Synthesis and metabolism of sodium 3α,7α‐dihydroxy‐25,26‐bishomo‐5β‐cholane‐26‐sulfonate in the hamster

This paper reports the chemical synthesis of a new bile acid analogue, namely sodium 3α,7α‐dihydroxy‐25,26‐bishomo‐5β‐cholane‐26‐sulfonate (bishomoCDC‐sul) from chenodeoxycholic acid and describes its metabolism in the hamster. The structure of the new compound was confirmed by proton and carbon‐13 nuclear magnetic resonance spectroscopy. After intravenous infusion of [3H]‐labeled sulfonate into bile fistula hamsters, it was extracted by the liver and secreted into the bile; more than 65% of the radioactivity was recovered in the bile within 1 h. Following intraduodenal administration of the [3H]sulfonate and [14C]chenodeoxycholyltaurine, both compounds were excreted into the bile more slowly; only 41 and 43% of the radioactivity, respectively, were recovered in the bile during the four‐hour experimental period. In contrast, when the labeled compounds were injected into the terminal ileum, both the sulfonate and chenodeoxycholyltaurine were repidly absorbed and secreted into the bile; 84 and 97%, respectively, of the radioactivity were recovered during a four‐hour period. Chromatographic analysis demonstrated that in these short‐term experiments most (>95%) of the sulfonate was secreted into the bile without biotrasformation regardless of the route of administration. When infused intravenously at increasing doses, bishomoCDC‐sul induced cholestasis at an infusion rate of 1 μmol/min/kg. These results suggest that sodium 3α,7α‐dihydroxy‐25,26‐bishomo‐5β‐cholane‐26‐sulfonate was absorbed from the terminal ileum by active transport, extracted by the liver, and secreted into the bile in a manner similar to that of the natural bile acids.