The pharmacokinetics and pharmacodynamics of perindopril in patients with hepatic cirrhosis.

HH Tsai, KR Lees, Colin Howden, JL Reid

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

1. Perindopril, a new ACE inhibitor, is a prodrug requiring conversion into its active form perindoprilat by hydrolysis in the liver. 2. The pharmacodynamics and pharmacokinetics of perindopril (8 mg oral) and perindoprilat (2 mg intravenously) were studied in a double‐blind randomised crossover study in a group of patients with compensated biopsy‐proven hepatic cirrhosis. 3. Blood pressure and heart rate responses were similar after the two routes of administration as were plasma renin activity and aldosterone levels following dosing. 4. The AUC of perindoprilat after oral administration of perindopril represented 46 +/‐ 4% of the total AUC of perindopril and its metabolite when expressed in molar terms. Comparison with the AUC of perindoprilat after its intravenous administration suggested that 30 +/‐ 6% of the oral dose of perindopril was converted to its active metabolite. 5. The findings are comparable with those in healthy subjects. It appears that the presence of relatively mild hepatic cirrhosis does not significantly alter the pharmacokinetics of perindopril. 1989 The British Pharmacological Society

Original languageEnglish (US)
Pages (from-to)53-59
Number of pages7
JournalBritish Journal of Clinical Pharmacology
Volume28
Issue number1
DOIs
StatePublished - Jan 1 1989
Externally publishedYes

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perindoprilat
Perindopril
Liver Cirrhosis
Pharmacokinetics
Area Under Curve
Prodrugs
Aldosterone
Angiotensin-Converting Enzyme Inhibitors
Renin
Intravenous Administration
Cross-Over Studies
Oral Administration
Healthy Volunteers
Hydrolysis
Heart Rate
Blood Pressure
Liver

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Pharmacology (medical)

Cite this

The pharmacokinetics and pharmacodynamics of perindopril in patients with hepatic cirrhosis. / Tsai, HH; Lees, KR; Howden, Colin; Reid, JL.

In: British Journal of Clinical Pharmacology, Vol. 28, No. 1, 01.01.1989, p. 53-59.

Research output: Contribution to journalArticle

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N2 - 1. Perindopril, a new ACE inhibitor, is a prodrug requiring conversion into its active form perindoprilat by hydrolysis in the liver. 2. The pharmacodynamics and pharmacokinetics of perindopril (8 mg oral) and perindoprilat (2 mg intravenously) were studied in a double‐blind randomised crossover study in a group of patients with compensated biopsy‐proven hepatic cirrhosis. 3. Blood pressure and heart rate responses were similar after the two routes of administration as were plasma renin activity and aldosterone levels following dosing. 4. The AUC of perindoprilat after oral administration of perindopril represented 46 +/‐ 4% of the total AUC of perindopril and its metabolite when expressed in molar terms. Comparison with the AUC of perindoprilat after its intravenous administration suggested that 30 +/‐ 6% of the oral dose of perindopril was converted to its active metabolite. 5. The findings are comparable with those in healthy subjects. It appears that the presence of relatively mild hepatic cirrhosis does not significantly alter the pharmacokinetics of perindopril. 1989 The British Pharmacological Society

AB - 1. Perindopril, a new ACE inhibitor, is a prodrug requiring conversion into its active form perindoprilat by hydrolysis in the liver. 2. The pharmacodynamics and pharmacokinetics of perindopril (8 mg oral) and perindoprilat (2 mg intravenously) were studied in a double‐blind randomised crossover study in a group of patients with compensated biopsy‐proven hepatic cirrhosis. 3. Blood pressure and heart rate responses were similar after the two routes of administration as were plasma renin activity and aldosterone levels following dosing. 4. The AUC of perindoprilat after oral administration of perindopril represented 46 +/‐ 4% of the total AUC of perindopril and its metabolite when expressed in molar terms. Comparison with the AUC of perindoprilat after its intravenous administration suggested that 30 +/‐ 6% of the oral dose of perindopril was converted to its active metabolite. 5. The findings are comparable with those in healthy subjects. It appears that the presence of relatively mild hepatic cirrhosis does not significantly alter the pharmacokinetics of perindopril. 1989 The British Pharmacological Society

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