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 induce photosensitivity. Antigenic characterization of these photosensitivities, however, is still insufficient. The purpose of the present study was to elucidate further mechanism of photosenstivity induced by APX and PXM using an in vivo model of contact hypersensitivity in guinea pigs. Animals sensitized with ultraviolet-A (UVA)-irradiated 1% APX showed positive reaction in the patch testing to UVA-irradiated 1% APX and 1% thiosalicylate (TOS), while they were negative in challenge with UVA-irradiated 1% PXM, non-irradiated APX and PXM, whereas none of UVA-irradiated or non-irradiated APX and PXM showed positive patch test reaction in animals sensitized with UVA-irradiated 1% PXM or control vehicles. Animals sensitized with 1% TOS were successfully 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 with 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 by photoproducts of APX itself, but not by the biotransformation of APX to PXM.
Sasaki
T
T
Department of Clinical Pharmacy, School of Pharmaceutical Sciences, Tokyo, Japan.
Shimizu
H
H
Tokuyama
S
S
Hariya
T
T
Soh
I
I
Sueki
H
H
Iijima
M
M
Yamamoto
T
T
Kuroiwa
Y
Y
D000818:Animals; D000941:Antigens / Q000276:immunology*; D001565:Benzoates / Q000276:immunology; D003877:Dermatitis, Contact / Q000276:immunology*; D005260:Female; D006168:Guinea Pigs; D010328:Patch Tests; D010787:Photosensitivity Disorders / Q000139:chemically induced* / Q000276:immunology*; D010894:Piroxicam / Q000276:immunology; D011355:Prodrugs; D013438:Sulfhydryl Compounds; D013843:Thiazines / Q000276:immunology; D013849:Thimerosal; D014466:Ultraviolet Rays
D000941:Antigens; D001565:Benzoates; D011355:Prodrugs; D013438:Sulfhydryl Compounds; D013843:Thiazines; C065946:ampiroxicam; D010894:Piroxicam; C026196:2-thiosalicylic acid; D013849:Thimerosal