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.