Direct Measurement of Hepatic Extraction of Chenodeoxycholic Acid and Ursodeoxycholic Acid in Man

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Abstract
1. The hepatic extraction ratios of chenodeoxycholic acid and ursodeoxycholic acid have been measured in 12 patients without, and 20 patients with, liver disease. 2. Ten of the patients without liver disease were studied during cardiac catheterization, with a continuous infusion technique. Two of the patients without liver disease and all those with liver disease received an intravenous bolus of [14C]chenodeoxycholic acid or [14C]ursodeoxycholic acid, during transvenous liver biopsy. 3. The extraction ratio of chenodeoxycholic acid was 0·63 ± 0·03 (mean ± sem) and of ursodeoxycholic acid 0·53 ± 0·01, in the patients without liver disease. In those with mild liver disease, extraction was slightly impaired (chenodeoxycholic acid: 0·49 ± 0·03; ursodeoxycholic acid: 0·43 ± 0·05), whereas in those with more severe liver disease it was greatly reduced (chenodeoxycholic acid: 0·16 ± 0·08; ursodeoxycholic acid: 0·07 ± 0·01). 4. The results suggest that (a) direct measurements confirm the accuracy of indirect estimates of hepatic extraction of chenodeoxycholic acid, (b) hepatic extraction of chenodeoxycholic acid is lower than that of cholic acid and glycocholic acid, but higher than that of ursodeoxycholic acid, (c) progressive impairment of the extraction ratios of these two bile acids occurs as the severity of liver disease increases, and (d) the ratios are correlated with indocyanine green extraction ratios.