Pharmacokinetics of intravenous ataprost alfadex, a new prostaglandin I2 analog in healthy volunteers.

Abstract

Ataprost alfadex [5(E),-6,9-deoxa-6,9 alpha-methylene-15-cyclopentyl-16,17,18,19,20-pentanor- PGI2 alpha-cyclodextrin clathrate] is a novel PGI2 derivative. From animal studies, it is expected to be a more potent inhibitor of platelet aggregation and less hypotensive than PGI2. The pharmacokinetics of ataprost were studied in 9 healthy male volunteers during and after i.v. infusion for 2 hours at the rates of 2.5 (n = 5) and 10 ng/kg/min (n = 4). Both treatments were well tolerated by the subjects. At the end of the infusion, plasma levels of 191 +/- 76 (mean +/- SD) and 645 +/- 191 pg/ml were reached, declining rapidly with half-lives of 6.7 +/- 3.0 and 5.5 +/- 0.84 minutes at the lower and higher infusion rates, respectively. The area under the plasma concentration-time curve extrapolated to infinity increased with the dose as follows: 28.7 +/- 9.8 and 80.9 +/- 24.8 ng.min/ml. The unchanged drug was not detected in urine but a metabolite was recovered in it, reaching up to 6.0 +/- 0.85% of the total dose within the first 24 hours, the most part of which was recovered within the first 4 hours.