Impaired lithocholate sulfation in the rhesus monkey: a possible mechanism for chenodeoxycholate toxicity

Radioactive lithocholate was administered intravenously to female rhesus monkeys with an exteriorized enterohepatic circulation, and the chemical form of biliary radioactivity was defined by thin layer chromatography. Most radioactivity was excreted in bile in the form of unsulfated conjugates (77%), indicating impaired sulfation relative to published data for man. Defective sulfation of lithocholate, the major bacterial biotransformation product of chenodeoxycholic acid, can explain accumulation of lithocholate in the enterohepatic circulation and provide a possible mechanism for the hepatotoxicity observed during chenodeoxycholic acid administration to the nonhuman primate.