Chenodeoxycholic acid, radioactive

Measurement of fecal excretion of isotopic bile acids (65) gives only the half-life of the labeled bile acid used. The isotope is injected intravenously, and the daily fecal excretion of radioactivity is measured. According to this procedure, the fractional excretion rate of cholic acid in man is normally about 12-13% per day (66,67). Disadvantages of the method are that the absolute values are not obtained, the cholic and chenodeoxycholic acid excretions must be measured separately or a double label method must be used, and the fecal flow should be regular, though an unabsorbable fecal marker can be used. The method appears to be suitable for screening of ileal dysfunction. 

Palmer [56-58] first reported the presence in human bile of a sulfate ester of lithocholate in as much as 40-80% of the small amounts of available glyco- and taurolithocholate. Following intragastric or intraduodenal intubation of glyco-[24- C]lithocholic acid 3-sulfate to rats with bile fistulas, 70-89% of the radioactivity was recovered in bile [59] allolithocholate 3-sulfate was also reported in rat bile [60]. The radioactive conjugate was absorbed intact without loss of the sulfate, and was not metabolized in the liver (e.g., to the muricholates or chenodeoxycholate) [58,59]. Similarly, chenodeoxycholate 3-sulfate was not metabolized after intravenous infusion into rats or hamsters with or without obstruction of the biliary tract [58,59,61]. Lithocholate 3-sulfate is efficiently removed from the body [62]. 

Urinary excretion of bile salts by healthy subjects is apparently very limited. The urine contained 2 % of the radioactivity administered orally as i C-cholic acid to a healthy subject in whom 100% of the radioactivity was recovered (80) and 0.12% of radioactivity administered to four normal subjects when i C-cholate was given intravenously (25). Conventional methods do not detect bile salts in the urine of healthy subjects (81,82). In jaundice patients, however, bile salts are excreted in the urine regularly (83). The highest 24-hr excretion rates reported by Gregg occurred in patients with common bile duct obstruction (58 mg/24 hr) and drug-induced cholestasis (40 mg/24 hr). The cholate/chenodeoxycholate ratio was greater than 0.59... 

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