Abstract
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 24h. Autoradiographic studies in the rat showed similar distributions after oral and intravenous administration.
3. An oral dose of 5 or 10mg 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.