Molecule

Drug Groups

approved; investigational

Description

Benazepril, brand name Lotensin, is a medication used to treat high blood pressure (hypertension), congestive heart failure, and chronic renal failure. Upon cleavage of its ester group by the liver, benazepril is converted into its active form benazeprilat, a non-sulfhydryl angiotensin-converting enzyme (ACE) inhibitor.

Indication

For the treatment of hypertension. It may be used alone or in combination with thiazide diuretics.

Pharmacology

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.

Toxicity

Most likely symptom of overdosage is severe hypotension. Most common adverse effects include headache, dizziness, fatigue, somnolence, postural dizziness, nausea, and cough.

Affected Organisms

Biotransformation

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.

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.

Half Life

10-11 hours

Protein Binding

benazepril, 97%; benazeprilat, 95%

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.

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]

References

External Links