Pharmacokinetics and pharmacodynamics of ramipril in renal failure.

The pharmacokinetics and pharmacodynamics of the novel angiotensin converting enzyme (ACE) inhibitor ramipril were studied in 6 patients with a glomerular filtration rate of less than 20 ml/min/1.73 m2 of body surface area. A single oral dose of 5 mg was given and serum concentrations of the compound and its diacid, the active metabolite (ramiprilat), as well as ACE activity, blood pressure and pulse rate were monitored for 28 days. The original compound reached peak serum concentrations of 42.8 +/- 26.5 ng/ml about 1 hour after dosing and was completely eliminated from the serum after 24 hours. Ramiprilat reached peak values of 14.4 +/- 11.6 ng/ml after about 6 hours. In contrast with the parent compound, low concentrations of ramiprilat were still detected in the serum after 28 days. ACE activity decreased to approximately 5% of baseline values, remained low for the next 48 hours, then increased slowly thereafter but reached only 84.5% of initial values after 28 days. Blood pressure decreased significantly and remained low for 24 hours after dosing. The drug was well tolerated in all patients. It is concluded that a single 5 mg dose of ramipril was effective in inhibiting plasma ACE activity and lowering blood pressure in patients with renal failure. There was a slower decline in ramiprilat concentrations compared with subjects with normal renal function.