[The effect of clanobutin on bile excretion in rat and dog (author's transl)].

The effect of 4-[p-chloro-N-(p-methoxyphenyl)-benzamido] butyric acid (clanobutin, Bykahepar) on bile formation was studied in anesthetized male Sprague-Dawley rats and in non-anesthetized female boxer dogs. Following i.v. injection of 40 mg/kg body weight of clanobutin, a marked choleresis paralleling the biliary excretion of the drug was observed in both species. The biliary elimination of 1 mumol clanobutin (and metabolites) caused on the average an increment of bile flow of 90 microliter and 11.5 microliter in the rat and dog, respectively. Bile flow was linearly related to clanobutin excretion in rat and dog. Within the period of observation 55% of the dose of clanobutin in the rat, and 80% of the dose in the dog were eliminated via the bile; urinary excretion amounted to 3% of the dose. In rat bile, 32% of the clanobutin was present as the parent compound; the remaining 68% consisted of 3 metabolites. Measurement of the erythritol clearance in the dog suggests that clanobutin stimulates the bile salt-independent, canalicular bile formation. In addition, however, the observed changes in the bile/plasma concentration ratio of erythritol, as well as a predominant excretion of bicarbonate and chloride point to a possible ductular effect of clanobutin. In these acute studies, the drug did not influence the bile salt, phospholipid or cholesterol excretion. Cholesterol saturation of bile was unaffected.