The influence of hepatic disease on the pharmacokinetics of the new
ACE inhibitor,
benazepril hydrochloride, was evaluated in 12 male patients suffering from
liver cirrhosis. The patients received a single oral 20 mg dose. The plasma concentrations and urinary excretion of unchanged
benazepril and its active metabolite
benazeprilat were determined. Compared with a historical control group of healthy volunteers treated with the same
benazepril. HC1 dose, the plasma concentrations of
benazepril were doubled in the cirrhotic patients. However, the time to reach maximum concentration (0.5 h) was not affected. The plasma kinetics and the urinary excretion of the metabolite
benazeprilat were not significantly altered: Area under the curve and maximum concentration as well as time to maximum concentration (1.5 h) were comparable with those in the healthy subjects. There was also no significant difference between the two populations for the total urinary excretion and the renal clearance of
benazeprilat. Both
benazepril and
benazeprilat were highly bound to
serum proteins (96 and 94 per cent, respectively). In conclusion, the rate and the amount of bioactivation of the inactive
prodrug benazepril to the active
benazeprilat were virtually unaffected by
hepatic cirrhosis. Thus, there seems to be no need for dosage adjustment of
benazepril hydrochloride in patients suffering from
cirrhosis of the liver.