Sodium 5-(3′-pyridinylmethyl)benzofuran-2-carboxylate (U-63557A), a new, selective thromboxane synthase inhibitor: Intravenous and oral pharmacokintics in dogs and correlations with ex situ thromboxane B 2 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 μg/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 B 2 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.