Antigenic characterization in ampiroxicam-induced photosensitivity using an in vivo model of contact hypersensitivity

Ampiroxicam (APX), a prodrug of piroxicam (PXM), has been reported to induc e photosensitivity. Antigenic characterization of these photosensitivities, however, is still insufficient. The purpose of the present study was to el ucidate further mechanism of photosensitivity induced by APX and PXM using an in vivo model of contact hypersensitivity in guinea pigs. Animals sensit ized with ultraviolet-A (UVA)-irradiated 1% APX showed positive reaction in the patch testing to UVA-irradiated 1% APX and 1% thiosalicylate (TOS), wh ile they were negative in challenge with UVA-irradiated 1% PXM, non-irradia ted APX and PXM, whereas none of UVA-irradiated or non-irradiated APX and P XM showed positive patch test reaction in animals sensitized with UVA-irrad iated 1% PXM or control vehicles. Animals sensitized with 1%, TOS were succ essfully challenged by 1% TOS and cross-reacted with UVA-irradiated 1% APX; however, they failed to react with UVA-irradiated PXM, non-irradiated APX and PXM. Indeed, the in vitro study revealed that the concentration of APX was easily reduced by the increase of UVA irradiation dose, as compared wit h that of PXM. Interestingly, absorption spectrum of UVA-irradiated APX was similar to that of TOS, which is thought to be an active hapten of PXM. In the present study, we succeeded in the development of a novel animal model reflecting the clinical observations. Furthermore, these results suggested that contact hypersensitivity induced by UVA-irradiated APX is developed b y photoproducts of APX itself, but not by the biotransformation of APX to P XM. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved.