Development of a radioimmunoassay and its application to the pharmacokinetics of the stable prostacyclin analogue, nileprost, in the rat.
The development of a sensitive radioimmunoassay for measuring concentrations of nileprost , a stable prostacyclin analogue, is described. The RIA method, furthermore, is applied to evaluate the pharmacokinetics of nileprost in the rat. Antiserum against nileprost was raised in rabbits by immunizing with the drug coupled to bovine serum albumin via the carboxylic group. Nileprost is extracted from plasma samples using a reversed-phase Sep- PakR cartridge. The limit of detection is less than 10 pg/ml. At the 1.25 ng/ml level intra- and inter-assay variations of 6 and 16% were calculated. Following intravenous injection of 200 micrograms/kg to female Wistar rats, a three-phasic decline in plasma levels was observed with half-lives of 10 min, 30 min and 7.4 h. Oral doses of 200 and 2,000 micrograms/kg were very rapidly absorbed exhibiting maximum concentrations in the plasma of 20 and 30 ng/ml as early as 5 min postadministration . Bioavailability of nileprost was calculated to be 21 and 13% of the dose. The disposition half-life was 5-7 h in both cases.
D000818:Animals; D001682:Biological Availability; D011464:Epoprostenol / Q000097:blood* / Q000031:analogs & derivatives; D005260:Female; D006207:Half-Life; D007700:Kinetics; D011863:Radioimmunoassay / Q000379:methods*; D051381:Rats; D011919:Rats, Inbred Strains
D011464:Epoprostenol; C038832:nileprost