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Characterization of cutaneous phototoxicity induced by topical alpha-terthienyl and ultraviolet a radiation

  • Author(s): Rampone, WM
  • McCullough, JL
  • Weinstein, GD
  • Towers, GHN
  • Berns, MW
  • Abeysekera, B
  • et al.
Abstract

Alpha-terthienyl (α-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 α-T and characterize its cutaneous phototoxicity in combination with long-wave UV radiation (UVA) in comparison with locally (intradermal) administered α-T. Percutaneous penetration (PC) of 0.1% and 1% α-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/cm2UVA at intervals of 10 min-24 h. Maximum sensitization was achieved 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 μg α-T were injected intradermally and irradiated with UVA: These results indicated that low-dose topical α-T in a nonirritating vehicle can rapidly produce cutaneous photosensitization. Topical α-T/UVA may provide a selective and safer alternative approach for the photochemotherapy of psoriasis and other cutaneous diseases. © 1986.

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