Skip to main content
NCBI home page
British Journal of Clinical Pharmacology logoLink to British Journal of Clinical Pharmacology
. 1992 Mar;33(3):326–328. doi: 10.1111/j.1365-2125.1992.tb04045.x

The pharmacokinetics of perindopril in patients with liver cirrhosis.

M Thiollet 1, C Funck-Brentano 1, J D Grangé 1, M Midavaine 1, G Resplandy 1, P Jaillon 1
PMCID: PMC1381285  PMID: 1576057

Abstract

Perindopril is a non-sulphydryl angiotensin converting enzyme (ACE) inhibitor which requires hydrolysis to its active metabolite, perindoprilat, to produce its effects. Ten cirrhotic patients with mild to severe disease were studied after oral administration of a single 8 mg dose of perindopril as its tert-butylamine salt. Compared with a historical control group of young healthy volunteers receiving the same single oral dose of perindopril, mean AUC values of the prodrug perindopril were double in patients with liver cirrhosis (602 +/- 294 s.d. ng ml-1 h vs 266 +/- 70 s.d. ng ml-1 h) whereas the mean AUC of perindoprilat was found to be similar (134 +/- 139 ng ml-1 h vs 120 +/- 29 ng ml-1 h). The partial metabolic clearance of perindopril to perindoprilat was much lower in the cirrhotics (26 +/- 12 ml min-1 vs 58 +/- 22 ml min-1). The maximum inhibition of plasma ACE activity measured in the cirrhotic patients (87.5 +/- 5.1%) was comparable with that previously reported with perindopril in patients with mild hepatic impairment as well as in patients with essential hypertension. We suggest that liver cirrhosis may be associated with imparied deesterification of perindopril to its active metabolite perindoprilat but that no dosage adjustment of perindopril is required in cirrhotic patients.

Full text

PDF
326

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Baba T., Murabayashi S., Tomiyama T., Takebe K. The pharmacokinetics of enalapril in patients with compensated liver cirrhosis. Br J Clin Pharmacol. 1990 Jun;29(6):766–769. doi: 10.1111/j.1365-2125.1990.tb03700.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bussien J. P., d'Amore T. F., Perret L., Porchet M., Nussberger J., Waeber B., Brunner H. R. Single and repeated dosing of the converting enzyme inhibitor perindopril to normal subjects. Clin Pharmacol Ther. 1986 May;39(5):554–558. doi: 10.1038/clpt.1986.95. [DOI] [PubMed] [Google Scholar]
  3. Chiou W. L. Critical evaluation of the potential error in pharmacokinetic studies of using the linear trapezoidal rule method for the calculation of the area under the plasma level--time curve. J Pharmacokinet Biopharm. 1978 Dec;6(6):539–546. doi: 10.1007/BF01062108. [DOI] [PubMed] [Google Scholar]
  4. Devissaguet J. P., Ammoury N., Devissaguet M., Perret L. Pharmacokinetics of perindopril and its metabolites in healthy volunteers. Fundam Clin Pharmacol. 1990;4(2):175–189. doi: 10.1111/j.1472-8206.1990.tb00486.x. [DOI] [PubMed] [Google Scholar]
  5. Doucet L., De Veyrac B., Delaage M., Cailla H., Bernheim C., Devissaguet M. Radioimmunoassay of a new angiotensin-converting enzyme inhibitor (perindopril) in human plasma and urine: advantages of coupling anion-exchange column chromatography with radioimmunoassay. J Pharm Sci. 1990 Aug;79(8):741–745. doi: 10.1002/jps.2600790817. [DOI] [PubMed] [Google Scholar]
  6. Grislain L., Mocquard M. T., Dabe J. F., Bertrand M., Luijten W., Marchand B., Resplandy G., Devissaguet M. Interspecies comparison of the metabolic pathways of perindopril, a new angiotensin-converting enzyme (ACE) inhibitor. Xenobiotica. 1990 Aug;20(8):787–800. doi: 10.3109/00498259009046893. [DOI] [PubMed] [Google Scholar]
  7. Lecocq B., Funck-Brentano C., Lecocq V., Ferry A., Gardin M. E., Devissaguet M., Jaillon P. Influence of food on the pharmacokinetics of perindopril and the time course of angiotensin-converting enzyme inhibition in serum. Clin Pharmacol Ther. 1990 Mar;47(3):397–402. doi: 10.1038/clpt.1990.45. [DOI] [PubMed] [Google Scholar]
  8. Lees K. R., Green S. T., Reid J. L. Influence of age on the pharmacokinetics and pharmacodynamics of perindopril. Clin Pharmacol Ther. 1988 Oct;44(4):418–425. doi: 10.1038/clpt.1988.174. [DOI] [PubMed] [Google Scholar]
  9. Lees K. R., Reid J. L. Effects of intravenous S-9780, an angiotensin-converting enzyme inhibitor, in normotensive subjects. J Cardiovasc Pharmacol. 1987 Aug;10(2):129–135. doi: 10.1097/00005344-198708000-00001. [DOI] [PubMed] [Google Scholar]
  10. Lees K. R., Reid J. L. Haemodynamic and humoral effects of oral perindopril, an angiotensin converting enzyme inhibitor, in man. Br J Clin Pharmacol. 1987 Feb;23(2):159–164. doi: 10.1111/j.1365-2125.1987.tb03024.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Lees K. R., Reid J. L. The haemodynamic and humoral effects of treatment for one month with the angiotensin converting enzyme inhibitor perindopril in salt replete hypertensive patients. Eur J Clin Pharmacol. 1987;31(5):519–524. doi: 10.1007/BF00606623. [DOI] [PubMed] [Google Scholar]
  12. Ohnishi A., Tsuboi Y., Ishizaki T., Kubota K., Ohno T., Yoshida H., Kanezaki A., Tanaka T. Kinetics and dynamics of enalapril in patients with liver cirrhosis. Clin Pharmacol Ther. 1989 Jun;45(6):657–665. doi: 10.1038/clpt.1989.87. [DOI] [PubMed] [Google Scholar]
  13. Richer C., Thuillez C., Giudicelli J. F. Perindopril, converting enzyme blockade, and peripheral arterial hemodynamics in the healthy volunteer. J Cardiovasc Pharmacol. 1987 Jan;9(1):94–102. [PubMed] [Google Scholar]
  14. Ryan J. W., Chung A., Ammons C., Carlton M. L. A simple radioassay for angiotensin-converting enzyme. Biochem J. 1977 Nov 1;167(2):501–504. doi: 10.1042/bj1670501. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Tsai H. H., Lees K. R., Howden C. W., Reid J. L. The pharmacokinetics and pharmacodynamics of perindopril in patients with hepatic cirrhosis. Br J Clin Pharmacol. 1989 Jul;28(1):53–59. doi: 10.1111/j.1365-2125.1989.tb03505.x. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from British Journal of Clinical Pharmacology are provided here courtesy of British Pharmacological Society

RESOURCES