Pharmacokinetics of alprostadil (prostaglandin E-1) in patients undergoinghaemodialysis

Aim: The objective of this study was to evaluate the pharmacokinetics of pr ostaglandin E-1 (PGE(1)) and its metabolites after infusion of alprostadil in patients undergoing haemodialysis. Methods: In a single-blind, randomised, 2-way crossover study including eig ht patients with end-stage renal disease undergoing haemodialysis, alprosta dil (60 mu g PGE(1)) and placebo were administered by an intravenous infusi on over 2 hours in parallel to dialysis. A specific highly sensitive analyt ical method was used to detect plasma levels of PGE(1) and its metabolites. Results: Endogenous plasma levels of PGE(1) were approximately 1 ng/L and d id not change during dialysis. Plasma concentrations of unchanged drug incr eased to 11 ng/L, followed by a rapid drop to baseline levels after the end of the infusion. Comparing PGE(1) plasma concentrations measured in the ar terial inlet and venous outlet line of the dialyser, no significant extract ion of PGE(1) was found, which was also reflected by measurements from dial ysis fluid. Plasma concentrations of metabolites 13,14-dihydro-prostaglandi n E-1 (PGE(0)) and 15-keto-13,14-dihydro-prostaglandin E-1 (15-keto-PGE(0)) confirm the results described for the unchanged drug, indicating that no s ignificant extraction occurs during dialysis. The pharmacokinetic profiles of PGE(1) and its metabolites in patients unde rgoing dialysis are similar to those previously reported for healthy volunt eers, with endogenous plasma levels of about 1 ng/L (PGE(1) and PGE(0)) and 10 ng/L (15-keto-PGE(0)) and maximal plasma concentrations after a 2-hour infusion of about 11, 13 and 330 ng/L (PGE(1), PGEo(0) and 15-keto-PGE(0), respectively). Conclusions: There is no extraction of unchanged PGE(1) and its metabolites during an intravenous infusion of alprostadil in parallel with haemodialys is. A dose adjustment for patients undergoing dialysis is not necessary. Th e pharmacokinetics of PGE(1) and its metabolites are similar in patients un dergoing dialysis compared with those in healthy volunteers.