Metabolism and time-course excretion of murideoxycholic acid, a 6β-hydroxylated bile acid, in humans

The metabolism and time-courses of urinary and fecal excretions of murideoxycholic acid (MDCA; 3α,6β-dihydroxy-5β-cholanoic acid), a 6β-hydroxylated bile acid, was investigated in man. The study was carried out in two groups of subjects. Six cholecystectomized patients fitted with a cystic duct drain ingested 100 mg of a tracer dose of 3H-MDCA. Time-course of radioactivity in plasma was then followed for an 8-h period. Biliary, urinary and fecal excretions of radioactivity were measured for a 5-day period and excreted MDCA metabolites were identified. Five lithiasic patients with intact enterohepatic circulation ingested 500 mg of the same tracer dose of 3H-MDCA. Radioactivity in plasma was followed for a 49-h period and urinary and fecal excretions of radioactivity were measured daily for 7 days. In the first group, the excretion of the radioactivity by the three routes (bile+urine+feces) reached 97.8±1.5% of the ingested dose but dropped to 75±8.3% (urine+feces) in patients in the second group. In cholecystectomized patients, the estimation of intestinal MDCA absorption was dependent on cystic duct drain flow rate and gave values ranging from 20% to 87%. The biological half-life of MDCA in lithiasic patients averaged 3.4±0.7 days. Radioactivity appeared in the plasma in the first hour and reached a maximum 6 and 3 h after the beginning of the experiment in group I and II respectively. In the second group, another peak of radioactivity in plasma was observed just after breakfast. Analysis of biliary metabolites of MDCA showed the presence only of glyco- and tauro-congugates of this bile acid. Urinary excretion of radioactivity was low in all patients and MDCA was recovered as glyco- and sulfo-glyco-MDCA. It was eliminated in feces as MDCA without dehydroxylation or oxidation. Despite an unusual 6β-hydroxyl group, MDCA was absorbed by the intestine, taken up by the liver, conjugated to glycine and taurine, and stored in the gallbladder during fasting. It was metabolized by the liver as an endogenous bile acid. After acute administration of MDCA, its hydroxyl groups were not oxidized or dehydroxylated by intestinal bacterial enzymes. Poorly eliminated in urine, it remained in the enterohepatic circulation for the same period as bile acids used in cholelithiasis treatment. The metabolism and time-courses of urinary and fecal excretions of murideoxycholic acid (MDCA; 3α,6β-dihydroxy-5β-cholanoic acid), a 6β-hydroxylated bile acid, was investigated in man. The study was carried out in two groups of subjects. Six cholecystectomized patients fitted with a cystic duct drain ingested 100 mg of a tracer dose of 3H-MDCA. Time-course of radioactivity in plasma was then followed for an 8-h period. Biliary, urinary and fecal excretions of radioactivity were measured for a 5-day period and excreted MDCA metabolites were identified. Five lithiasic patients with intact enterohepatic circulation ingested 500 mg of the same tracer dose of 3H-MDCA. Radioactivity in plasma was followed for a 49-h period and urinary and fecal excretions of radioactivity were measured daily for 7 days. In the first group, the excretion of the radioactivity by the three routes (bile+urine+feces) reached 97.8±1.5% of the ingested dose but dropped to 75±8.3% (urine+feces) in patients in the second group. In cholecystectomized patients, the estimation of intestinal MDCA absorption was dependent on cystic duct drain flow rate and gave values ranging from 20% to 87%. The biological half-life of MDCA in lithiasic patients averaged 3.4±0.7 days. Radioactivity appeared in the plasma in the first hour and reached a maximum 6 and 3 h after the beginning of the experiment in group I and II respectively. In the second group, another peak of radioactivity in plasma was observed just after breakfast. Analysis of biliary metabolites of MDCA showed the presence only of glyco- and tauro-congugates of this bile acid. Urinary excretion of radioactivity was low in all patients and MDCA was recovered as glyco- and sulfo-glyco-MDCA. It was eliminated in feces as MDCA without dehydroxylation or oxidation. Despite an unusual 6β-hydroxyl group, MDCA was absorbed by the intestine, taken up by the liver, conjugated to glycine and taurine, and stored in the gallbladder during fasting. It was metabolized by the liver as an endogenous bile acid. After acute administration of MDCA, its hydroxyl groups were not oxidized or dehydroxylated by intestinal bacterial enzymes. Poorly eliminated in urine, it remained in the enterohepatic circulation for the same period as bile acids used in cholelithiasis treatment.