Article: PDF OnlyEvaluation of Angiotensin Converting Enzyme (ACE) in the Pharmacokinetics and Pharmacodynamics of ACE InhibitorsJohnston, C. I.; Jackson, B.; Cubela, R.; Larmour, I.; Arnolda, L.Author Information Monash University Department of Medicine, Prince Henry's Hospital, Melbourne, Victoria, Australia Journal of Cardiovascular Pharmacology: Volume 8 - Issue - p S9-S14 Free Abstract The increasing number of angiotensin converting enzyme (ACE) inhibitors means that compounds with different enzyme kinetics, pharmacokinetics, bioavailability, and pharmacodynamics will appear. They will, however, all inhibit ACE, and their hypotensive effect will be a consequence of this action. Enalapril (MK-421) is an esterified prodrug, which in man is converted by the liver to the bioactive potent ACE inhibitor enalaprilat (enalaprilic acid, MK-422). This probably accounts for the slower plasma appearance of MK-422 and the longer duration of action of enalapril. The clinical significance of deesterification by the liver needs further study but minor abnormalities of liver function, such as occur in congestive heart failure, do not affect the rate of deesterification and hence the plasma enalaprilat levels. A close relationship between the plasma drug level, degree of ACE inhibition, and the hormonal and hypotensive effect can be demonstrated after both acute and chronic enalapril administration to hypertensive patients. Chronic therapy with enalapril leads to induction of ACE but in humans this is not sufficient to lead to resistance or tolerance to the drug. Enalapril offers an exciting new approach to the treatment of hypertension with some distinct advantages over conventional antihypertensive therapy. © Lippincott-Raven Publishers.