Pharmacokinetics of perindopril and its metabolites in healthy volunteers

Fundam Clin Pharmacol. 1990;4(2):175-89. doi: 10.1111/j.1472-8206.1990.tb00486.x.

Abstract

Perindopril, an angiotensin converting enzyme (ACE) inhibitor, is converted in vivo to its active diacid metabolite, perindoprilat and to a perindoprilat glucuronide. The pharmacokinetic parameters of perindopril, perindoprilat and perindoprilat glucuronide were evaluated after single administration to healthy volunteers (N = 12) of 8 mg of perindopril tert-butylamine salt by oral route (treatment A), by intravenous route (bolus in 5 min, treatment B) and of an equimolar dose of perindoprilat (6.1 mg) by intravenous route (infusion over 2 h, treatment C). The treatments were administered as a randomised 3-way cross-over design. Plasma samples were collected up to 96 h and urines up to 120 h. Perindopril is rapidly absorbed with an oral bioavailability of 95% and is mainly eliminated by metabolic processes. The formation of perindoprilat is slow and about 20% of the available parent drug is transformed into this metabolite. Elimination profile of perindoprilat is biphasic, with a rapid renal excretion of the free fraction and a long terminal half-life of the fraction bound to ACE. Perindoprilat glucuronide is mainly obtained from perindopril by a pre-systemic first pass metabolism.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial

MeSH terms

  • Administration, Oral
  • Adult
  • Biological Availability
  • Female
  • Glucuronates / urine
  • Half-Life
  • Humans
  • Indoles / administration & dosage
  • Indoles / pharmacokinetics*
  • Indoles / urine
  • Injections, Intravenous
  • Male
  • Perindopril
  • Reference Values

Substances

  • Glucuronates
  • Indoles
  • perindoprilat
  • Perindopril