substances. In many cases of drug-induced phototoxicity, skin reactions can be triggered by doses of sunlight regarded as harmless and most often in the ultraviolet A (320-400 nm). Several classes of drugs including antibacterials, thiazide diuretics, non-steroidal anti-inflammatory drugs, quinolones, and tricyclic antidepressants, even though nontoxic by themselves, may become reactive under exposure to environmental light, leading to undesired side effects. At least three types of drug-induced phototoxic skin reactions, including the photoirritant, photogenotoxic and photoallergic skin responses, have been recognized, and their mechanisms and pathologic features are quite different. The development of effective methodology to evaluate the photochemical/biological properties has been attempted over the past few years, since it would be a key consideration to predict and avoid the phototoxic risk in the early phase of the drug discovery process. The aim of this review is to describe the clinical features, pathogenesis and photochemical characteristics of drug-induced phototoxicity, and the current developments in research tools for predicting phototoxic potential of new drug entities are also addressed.
Department of Pharmacokinetics and Pharmacodynamics and Global Center of Excellence (COE) Program, School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka 422-8526, Japan. onoue@u-shizuoka-ken.ac.jp
Satomi
S
Onoue
Yoshiki
Y
Seto
Graham
G
Gandy
Shizuo
S
Yamada
D017454:Dermatitis, Photoallergic / Q000209:etiology*; D017484:Dermatitis, Phototoxic / Q000209:etiology*; D055808:Drug Discovery; D064420:Drug-Related Side Effects and Adverse Reactions; D006801:Humans; D008027:Light; D018570:Risk Assessment; D014466:Ultraviolet Rays / Q000009:adverse effects*