Tolerance and pharmacodynamics of the angiotensin converting enzyme inhibitor 2-[N-[(S)-1-ethoxycarbonyl-3-phenylpropyl]-L-alanyl]-(1S,3S,5S)-2- azabicyclo[3.3.0]octane-3-carboxylic acid (Hoe 498) in healthy volunteers

Abstract

In healthy volunteers a single oral dose of 5 mg 2-[N-[(S)-1-Ethoxycarbonyl-3-phenylpropyl]-L-alanyl]-(1S,3S, 5S)-2-azabicyclo[3.3.0]octane-3-carboxylic acid (Hoe 498) was well tolerated. Following 5 mg Hoe 498 plasma angiotensin converting enzyme (ACE) activity was inhibited by almost 100% up to 8 h. A marked effect on plasma ACE was observed for more than 8 days. Plasma renin activity increased whereas aldosterone plasma levels decreased only slightly. Sodium and potassium excretion was not influenced by the compound. Systolic and diastolic blood pressure was slightly lowered by Hoe 498, whereas no relevant changes in pulse rate were observed.