Dose proportional pharmacokinetics of alprostadil (prostaglandin E1) in healthy volunteers following intravenous infusion.

Abstract

Prostaglandin E1 (PGE1) (30, 60, 120 micrograms) was administered by intravenous infusion over a 120 min period in an open, three way randomized, cross-over study to 12 healthy male volunteers. For the evaluation of PGE1, PGE0 and 15-keto-PGE0, blood samples were drawn prior to, during and after the infusion. Analytical measurements were performed by gas chromatography/negative ion chemical ionization triple stage quadruple mass spectrometry, a highly specific and sensitive GC/MS/MS-method. During intravenous infusion of 30, 60 and 120 micrograms PGE1, endogenous plasma PGE1 concentrations increased from 1.7 +/- 0.8 to 4.2 +/- 1.1, 6.7 +/- 1.0 and 11.0 +/- 1.9 pg ml-1 respectively. PGE0 plasma concentrations increased from endogenous levels of 1.3 +/- 1.0 pg ml-1 to 7.6 +/- 2.1, 14.1 +/- 3.7 and 28.0 +/- 3.0 pg ml-1 respectively, whilst 15-keto-PGE0 plasma concentrations increased from endogenous levels of 10.2 +/- 13.9 pg ml-1 to 99.3 +/- 27.9, 190.4 +/- 52.5 and 357.2 +/- 72.6 pg ml-1 respectively. Within the dose range of 30-120 micrograms PGE1 2 h-1 there was a linear increase of Cmax and AUC with the dose. The results of the analysis of variance after baseline and dose-correction show a 90% confidence interval in the bioequivalence acceptance range of 80 to 125%.