Rapid conversion of the new angiotensin converting enzyme inhibitor ramipril to its active metabolite in rats.

The rate of conversion of ramipril (Hoe 498), a new angiotensin converting enzyme (ACE) inhibitor, to its active metabolite was compared with that of enalapril. After intravenous administration to rats, ramipril was very rapidly deesterified to its active moiety, ramiprilat. The ratio of the active metabolite level to the prodrug level in plasma at 5 min after administration was 10.7 for ramipril, which was about 5 times the ratio for enalapril. The in vitro conversion rates of ramipril were higher than those of enalapril in all rat tissue homogenates examined, including the liver, a main site of metabolism. The apparent Km values of ramipril and enalapril in the liver were 190 and 710 mumol/l, respectively, suggesting that ramipril has a higher affinity for esterase than enalapril. In conclusion, ramipril was superior to enalapril in efficiency of conversion to the active metabolite.