Validation of Use of 11, 12-2H-Labeled Chenodeoxycholic Acid in Isotope Dilution Measurements of Bile Acid Kinetics in Man

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Abstract
Extract: Chenodeoxycholic acid labeled with 2H in the 11 and 12 positions was prepared by catalytic reduction of δ11–12 unsaturated derivatives of cholic acid. To validate the use of this stable isotope for the determination of bile acid kinetics by isotope dilution, it was administered to seven normal male volunteers simultaneously with [24-14C]chenodeoxycholic acid. Bile was collected at regular intervals over the following 5 days, and the Chenodeoxycholic acid pool size and fractional turnover rate were determined from the specific activity decay curve for 14C and from the isotopic abundance curve for 2H. Estimates of the pool size by both isotopes showed a correlation of r = 0.95 and similar precision. Synthesis rate, the product of pool size and fractional turnover rate, also showed good agreement (r = 0.97), Because previous investigations have shown that bile acids tagged with hydrogen isotopes at the 11 and 12 positions are stable in man, the present data suggest that 11,12-2H-labeled bile acids may be used in place of radioactive isotopes for valid isotopic measurement of bile acid kinetics in healthy infants and children. Speculation: The availability of bile acids labeled with stable isotopes, for example, 2H or 13C, would permit bile acid metabolism to be studied by isotope dilution measurements in any population of patients without radiation hazard.

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