Influence of age on the pharmacokinetics and pharmacodynamics of perindopril

• Published in: Clinical pharmacology and therapeutics Vol. 44; no. 4; p. 418
• Main Authors: Lees, K R, Green, S T, Reid, J L
• Format: Journal Article
• Language: English
• Published: United States 01.10.1988
• Subjects: Adult; Age Factors; Aged; Angiotensin-Converting Enzyme Inhibitors - adverse effects; Angiotensin-Converting Enzyme Inhibitors - pharmacokinetics; Antihypertensive Agents - adverse effects; Antihypertensive Agents - pharmacokinetics; Female; Humans; Indoles - adverse effects; Indoles - pharmacokinetics; Indoles - pharmacology; Male; Peptidyl-Dipeptidase A - blood; Perindopril
• ISSN: 0009-9236
• DOI: 10.1038/clpt.1988.174

Perindopril is the ester prodrug of the angiotensin converting enzyme inhibitor S-9780. The influence of age on the pharmacokinetics and pharmacodynamics of S-9780 (1 mg administered intravenously) and perindopril (8 mg administered orally) was examined in a double-blind, crossover, acute study in eight young (29 +/- 3 years) and eight elderly (71 +/- 3 years) healthy subjects. Mild headache and light-headedness were the only adverse effects and were more common in the younger subjects. Blood pressure fall was greater in the elderly even after correction for starting blood pressure. Bioavailability of S-9780 was increased in the elderly (35% +/- 17% compared with 19% +/- 7%; p less than 0.025) mainly because of increased conversion rather than absorption. Renal clearance of S-9780 was lower in the elderly (67 +/- 31 ml/min compared with 110 +/- 39 ml/min; p less than 0.03). Dose reduction of approximately 50% is suggested for elderly patients with further adjustment proportional to any preexisting diminished renal function.