PHARMACOKINETICS OF NOCLOPROST IN HUMAN VOLUNTEERS AND ITS RELATION TO DOSE

The pharmacokinetics and absolute bioavailability of nocloprost, a syn thetic PGE2-analogue with cytoprotective properties, was investigated in human volunteers as a function of the dose. Ten young male voluntee rs received nocloprost 5 mug i. v. and 100, 200 and 400 mug p. o. in r andom order at weekly intervals. Serum nocloprost levels were monitore d for up to 12 h after each dose, using a specific, validated assay. A fter nocloprost 5 mug i.v. the highest serum level of 373 pg . ml-1 wa s found in the first sample 5 min after injection, and the subsequent decline showed one or two phases, with half-lives of 4 and 49 min. The AUC was 89 pg . h . ml-1, the total plasma clearance was 13.2 ml . mi n-1 . kg-1, and the volume of distribution at steady state was 0.16 1 . kg-1. After oral administration the maximum serum level and AUC incr eased in proportion to the dose. t(max) showed a wide scatter, with an average value of about 30 min independent of the dose. Although not d etectable in every subject, post maximum serum levels declined biphasi cally, with half-lives of ca 10 and 35-40 min. The absolute bioavailab ility after oral administration averaged about 2 % and was independent of the dose.