Pharmacokinetics of nocloprost in human volunteers and its relation to dose.
The pharmacokinetics and absolute bioavailability of nocloprost, a synthetic PGE2-analogue with cytoprotective properties, was investigated in human volunteers as a function of the dose. Ten young male volunteers received nocloprost 5 micrograms i.v. and 100, 200 and 400 micrograms p.o. in random order at weekly intervals. Serum nocloprost levels were monitored for up to 12 h after each dose, using a specific, validated assay. After nocloprost 5 micrograms i.v. the highest serum level of 373 pg.ml-1 was 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.min-1.kg-1, and the volume of distribution at steady state was 0.16 l.kg-1. After oral administration the maximum serum level and AUC increased in proportion to the dose. tmax showed a wide scatter, with an average value of about 30 min independent of the dose. Although not detectable in every subject, post maximum serum levels declined biphasically, with half-lives of ca 10 and 35-40 min. The absolute bioavailability after oral administration averaged about 2% and was independent of the dose.
Tüber
U
U
Institut für Pharmakokinetik, Schering AG, Berlin, Germany.
Brudny-Klöppel
M
M
Jakobs
U
U
Madetzki
C
C
Mahler
M
M
D000284:Administration, Oral; D000328:Adult; D001682:Biological Availability; D004305:Dose-Response Relationship, Drug; D006207:Half-Life; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D008657:Metabolic Clearance Rate; D011461:Prostaglandins F, Synthetic / Q000008:administration & dosage / Q000493:pharmacokinetics*
D011461:Prostaglandins F, Synthetic; C048895:nocloprost