The role of bile salts in the hepatic excretion of iopanoic acid.

Abstract

Previous studies on the pharmacokinetics of iopanoic acid (Telepaque) have shown that there is a direct relationship between the biliary excretion of iopanoic acid and canalicular bile flow produced by bile salts (sodium taurocholate). The object of the present investigation is to determine if this association is due to an effect of canalicular bile flow per se or due to a direct action of bile salts. The role of micelle formation by bile salts in the transport process is also evaluated. Iopanoic acid excretion in bile was studied during choleresis produced by SC2644 (a compound which stimulates bile-salt independent canalicular bileflow), with sodium dehydrocholate (a bile salt which increases bile-salt dependent bile flow, but does not form micelles) and with sodium taurocholate (a micelle-forming bile-salt choleretic). Experiments were performed in both anesthetized dogs with a catheter placed in the common duct immediately prior to the experiment, and in nonanesthetized dogs prepared months earlier with a Thomas cannula inserted into the duodenum. The results show that the amount of iopanoic acid excreted in the bile rises in proportion to the increase in bile flow stimulated by dehydrocholate and taurocholate, but the total excretion remains unchanged by choleresis produced by SC2644. Failure of SC2644 to increase the excretion of iopanoic acid despite an increase in bile flow indicates that the canalicular bile flow per se is not the important determinant regulating iopanoic acid excretion. Because bile salts stimulate iopanoic acid excretion, it is the bile salts themselves and not the increase in bile flow that influence iopanoic acid. Since the experiments show no difference between the effect of dehydrocholate and taurocholate, it is not the micellar property of bile salts that enables these compounds to increase the rate of excretion of iopanoic acid. It is postulated that there is an allosteric interaction between bile salts and the carrier for iopanoic acid in the canalicular membrane which facilitates the transport of iopanoic acid from the hepatocyte into the bile.