The pharmacokinetics of bendazac-lysine and 5-hydroxybendazac, its main metabolite, in patients with hepatic cirrhosis.
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.
Rovei
V
V
Centre de Recherche Delalande, Rueil Malmaison, France.
Escourrou
J
J
Campistron
G
G
Ego
D
D
Thiola
A
A
Ribet
A
A
Houin
G
G
D000328:Adult; D000368:Aged; D001798:Blood Proteins / Q000378:metabolism; D005260:Female; D006801:Humans; D007191:Indazoles / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics* / Q000652:urine; D008103:Liver Cirrhosis / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D011485:Protein Binding; D011720:Pyrazoles / Q000493:pharmacokinetics*
D001798:Blood Proteins; D007191:Indazoles; D011720:Pyrazoles; C051605:5-hydroxybendazac; C036067:bendazac lysine