Single dose pharmacokinetics of perindopril and its metabolites in hypertensive patients with various degrees of renal insufficiency.

Abstract

1 Perindopril is a prodrug which is hydrolysed in vivo to the active metabolite perindoprilat, an angiotensin-converting enzyme inhibitor. Perindoprilat glucuronide is also found in plasma. 2 The pharmacokinetics of perindopril and its metabolites were studied after administration of a single 4 mg dose to hypertensive patients with various degrees of renal failure. 3 The absorption and elimination of perindopril were not influenced by the degree of renal failure. 4 The mean area under the serum concentration-time curve of the active metabolite perindoprilat increased from 93 ng ml-1 h in subjects with normal renal function to 1106 ng ml-1 in patients with severe renal failure, whereas its half-life varied from 5.0 to 27.4 h. 5 In the same subjects, the mean area under the curve of perindoprilat glucuronide increased from 78 to 513 ng ml-1 h, while its half-life varied from 1.8 h to 7.7 h. 6 Perindopril, perindoprilat, and perindoprilat glucuronide were dialysable. 7 The extent and duration of serum angiotensin-converting enzyme inhibition was augmented in renal failure. The mean area under the inhibition time curve (extrapolated to infinity) increased from 2490%.h in subjects with normal renal function to 42241 %.h in patients with severe renal impairment. The half-life of inhibition varied from 12.1 h to 100.4 h. This effect of renal failure on the pharmacodynamics of perindoprilat was more pronounced than its influence on perindoprilat kinetics. 8 In view of the important influence of renal impairment on the elimination and action of the active substance perindoprilat, a dosage reduction of perindopril is proposed in in patients with renal failure.(ABSTRACT TRUNCATED AT 250 WORDS)

• Authors: G A Verpooten, P M Genissel, J R Thomas, M E De Broe
• Journal: British journal of clinical pharmacology (Br J Clin Pharmacol) Vol. 32 Issue 2 Pg. 187-92 (Aug 1991) ISSN: 0306-5251 [Print] England
• PMID: 1657092 (Publication Type: Journal Article)

Chemical References

• Angiotensin-Converting Enzyme Inhibitors
• Glucuronates
• Indoles
• perindoprilat
• Peptidyl-Dipeptidase A
• Perindopril

Topics

• Adult
• Angiotensin-Converting Enzyme Inhibitors (metabolism, pharmacokinetics)
• Blood Pressure (drug effects)
• Female
• Glucuronates (metabolism)
• Half-Life
• Humans
• Hypertension, Renal (metabolism)
• Indoles (blood, metabolism, pharmacokinetics)
• Kidney Failure, Chronic (metabolism)
• Male
• Middle Aged
• Peptidyl-Dipeptidase A (blood)
• Perindopril
• Renal Dialysis