DOSE PROPORTIONAL PHARMACOKINETICS OF ALPROSTADIL (PROSTAGLANDIN E(1)) IN HEALTHY-VOLUNTEERS FOLLOWING INTRAVENOUS-INFUSION

Prostaglandin E(1) (PGE(1)) (30, 60, 120 mu g) 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 PGE(1), PGE(0) and 15-keto-PGE(0), 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 mu g PGE(1), endogenous plasma PGE(1) 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. PGE(0) 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-PGE(0) 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 mu g PGE(1) 2 h(-1) there was a linear increase of C-max 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%.