TY - JOUR T1 - Effect of enterohepatic circulation on the pharmacokinetics of diflunisal in rats. JF - Drug Metabolism and Disposition JO - Drug Metab Dispos SP - 321 LP - 326 VL - 13 IS - 3 AU - J H Lin AU - K C Yeh AU - D E Duggan Y1 - 1985/05/01 UR - http://dmd.aspetjournals.org/content/13/3/321.abstract N2 - The purpose of this study was to examine the effect of enterohepatic circulation on the pharmacokinetics of diflunisal in rats. The "linked animals" experiments provided evidence that diflunisal exhibits an enterohepatic circulation. Within 26 hr after iv administration of diflunisal (10 mg/kg) to rats, excretion was as follows: 42.2% of the dose, bile; 2.3%, unchanged drug; 27.8%, ester glucuronide; and 12.1%, ether glucuronide. On the average, approximately 65% of the amount of the drug and its glucuronides excreted in bile was reabsorbed from the gut. Biliary excretion and plasma data showed that biotransformation of diflunisal to its glucuronides is the rate-limiting step in their elimination. A concentration-dependent decrease in the partial formation clearance to ester glucuronide was observed with decreased concentration of diflunisal. These concentration-dependent kinetics can be at least partly explained by the nonlinear protein binding of diflunisal. ER -