Effect of uremia and anephric state on the pharmacokinetics of sulindac and its metabolites in rats. II. Differential effects on the biliary excretion.

The differential effects of experimental uremia and surgical anephric state on the biliary excretion of sulindac and its metabolites in rats were investigated. After concurrent administration of 14C-sulindac and 3H-sulfide (5 mg-eq/kg iv), the apparent biliary clearance of sulindac was significantly decreased in anephric rats relative to control rats, whereas the apparent biliary clearance of sulfide was increased in uremic rats as compared to that in control rats. There was a strong positive correlation between the irreversible elimination of sulindac (CLox) and the apparent biliary clearance (r = 0.942). Similarly, the irreversible elimination of sulfide (CLide) was positively correlated with the apparent biliary clearance of sulfide (r = 0.961). A partial explanation is thus provided for differences in the respective effects of uremic and anephric state upon observed CLox and CLide.