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|Title:||Single-dose and steady-state pharmacokinetics and pharmacodynamics of perindopril in hypertensive subjects.|
|Authors:||Louis, William J;Workman, B S;Conway, Elizabeth L;Worland, P;Rowley, K;Drummer, Olaf H;McNeil, John J;Harris, G;Jarrott, B|
|Affiliation:||Department of Clinical Pharmacology and Therapeutics, Austin Hospital, Heidelberg, Victoria, Australia.|
|Citation:||Journal of Cardiovascular Pharmacology; 20(3): 505-11|
|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 less than or equal to 2 h after dosing with an elimination t1/2 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 t1/2 of 40 h. Levels of the perindopril glucuronide peaked approximately 0.5 h later than perindopril, with an elimination t1/2 of approximately 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 predose 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.|
|Internal ID Number:||1279299|
Angiotensin-Converting Enzyme Inhibitors.pharmacokinetics.pharmacology
Blood Pressure.drug effects
Chromatography, Ion Exchange
Dose-Response Relationship, Drug
|Appears in Collections:||Journal articles|
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