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Pharmacokinetics of perindopril and its metabolites in healthy volunteers
Author(s) -
Devissaguet JP,
Ammoury N.,
Devissaguet M.,
Perret L.
Publication year - 1990
Publication title -
fundamental and clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.655
H-Index - 73
eISSN - 1472-8206
pISSN - 0767-3981
DOI - 10.1111/j.1472-8206.1990.tb00486.x
Subject(s) - perindopril , active metabolite , pharmacokinetics , pharmacology , metabolite , medicine , oral administration , bioavailability , chemistry , endocrinology , blood pressure
Summary— 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.