Metabolism and pharmacokinetics of prostaglandin E1 administered by intravenous infusion in human subjects.
In a single-blind, randomized, two-way cross-over study with 12 healthy male volunteers, 60 micrograms of prostaglandin E1 (PGE1) or placebo was administered by intravenous infusion during a 120-min period. PGE1, 13,14-dihydro-PGE1 (PGE0) and 15-keto-PGE0 plasma concentrations were measured by a highly specific and sensitive GC-MS/MS method. Endogenous PGE1 plasma concentrations ranged between 1.2 and 1.8 pg.ml-1. Endogenous PGE0 and 15-keto-PGE0 plasma concentrations varied from 0.8 to 1.3 pg.ml-1 and from 4.2 to 6.0 pg/ml respectively. During intravenous infusion of PGE1, plasma PGE1 concentrations rose to a level twice as high as during the placebo infusion. In contrast, PGE0 plasma concentrations were 8 times higher during PGE1 infusion than during placebo infusion, and 15-keto-PGE0 plasma concentrations were 20 times higher. The new analytical method has thus been useful to describe the pharmacokinetics of PGE1 and its metabolites PGE0 and 15-keto-PGE0, during and after intravenous infusion of PGE1.
Cawello
W
W
Department of Biomathematics, Schwarz Pharma AG, Monheim, Germany.
Schweer
H
H
Müller
R
R
Bonn
R
R
Seyberth
H W
HW
D000328:Adult; D000527:Alprostadil / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000097:blood / Q000493:pharmacokinetics*; D008401:Gas Chromatography-Mass Spectrometry; D006207:Half-Life; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D016037:Single-Blind Method
C086635:prostaglandin E0; D000527:Alprostadil; C086634:15-keto-prostaglandin E0