When dialysis was started two hours after ingestion of 10 mg of benazepril, approximately 6% of benazeprilat was removed in 4 hours of dialysis. The parent compound, benazepril, was not detected in the dialysate. The disposition of benazepril and benazeprilat in patients with mild-to-moderate renal insufficiency (creatinine clearance > 30 mL/ min) is similar to that in patients with normal renal function. In patients with creatinine clearance 30 mL/ min, peak benazeprilat levels and the initial (alpha phase) half-life increase, and time to steady state may be delayed (see DOSAGE AND ADMINISTRATION). 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. In patients with renal failure, biliary clearance may compensate to an extent for deficient renal clearance. In patients with hepatic dysfunction due to cirrhosis, levels of benazeprilat are essentially unaltered. The pharmacokinetics of benazepril and benazeprilat do not appear to be influenced by age. In studies in rats given 14 C-benazepril, benazepril and its metabolites crossed the blood-brain barrier only to an extremely low extent. Multiple doses of benazepril did not result in accumulation in any tissue except the lung, where, as with other ACE inhibitors in similar studies, there was a slight increase in concentration due to slow elimination in that organ. Some placental passage occurred when the drug was administered to pregnant rats. Pharmacodynamics Single and multiple doses of 10 mg or more of Lotensin cause inhibition of plasma ACE activity by at least 80%-90% for at least 24 hours after dosing. Pressor responses to exogenous angiotensin I were inhibited by 60%-90% (up to 4 hours post-dose) at the 10-mg dose. | ||||
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