Pharmacokinetics of iloprost in patients with chronic renal failure and on maintenance haemodialysis.
Iloprost is a potent, chemically stable prostacyclin-mimetic for which therapeutic efficacy has been proven in patients with peripheral arterial occlusive disease (PAOD) and in those suffering from Raynaud's phenomenon. In volunteers and PAOD-patients the pharmacokinetics of iloprost after intravenous (i.v.) infusion treatment was characterized by dose-dependent steady-state plasma levels, a terminal half-life of approximately 20-30 min, and a total clearance of 15-20 ml/min/kg. Bioinactivation was mainly due to beta-oxidation. In the present study the pharmacokinetics of iloprost was investigated in 21 patients suffering from renal insufficiency, which either required haemodialysis or not. They were treated by one hour i.v. infusion with 1 ng/kg/min and blood samples were taken during and after the end of infusion. Due to technical sampling problems iloprost pharmacokinetics could only be calculated for seven dialysis and eight non-dialysis patients. In the dialysis patients steady-state levels were 114 to 320 pg/ml as compared to 36 to 70 pg/ml in the non-dialysis group. Half-lives were similar in both groups: alpha-phase: 0.05 h and beta-phase: 0.5 h. The total clearance was 2.6 to 8.0 ml/min/kg (dialysis patients) and 13.2 to 25.8 ml/min/kg (non-dialysis patients). The present study demonstrated that the pharmacokinetic profile of iloprost in patients with renal failure (not subject to haemodialysis) was similar to that observed in PAOD-patients and volunteers. In patients on maintenance haemodialysis, iloprost clearance was reduced by a factor of four. The iloprost dose regimen required in general (due to interindividual variability in response) a careful dose titration.
Hildebrand
M
M
Department of Pharmacokinetics, Schering AG, Berlin, Federal Republic of Germany.
Krause
W
W
Fabian
H
H
Koziol
T
T
Neumayer
H H
HH
D000328:Adult; D000368:Aged; D001794:Blood Pressure / Q000187:drug effects; D003404:Creatinine / Q000097:blood; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D016285:Iloprost / Q000008:administration & dosage / Q000493:pharmacokinetics*; D007262:Infusions, Intravenous; D007676:Kidney Failure, Chronic / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D006435:Renal Dialysis
D003404:Creatinine; D016285:Iloprost