Influence of age on the pharmacokinetics and pharmacodynamics of perindopril

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Abstract
Perindopril is the ester prodrug of the angiotensin converting enzyme inhibitor S-09780. 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 < 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 < 0.03). Dose reduction of approximately 50% is suggested for elderly patients with further adjustment proportional to any preexisting diminished renal function.