Summary
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.
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Guérin, A., Resplandy, G., Marchais, S. et al. The effect of haemodialysis on the pharmacokinetics of perindoprilat after long-term perindopril. Eur J Clin Pharmacol 44, 183–187 (1993). https://doi.org/10.1007/BF00315478
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DOI: https://doi.org/10.1007/BF00315478