Pharmacokinetics, converting enzyme inhibition and peripheral arterial hemodynamics of ramipril in healthy volunteers.

The effects of a 10 mg dose of ramipril, a new angiotensin I converting enzyme (ACE) inhibitor, on systemic blood pressure, heart rate, brachial artery blood flow, brachial artery diameter, carotid artery blood flow, carotid artery diameter, forearm vascular resistance, plasma ACE and renin activities and plasma aldosterone were investigated. Ramipril's effects in 6 healthy volunteers on a normal sodium diet were compared with those of placebo over a 24-hour period after oral drug intake in an open cross-over trial. Ramipril inhibited plasma ACE activity, an effect that peaked at 3 to 4 hours and persisted up to at least 24 hours. Plasma renin activity increased from 4 to 12 hours after drug intake and plasma aldosterone was slightly decreased. Systemic blood pressure in the supine position was slightly decreased between 6 and 8 hours after drug intake but heart rate remained unaffected. Ramipril significantly increased brachial artery blood flow, brachial artery diameter and carotid artery blood flow and decreased forearm vascular resistance between 3 and 8 hours after drug administration. These peripheral arterial vasodilating effects were more marked in the muscular resistance vessels and affected both large arteries and arterioles in the brachial vascular territory. A correlation was found between the log of plasma concentrations of ramipril diacid metabolite and the drug-induced plasma ACE activity inhibition and increase in brachial artery blood flow. There was also a correlation between these 2 latter effects. A plasma ACE activity inhibition of 80% was required to induce significant increases in brachial artery blood flow and carotid artery blood flow.

RCT Entities:   Population Interventions Outcomes