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

<jats:p>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.</jats:p> <jats:p>2. Enalapril was rapidly absorbed and maximum plasma concentrations of the diacid, the active metabolite of enalapril, occurred at 3–6 h after dosing.</jats:p> <jats:p>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.</jats:p> <jats:p>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.</jats:p> <jats:p>5. There were no adverse clinical experiences or abnormal laboratory values noted.</jats:p>