Effects in Healthy Subjects of a New Non-Thiol-Containing Angiotensin-Converting Enzyme Inhibitor, Enalapril Maleate (MK-421)

Abstract

1. Single doses of enalapril maleate, ranging from 2.5 to 20 mg, were given orally to 12 normotensive volunteers to determine tolerability, activity on the various components of the renin-angiotensin-aldosterone system and initial pharmacokinetics. 2. Enalapril was rapidly absorbed and maximum plasma concentrations of the diacid, the active metabolite of enalapril, occurred at 3–6 h after dosing. 3. Enalapril significantly decreased systolic blood pressure at 4–6 h after the drug and diastolic blood pressure at 3–6 h after the drug. The maximum decrease of systolic blood pressure was observed at 3–4 h, whereas the maximum decrease of diastolic blood pressure was observed at 6 h. 4. Plasma angiotensin-converting enzyme activity was significantly reduced at all doses. The reduction persisted through 24 h after dosage. Plasma renin activity significantly increased after doses of 5 mg and 20 mg. Aldosterone levels significantly decreased after doses of 10 mg and 20 mg. 5. There were no adverse clinical experiences or abnormal laboratory values noted.