Abstract

Benazepril is a prodrug that, following rapid conversion to benazeprilat, is a potent nonsulfhydryl inhibitor of angiotensin-converting enzyme. The absorption, bioactivation, distribution, and elimination of benazepril and benazeprilat have been evaluated in healthy subjects, hypertensive patients, and patients with characteristics known to alter the pharmacokinetic disposition of ACE inhibitors, such as renal impairment, hepatic impairment, and advanced age. Following oral administration, benazepril is absorbed and transformed into benazeprilat in the liver. Coadministration of benazepril with food delays absorption slightly but does not affect the ultimate bioavailability of benazeprilat. Severe hepatic impairment slows conversion of benazepril to benazeprilat but does not affect the overall bioavailability of benazeprilat; thus dosage adjustment is not necessary in the hepatically impaired population. Mild-to-moderate renal impairment (creatinine clearance greater than 30 ml/min) slightly increases benazeprilat concentrations; severe renal impairment (creatinine clearance less than 30 ml/min) reduces benazeprilat elimination and requires dosage reduction. In elderly patients, benazepril disposition is the same as in younger patients, although benazeprilat clearance is slightly reduced. No clinically significant drug-drug interactions occur with benazepril and many other medications commonly prescribed to elderly hypertensive patients. The pharmacokinetic characteristics of benazepril are stable over a wide range of conditions, and dosage adjustments for pharmacokinetic reasons are required infrequently.