| Indication |
For the treatment of hypertension. It may be used alone or in combination with thiazide diuretics. |
| Pharmacodynamics |
Benazepril, an angiotensin-converting enzyme (ACE) inhibitor, is
a prodrug which, when hydrolyzed by estarases to its active
Benazeprilat, is used to treat hypertension and heart failure, to reduce
proteinuria and renal disease in patients with nephropathies, and to
prevent stroke, myocardial infarction, and cardiac death in high-risk
patients. Benazepril and Benazeprilat inhibit angiotensin-converting
enzyme (ACE) in human subjects and animals. ACE is a peptidyl
dipeptidase that catalyzes the conversion of angiotensin I to the
vasoconstrictor substance, angiotensin II. Angiotensin II also
stimulates aldosterone secretion by the adrenal cortex. |
| Mechanism of action |
Benazeprilat, the active metabolite of Benazepril, competes with
angiotensin I for binding at the angiotensin-converting enzyme, blocking
the conversion of angiotensin I to angiotensin II. Inhibition of ACE
results in decreased plasma angiotensin II. As angiotensin II is a
vasoconstrictor and a negative-feedback mediator for renin activity,
lower concentrations result in a decrease in blood pressure and
stimulation of baroreceptor reflex mechanisms, which leads to decreased
vasopressor activity and to decreased aldosterone secretion.
Benazeprilat may also act on kininase II, an enzyme identical to ACE
that degrades the vasodilator bradykinin. |
| Absorption |
Peak in plasma within 0.5-1.0 hours. The extent of absorption is
at least 37% as determined by urinary recovery and is not significantly
influenced by the presence of food in the GI tract. |
| Volume of distribution |
Not Available |
| Protein binding |
benazepril, 97%; benazeprilat, 95% |
| Metabolism |
Cleavage of the ester group (primarily in the liver) converts
benazepril to its active metabolite, benazeprilat. Benazepril and
benazeprilat may be conjugated to glucuronic acid prior to urinary
excretion. |
| Route of elimination |
Benazepril and benazeprilat are cleared predominantly by renal
excretion in healthy subjects with normal renal function. Nonrenal
(i.e., biliary) excretion accounts for approximately 11%-12% of
benazeprilat excretion in healthy subjects. |
| Half life |
10-11 hours |
| Clearance |
- 0.35 L/hr/kg [pediatric hypertensive patients receiving multiple daily doses of Benazepril hydrochloride 0.1 – 0.5 mg/kg]
- 0.13 L/hr/kg [healthy adults receiving a single dose of 10 mg]
|
| Toxicity |
Most likely symptom of overdosage is severe hypotension. Most
common adverse effects include headache, dizziness, fatigue, somnolence,
postural dizziness, nausea, and cough. |
