Single-dose and steady-state pharmacokinetics and pharmacodynamics of perindopril in hypertensive subjects

W. J. Louis, B. S. Workman, E. L. Conway, P. Worland, K. Rowley, O. Drummer, J. J. McNeil, G. Harris, B. Jarrott

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Abstract

In a double-blind, placebo-controlled, parallel group study, 24 essential hypertensive subjects were randomised to receive either placebo or 2, 4, or 8 mg perindopril. Perindopril, its deesterified metabolite, perindoprilat, and perindoprilat glucuronide were separated with an ion-exchange resin and determined by a radioimmunoassay (RIA). Pharmacokinetic and pharmacodynamic parameters were estimated for 96 h after the first dose and after 4-week once-daily treatment. Perindopril peak levels were achieved in < 2 h after dosing with an elimination t½ of 1–2 h. Peak levels of perindoprilat were achieved more slowly, reaching a maximum level 5–8 h after dosing, and had an elimination t½ of 40 h. Levels of the perindopril glucuronide peaked ∼0.5 h later than perindopril, with an elimination t½ of ∼2 h. Perindopril, perindoprilat, and its glucuronide conjugate followed linear kinetics in the dose range of 2–8 mg, and there was no evidence of accumulation with chronic dosing. Perindopril 4 and 8 mg produced significant decreases in pre-dose blood pressure (BP) with chronic dosing, with maximal decreases occurring 5–7 h after dosing. Perindopril also produced a prolonged dose-dependent inhibition of plasma angiotensin-converting enzyme (ACE) activity that was maximum after 4 h and had not fully recovered by 48 h after a single dose.

Original languageEnglish
Pages (from-to)505-511
Number of pages7
JournalJournal of Cardiovascular Pharmacology
Volume20
Issue number3
DOIs
Publication statusPublished - 1 Jan 1992
Externally publishedYes

Keywords

  • Hypertension
  • Perindopril
  • Pharmacodynamics
  • Pharmacokinetics
  • Steady state

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