The effect of haemodialysis on the pharmacokinetics of perindoprilat after long-term perindopril

Eur J Clin Pharmacol. 1993;44(2):183-7. doi: 10.1007/BF00315478.

Abstract

We have studied the pharmacokinetics of perindoprilat, the active metabolite of perindopril, in 7 hypertensive patients undergoing haemodialysis after short-term and long-term (1 month) perindopril. We also measured angiotensin-converting enzyme activity. Each subject took 2 mg of perindopril after a 4-hour haemodialysis. Serial blood samples were obtained each hour during dialysis and between dialysis (7 samples over 44 h). Perindoprilat steady state was reached within 5 haemodialysis sessions. There was a high degree of angiotensin converting enzyme inhibition after the first dose. Administration for 1 month did not modify the time to peak perindoprilat concentration but significantly increased the mean maximal concentration: 10.2 versus 26.8 ng.ml-1. The mean accumulation ratio was 3.5. The mean reduction in perindoprilat concentration after dialysis was greater than 50%. Perindoprilat haemodialysis clearance was 62 ml.min-1 after the first administration and 72 ml.min-1 after 1 month. Tolerance of perindopril was good throughout the study. Treatment can be begun with 2 mg of perindopril after haemodialysis in hypertensive patients undergoing haemodialysis.

MeSH terms

  • Adult
  • Aged
  • Angiotensin-Converting Enzyme Inhibitors / pharmacology
  • Blood Pressure / drug effects
  • Female
  • Heart Rate / drug effects
  • Humans
  • Indoles / adverse effects
  • Indoles / pharmacokinetics*
  • Indoles / pharmacology
  • Male
  • Middle Aged
  • Perindopril
  • Radioimmunoassay
  • Renal Dialysis*
  • Ultrafiltration

Substances

  • Angiotensin-Converting Enzyme Inhibitors
  • Indoles
  • perindoprilat
  • Perindopril