THE EFFECT OF EXPERIMENTAL RENAL FAILURE ON TOLFENAMIC ACID DISPOSITION IN THE DOG

✍ Scribed by HERVÉ P. LEFEBVRE; VALÉRIE LAROUTE; MICHEL ALVINERIE; MARC SCHNEIDER; PATRICK VINCLAIR; JEAN-PIERRE BRAUN; PIERRE-LOUIS TOUTAIN

• Publisher: John Wiley and Sons
• Year: 1997
• Tongue: English
• Weight: 692 KB
• Volume: 18
• Category: Article
• ISSN: 0142-2782
• DOI: 10.1002/(sici)1099-081x(199701)18:1<79::aid-bdd34>3.0.co;2-f

✦ Synopsis

The pharmacokinetic disposition of tolfenamic acid, an NSAID, after a single administration of tolfenamic acid (4 mg kg 71 ) by the intravenous (IV) route was compared in eight dogs before and after a surgically induced renal failure. Renal impairment was con®rmed by a signi®cant increase ( p50´001) of water intake, urine volume, and urea and creatinine plasma concentration. PAH and inulin clearances decreased after surgery from 15´2+4´2 to 9´5+0´8 mL kg 71 min 71 ( p50´05) and from 4´37+1´15 to 2´43+0´88 mL kg 71 min 71 ( p=0´067), respectively. After surgery, clearance of TA was signi®cantly ( p50´001) increased, from 2´22+1´68 to 3´59+1´81 mL kg 71 min 71 . There was no modi®cation of the steady-state volume of distribution ( p40´05) and the mean residence time was signi®cantly decreased from 606+199 to 373+302 min ( p50´05). No variation of binding to plasma proteins (599%) was observed. These results suggest that renal insuciency could increase hepatic metabolism and/or alter the enterohepatic cycle of TA.