Antithrombotic and ulcerogenic effects of fenflumizole, a new anti-inflammatory imidazole derivative, in rats.

Fenflumizole (2-(2,4-difluorophenyl)-4,5-bis(4-methoxyphenyl) imidazole) was given to rats in a single oral dose of 30 mg/kg. The plasma concentration of fenflumizole reached a peak 2-3 hr after the dosing in non-fasted as well as fasted rats. Two metabolites (demethylation products) of fenflumizole were also detected in the plasma, but only in traces. Fenflumizole (30 and 100 mg/kg) and aspirin (100 mg/kg), given orally 2 hr prior to i.v. arachidonate (80 mg/kg), were effective in protecting the rats from death. Fenflumizole in single oral doses of 100 to 800 mg/kg dose-dependently developed erosions in the rat gastric mucosa, but was much less ulcerogenic than aspirin (3.12-200 mg/kg). Thus, fenflumizole seems to possess a potent antithrombotic activity and a relatively low gastro-ulcerogenicity in rats.