Pharmacokinetics and biotransformation of the prostacyclin analogue, ZK 36 374, in the monkey (Macaca fascicularis).

The pharmacokinetics of ZK 36 374 after intravenous, oral and topical administrations to female monkeys has been investigated using tritium-labelled drug. Following intravenous injection of 2 and 200 microgram/kg a triphasic decline in the plasma levels of labelled compounds was observed with half-lives of 45 min, 4.3 h and 1.7 d. The half-life of the unchanged drug was 13 min. Almost 10% of an oral dose of 200 microgram/kg were bioavailable exhibiting maximum plasma levels of 5.7 +/- 3.6 ng/ml. The drug was totally metabolized and excreted mainly with the urine in the form of more than 10 metabolites. Following topical application of 1 mg, 5.5 +/- 2.2% of the dose was percutaneously absorbed using a TRIS-buffered solution of ZK 36 374 and 1.3 +/- 0.2% was absorbed applying an ethanolic solution of the drug. The plasma levels of labelled compounds were practically constant during the whole observation period of 36 hours.