Pharmacokinetics of perindopril and its metabolites in healthy volunteers.
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.
Devissaguet
J P
JP
UA CNRS 1218, Laboratoire de Pharmacie Galénique et Biopharmacie, Université Paris Sud, Chatenay-Malabry, France.
Ammoury
N
N
Devissaguet
M
M
Perret
L
L
D000284:Administration, Oral; D000328:Adult; D001682:Biological Availability; D005260:Female; D005965:Glucuronates / Q000652:urine; D006207:Half-Life; D006801:Humans; D007211:Indoles / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000652:urine; D007275:Injections, Intravenous; D008297:Male; D020913:Perindopril; D012016:Reference Values
D005965:Glucuronates; D007211:Indoles; C053500:perindoprilat; D020913:Perindopril