Antiplatelet Effects of Fenflumizole, a New Anti-Inflammatory Drug, in Dogs

抄録

Fenflumizole (2-(2, 4-difluorophenyl)-4, 5-bis(4-methoxyphenyl) imidazole) was given to dogs in a single oral dose of 3 or 10 mg/kg. The plasma concentrations of fenflumizole and the two metabolites (mono and di-demethyl forms) attained to the peak level 1-2 hr after dosing of fenflumizole, returning to near the predose levels 8 hr after the dosing. Fenflumizole (10 mg/kg) given orally significantly inhibited collagen- and ADP-induced platelet aggregations ex vivo over 4 hr after the dosing. Fenflumizole effectively inhibited in vitro collagen-induced platelet aggregation, but failed to prevent ADP-induced aggregation. The mono-demethyl form of fenflumizole inhibited in vitro ADP- and collagen-induced aggregations, but the di-demethyl form was ineffective in inhibiting them.