Sodium 5-(3'-pyridinylmethyl)benzofuran-2-carboxylate (U-63557A), a new, selective thromboxane synthase inhibitor: intravenous and oral pharmacokinetics in dogs and correlations with ex situ thromboxane B2 production.
The pharmacokinetics of a new, selective thromboxane synthase inhibitor, sodium 5-(3'-pyridinylmethyl)benzofuran-2-carboxylate were determined for single dose, bolus intravenous injections (1, 3, and 10 mg/kg); for continuous 24 hr infusions (10 and 30 micrograms/kg/min); and for oral doses of gelatin encapsulated powdered drug (3, 10, and 30 mg/kg). Drug disappeared biexponentially after intravenous administration, and plasma concentrations were proportional to the dose. Absorption of drug occurred rapidly after its oral administration; peak plasma levels occurred 1-2 hours after ingestion, and circulating drug was detectable within 30 minutes. For all experiments, inhibition of cellular thromboxane B2 production, ex situ, corresponded with plasma drug levels and its reactivation corresponded with disappearance of the drug indicating that it was not accumulated by platelets.
D000284:Administration, Oral; D000818:Animals; D001572:Benzofurans / Q000494:pharmacology*; D002851:Chromatography, High Pressure Liquid; D004285:Dogs; D006207:Half-Life; D007275:Injections, Intravenous; D007700:Kinetics; D010088:Oxidoreductases / Q000037:antagonists & inhibitors*; D013929:Thromboxane B2 / Q000096:biosynthesis*; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors*; D013931:Thromboxanes / Q000096:biosynthesis*
D001572:Benzofurans; D013931:Thromboxanes; D013929:Thromboxane B2; D010088:Oxidoreductases; D013930:Thromboxane-A Synthase; C039936:furegrelate