Antiplatelet effects of fenflumizole, a new anti-inflammatory drug, in dogs.
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.
D000244:Adenosine Diphosphate / Q000494:pharmacology; D000284:Administration, Oral; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000097:blood / Q000494:pharmacology*; D003094:Collagen / Q000494:pharmacology; D004285:Dogs; D007093:Imidazoles / Q000097:blood / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D010974:Platelet Aggregation / Q000187:drug effects*; D013997:Time Factors
D000893:Anti-Inflammatory Agents; D007093:Imidazoles; D000244:Adenosine Diphosphate; D003094:Collagen; C038996:fenflumizole