The influence of hepatic cirrhosis on the pharmacokinetics of benazepril hydrochloride.
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.
Kaiser
G
G
Research and Development Department, Ciba-Geigy Ltd, Basle, Switzerland.
Ackermann
R
R
Gschwind
H P
HP
James
I M
IM
Sprengers
D
D
McIntyre
N
N
Defalco
A
A
Holmes
I B
IB
D000328:Adult; D000368:Aged; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000493:pharmacokinetics*; D001552:Benzazepines / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics* / Q000652:urine; D001798:Blood Proteins / Q000378:metabolism; D006801:Humans; D008103:Liver Cirrhosis / Q000097:blood* / Q000652:urine; D008297:Male; D008875:Middle Aged
D000806:Angiotensin-Converting Enzyme Inhibitors; D001552:Benzazepines; D001798:Blood Proteins; C052133:benazeprilat; C044946:benazepril