Metabolism of iso-bile acids in the rat.

Iso-bile acids, the BP-hydroxy epimers of the normally occurring bile acids, are commonly found in the feces of man and other animals but are not present in the bile. Since isochenodeoxycholic acid and isoursodeoxycholic acid were recently isolated from the feces of patients treated with chenodeoxycholic acid or ursodeoxycholic acid, the intestinal absorption and hepatic metabolism of [24-‘4C]isochenodeoxycholic acid, [3a-3H]isoursodeoxycholic acid, and their taurine conjugates were studied in rats with biliary or portal blood diversion. Bile acids were isolated from bile, feces, and portal blood, and their radioactivity and quantity were determined by scintillation spectroscopy, thin layer chromatography, and gas-liquid chromatography. After intraduodenal or intracecal infusion of the labeled iso-bile acids, 80 to 90% of the radioactivity was recovered in the bile during 5 h. However, all the label was excreted with the normally occurring 3a-hydroxy bile acid, chenodeoxycholic acid or ursodeoxycholic acid, and only trace amounts of iso-bile acids were detected in the bile. In contrast, when portal blood and feces were examined, label was found only in the 3/lepimer that was infused. Our findings show that isochenodeoxycholic acid, isoursodeoxycholic acid, and their taurine conjugates are well absorbed from both the small and large intestine of the rat and are transported unchanged via the portal blood to the liver. Both iso-bile acids undergo hepatic transformation to their corresponding 3cY-hydroxy epimers during hepatic passage. Thus, the absence of iso-bile acids from the bile results from hepatic transformation rather than from impaired absorption or intestinal conversion.