Pharmacokinetics of Alprostadil (Prostaglandin E1) in Patients Undergoing Haemodialysis
- 53 Downloads
Aim: The objective of this study was to evaluate the pharmacokinetics of prostaglandin E1 (PGE1) and its metabolites after infusion of alprostadil in patients undergoing haemodialysis.
Methods: In a single-blind, randomised, 2-way crossover study including eight patients with end-stage renal disease undergoing haemodialysis, alprostadil (60µg PGE1) and placebo were administered by an intravenous infusion over 2 hours in parallel to dialysis. A specific highly sensitive analytical method was used to detect plasma levels of PGE1 and its metabolites.
Results: Endogenous plasma levels of PGE1 were approximately 1 ng/L and did not change during dialysis. Plasma concentrations of unchanged drug increased to 11 ng/L, followed by a rapid drop to baseline levels after the end of the infusion. Comparing PGE1 plasma concentrations measured in the arterial inlet and venous outlet line of the dialyser, no significant extraction of PGE1 was found, which was also reflected by measurements from dialysis fluid. Plasma concentrations of metabolites 13,14-dihydro-prostaglandin E1 (PGE0) and 15-keto-13,14-dihydro-prostaglandin E1 (15-keto-PGE0) confirm the results described for the unchanged drug, indicating that no significant extraction occurs during dialysis. The pharmacokinetic profiles of PGE1 and its metabolites in patients undergoing dialysis are similar to those previously reported for healthy volunteers, with endogenous plasma levels of about 1 ng/L (PGE1 and PGEo) and 10 ng/L (15-keto-PGE0) and maximal plasma concentrations after a 2-hour infusion of about 11, 13 and 330 ng/L (PGE1, PGE0 and 15-keto-PGE0, respectively).
Conclusions: There is no extraction of unchanged PGE1 and its metabolites during an intravenous infusion of alprostadil in parallel with haemodialysis. A dose adjustment for patients undergoing dialysis is not necessary. The pharmacokinetics of PGE1 and its metabolites are similar in patients undergoing dialysis compared with those in healthy volunteers.
KeywordsPlasma Concentration Adis International Limited PGE1 Intravenous Infusion Alprostadil
Unable to display preview. Download preview PDF.
- 3.Olsson AG, Carbon LA. Clinical, haemodynamic and metabolic effects of intraarterial infusion of prostaglandin E1 in patients with peripherical arterial disease. Adv Prostaglandin Throm-boxane Res 1976; 1: 429–32Google Scholar
- 9.Hamberg M, Samuelsson B. On the metabolism of prostaglandin E1 and E2 in man. J Biol Chem 1971; 241: 6713–21Google Scholar
- 11.Schweer H, Meese CO, Watzer B, et al. Determination of prostaglandin E1 and its main plasma metabolites 15-keto-prostaglandin E0 and prostaglandin Eo by gas chromato-graphy/negative ion chemical ionization triple stage quadrupole mass spectrometry. Biol Mass Spectrom 1994; 23: 165–70PubMedCrossRefGoogle Scholar
- 12.Cawello W, editor. Parameters for compartment-free pharma- cokinetics. Aachen: Shaker Verlag, 1999Google Scholar