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 enalaprilate (
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.