Metabolism of Ursodeoxycholic Acid in Man

Abstract

The metabolism of ursodeoxycholic acid was investigated in 7 subjects during treatment with ursodeoxycholic acid, 1 g per day and chenodeoxycholic acid, 1 g per day for 2 weeks. The molar proportions of biliary cholesterol, lecithin, and bile salts were determined before and during bile acid treatment and the pool sizes and daily turnover of ursodeoxycholic acid were measured by isotope dilution techniques after administration of [24-14C]ursodeoxycholic acid. Ursodeoxycholic acid became the major biliary bile acid (56%) during ursodeoxycholic acid treatment while the proportions of chenodeoxycholic acid declined from 32 to 18%, and cholic acid from 38 to 17%. Deoxycholic acid and lithocholic acid were virtually absent from the bile. During chenodeoxycholic acid administration, chenodeoxycholic acid became the major biliary bile acid (59%), cholic acid declined to 22% of the biliary bile acids, while the proportion of lithocholic acid rose from 1.3 to 3.4%, and an additional 4% were sulfated. Ursodeoxycholic acid increased to 8% of the total bile acids. The molar percent of biliary cholesterol decreased from 8 to 5% during both ursodeoxycholic acid and chenodeoxycholic acid administration. After [24- 14C]ursodeoxycholic acid was administered intravenously the biliary specific activity- time curves of ursodeoxycholic acid decayed exponentially during both bile acid treatment periods. In the ursodeoxycholic acid-treated subjects, the ursodeoxycholic acid decay curve intersected with the rising specific activity curve of chenodeoxycholic acid and revealed a precursor-product relationship. The average ursodeoxycholic acid pool measured 938 ± 458 mg with a daily production rate of 900 ± 438 mg per day (absorption). The average ursodeoxycholic acid pool during chenodeoxycholic acid treatment measured 123 ± 82 mg and the production rate was 91 ± 35 mg per day (synthesis). These studies demonstrate that substantial quantities of ursodeoxycholic acid are absorbed when this bile acid is fed or are synthesized when chenodeoxycholic acid is given. The reduction in bile lithogenicity during ursodeoxycholic acid administration implies that this bile acid like chenodeoxycholic acid may be effective in dissolving cholesterol gallstones in man.