We have studied the pharmacokinetics of
bendazac and its major metabolite,
5-hydroxybendazac, in 11 patients with
hepatic cirrhosis after the
oral administration of a single 500 mg
tablet of
bendazac-lysine, and compared them with those obtained from 10 healthy adults. The rate of absorption of
bendazac, as assessed by tmax and Cmax, is similar in patients and in healthy subjects. The
drug is eliminated mostly by metabolism in healthy adults, more than 60% of the dose being excreted in the urine as
5-hydroxybendazac and its
glucuronide.
Hepatic insufficiency impairs this metabolism, a two-fold decrease in apparent plasma clearance (CL/f) being observed in the patients. Although the plasma unbound fraction of
bendazac is increased in patients (the
drug is highly bound to
plasma albumin), the apparent volume of distribution (V/f) is unchanged. In consequence, the half-life of
bendazac is increased two-fold in the patients. Impairment of metabolism decreases the formation of
5-hydroxybendazac, but metabolism remains the main route of its elimination. Renal excretion of
bendazac accounts for about 10% of the dose in both patients with
cirrhosis and healthy subjects. We conclude that in patients with severe
hepatic insufficiency the daily dose of
bendazac-lysine should be halved.