CHARACTERIZATION OF CUTANEOUS PHOTOTOXICITY INDUCED BY TOPICAL ALPHA-TERTHIENYL AND ULTRAVIOLET-A RADIATION

[摘要] Alpha-terthienyl (.alpha.-T), a phototoxic thiophene compound isolated from marigolds (Tagetes species), affects cell membranes and does not appear to induce cytogenetic damage. This study was undertaken to investigate topical delivery of .alpha.-T and characterize its cutaneous phototoxicity in combination with long-wave UV radiation (UVA) in comparison with locally (intradermal) administered .alpha.-T. Percutaneous penetration (PC) of 0.1% and 1% .alpha.-T in a 3% Azone gel vehicle was studied in guinea pig skin in vitro and quantitated by UV fluorescence microscopy. Dose-dependent PC of epidermis, adnexae, and superficial dermis was demonstrated in vitro. Alpha-terthienyl (0.1% and 1%) in this vehicle was applied topically in vivo and irradiated with 30 J/cm2 UVA at intervals of 10 min-24 h. Maximum sensitization was acheived with irradiation 1 h following drug application. The clinical response was dose-dependent consisting of erythema, edema, crusting, erosion, and inhibition of hair growth and was observed 72 h to 7 days postirradiation. A comparable dose-dependent phototoxic response was observed when 5-500 .mu.g .alpha.-T were injected intradermally and irradiated with UVA. These results indicated that low-dose topical .alpha.-T in a nonirritating vehicle can rapidly produce cutaneous photosensitization. Topical .alpha.-T/UVA may provide a selective and safer alternative approach for the photochemotherapy of psoriasis and other cutaneous diseases.

[发布日期] 1986-09-01