Lithocholate metabolism during chemotherapy for gallstone dissolution. 2. Absorption and sulphation

Abstract

The amount of lithocholate input and the size of the total lithocholate exchangeable pool were measured using isotope dilution in three patients ingesting chenodeoxycholic acid for gallstone dissolution and two healthy control subjects. Because the specific activity decay curve was biexponential in appearance, input was calculated using a stochastic analysis employing the Stewart-Hamilton equation. By this method, the lithocholate input and the size of the exchangeable pool in gallstone patients during chenic acid ingestion was four to five times that observed in the healthy control subjects. It was calculated that about one-fifth of the newly formed lithocholate was absorbed in both gallstone patients and healthy control subjects. The extent of sulphation of absorbed lithocholate was then measured in seven gallstone patients whto had been ingesting chenodeoxycholic acid for gallstone dissolution by defining the chemical form of radioactivity in bile after intravenous administration of labelled lithocholate. Similar studies were carried out in eight healthy control subjects, but, in addition the extent of sulphation of injected lithocholylglycine and lithocholyltaurine was also defined. When lithocholate was injected, the majority of radioactivity in bile (50-60%) was present as sulphated conjugates, both in gallstone patients and healthy control subjects. The degree of sulphation was greater for glycine than taurine conjugates, and these findings, which suggested preferential sulphation of the glycine conjugates of lithocholate, were confirmed by showing that injected lithocholylglycine was sulphated to a much greater extent than injected lithocholyltaurine. These findings indicate that in patients receiving chenic acid there is effective sulphation of lithocholate, especially its glycine conjugates, despite a considerable increase in lithocholate absorption; they may provide an explanation for the lack of hepatotoxicity of chenic acid in man.