Metabolism of lithocholate in healthy man. III. Plasma disappearance of radioactivity after intravenous injection of labeled lithocholate and its derivatives.

The plasma disappearance of intravenously injected radiolabeled lithocholate, lithocholylglycine, and their respective 3alpha-sulfates was defined in healthy subjects. Binding of these bile acids to serum protein in vitro was measured by ultrafiltration. Lithocholate and lithocholylglycine rapidly disappeared from plasma (t1/2 less than 3 min), showing a behavior similar to that of the other major primary bile acids present in man. However, after 15 min, when 99% of the radioactivity had been cleared, the disappearance curve flattened, and chromatography suggested that the chemical form of circulating radioactivity had become sulfolithocholylglycine, the end product of hepatic metabolism of lithocholate in man. Injected sulfolithocholate and sulfolithocholylglycine were cleared about one-fourth as rapidly. Lithocholate and its derivatives were tightly bound to serum proteins (87 to 99%); for a given steroid moiety and mode of conjugation, binding was altered slightly by sulfation, but all sulfated derivatives were tightly bound (greater than 95%) to serum protein. The results indicate that lithocholate, which enters the plasma compartment, whether unconjugated, conjugated, or conjugated and sulfated, will be protein-bound but nonetheless will be rapidly cleared from plasma.