Pharmacokinetics of bendazac-lysine and 5-hydroxybendazac in patients with renal insufficiency.
The pharmacokinetics of bendazac and its major metabolite, 5-hydroxybendazac, have been investigated in 15 patients with moderate to severe renal insufficiency and renal failure following a single oral dose of 500 mg bendazac-lysine. The pharmacokinetic parameters were compared to those obtained in 10 healthy adult volunteers. The rate and the extent of absorption of bendazac was not modified in the patients with moderate and severe renal insufficiency, nor was there any change in plasma tmax, Cmax, apparent elimination t1/2 and AUC. There was a significant increase in the unbound fraction of bendazac in renal failure patients undergoing haemodialysis, with a consequent increase in the apparent volume of distribution (V/F) and apparent plasma clearance (CL/F), and a decrease in plasma Cmax and AUC. Simultaneous changes of V/F and CL/F lead to an unchanged plasma t1/2 in these patients. Renal clearance (CLR) was decreased, but CL/F was not affected, since renal excretion is a minor route of elimination of bendazac. Bendazac is mostly eliminated by metabolism to 5-hydroxybendazac, in healthy subjects greater than 60% of a dose being excreted in urine as 5-hydroxybendazac and its glucuronide. In patients with renal insufficiency urinary excretion of 5-hydroxybendazac was decreased and the systemic availability of the metabolite (AUC), was increased about three-fold, irrespective of the degree of renal failure. Plasma 5-hydroxybendazac glucuronide accumulated according to the degree of renal insufficiency. Overall it can be assumed that the pharmacological effect of the drug will not be enhanced in renal failure and that the dosage regimen of bendazac-lysine in such patients need not be modified.
Rovei
V
V
Centre de Recherche Delalande, Rueil Malmaison, Toulouse, France.
Campistron
G
G
Dueymes
J M
JM
Ego
D
D
Conte
J J
JJ
Houin
G
G
D000328:Adult; D000368:Aged; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000493:pharmacokinetics*; D001682:Biological Availability; D001798:Blood Proteins / Q000378:metabolism; D005260:Female; D006801:Humans; D007191:Indazoles / Q000493:pharmacokinetics*; D007676:Kidney Failure, Chronic / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D011485:Protein Binding; D011720:Pyrazoles / Q000493:pharmacokinetics*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D001798:Blood Proteins; D007191:Indazoles; D011720:Pyrazoles; C051605:5-hydroxybendazac; C036067:bendazac lysine