Pharmacokinetics and distribution of the new antihypertensive agent pinacidil in rat, dog and man.

1. The antihypertensive agent pinacidil was rapidly, and almost completely, absorbed following oral administration of 0.5 mg/kg of the [14C]pinacidil monohydrate to rats and dogs. The half-life was about 1 and 2 h in the two species, respectively. A bioavailability of 80% of unchanged pinacidil in the rat suggests a first-pass effect in this species. 2. After oral and intravenous administration of [14C]pinacidil about 85% of the radioactivity was recovered in the urine and 15% in the faeces in rats and dogs; 80-90% was excreted during the first 24 h. Autoradiographic studies in the rat showed similar distributions after oral and intravenous administration. 3. An oral dose of 5 or 10 mg pinacidil monohydrate was rapidly absorbed in healthy volunteers and had a pharmacokinetic profile very similar to that found in rats and dogs. Concomitant food ingestion did not change the bioavailability of the drug.