Dependence of the biliary excretion of iopanoic acid on bile salts

Abstract

Iopanoic acid is an iodinated organic acid used extensively as a radiographic contrast material for oral cholecystography. Like bilirubin, it is conjugated predominately with glucuronic acid in the liver, and the biliary excretion is enhanced by the concomitant biliary excretion of bile salts. The extent to which iopanoate excretion in bile is dependent upon bile salt excretion was investigated in unanesthetized bile fistula dogs. The biliary excretion of iopanoate was studied at four different rates of bile salt excretion in separate experiments produced by interruption of the enterohepatic circulation without bile salt infusion and by infusing sodium taurocholate at three constant rates (0.48, 1.87, and 3.21 μmoles per min per kg). Iopanoic acid was infused in stepwise increasing rates in each of the four groups of experiments. The maximum excretion of iopanoate into bile (Emax) was derived from a computer fit of the relation between the biliary excretion rate and plasma concentration of iopanoate for each of the four rates of bile salt excretion. The calculated Emax was closely linked to the rate of bile salt excretion. The Emax increased in an apparent linear manner from 0.20 to 2.36 μmoles per min per kg as the rate of bile salt excretion increased from 0.21 to 2.62 μmoles per min per kg. From the slope of the relation between the biliary excretion of bile salts and the Emax of iopanoate, it could be determined that 0.89 μmole of iopanoate was coupled with each μmole of bile salt. However, at low plasma concentrations of iopanoate (less than approximately 0.06 μmole per ml) when maximum transport of the compound was not obtained, increasing rates of taurocholate infusion did not affect the biliary excretion of iopanoate.