Pharmacokinetics of ramipril in the elderly.

Ramipril (HOE 498) is a pro-drug of which the main metabolite (HOE 498 diacid or ramiprilat) is a potent angiotensin converting enzyme inhibitor. Thirteen healthy white volunteers (5 females and 8 males, ages 65 to 76 years) participated in a study to investigate the pharmacokinetics of HOE 498 in the elderly. After administration of 10 mg of HOE 498, sequential urine and serum specimens were obtained for assay of HOE 498 and metabolites (HOE 498-glucuronide, diacid, diacid-glucuronide, diketopiperazine and diketopiperazine acid). Side effects, clinical chemistry and hematology were monitored. HOE 498 reached peak concentrations of 62.4 +/- 23.3 ng/ml in serum after 0.7 +/- 0.3 hours. Serum levels decreased with an apparent half-life of 0.9 +/- 0.4 hours. The diacid was rapidly formed in serum, reaching peak concentrations of 40.6 +/- 14.0 ng/ml after 2.0 +/- 0.6 hours and declining with a half-life of 2.2 +/- 0.5 hours. A prolonged terminal phase of serum concentration versus time curve was observed at concentrations less than 1 ng/ml. The mean recovery of HOE 498 and metabolites in urine, up to 26 hours after administration, was 35 +/- 14% of the dose. The apparent half-lives, calculated from urine parameters, for HOE 498 and the diacid were 2.6 +/- 0.9 and 4.0 +/- 1.1 hours, respectively. The mean peak concentration and half-life of HOE 498 in serum are slightly higher in the elderly than in younger volunteers. Complete urinary collection was not possible, but urinary recovery did not seem different from younger volunteers.