title: Pharmacokinetics and biotransformation of the prostacyclin analogue, ZK 36 374, in the monkey (Macaca fascicularis).
abstract: 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.
mesh_terms: D000284:Administration, Oral; D000287:Administration, Topical; D000818:Animals; D001711:Biotransformation; D011464:Epoprostenol / Q000008:administration & dosage / Q000378:metabolism*; D005260:Female; D016285:Iloprost; D007275:Injections, Intravenous; D007700:Kinetics; D008252:Macaca fascicularis; D011453:Prostaglandins / Q000378:metabolism*
chemical_list: D011453:Prostaglandins; D011464:Epoprostenol; D016285:Iloprost