TY - JOUR
T1 - Formation of iso-ursodeoxycholic acid during administration of ursodeoxycholic acid in man
AU - Beuers, U.
AU - Fischer, S.
AU - Spengler, U.
AU - Paumgartner, G.
PY - 1991
Y1 - 1991
N2 - The appearance of iso-ursodeoxycholic acid (isoUDCA; 3 beta,7 beta-dihydroxy-5 beta-cholan-24-oic acid) in serum of patients with chronic cholestatic liver disease and of healthy subjects during administration of ursodeoxycholic acid (UDCA) is reported. Comparison of the mass spectrum of the newly appearing bile acid with that of authentic 3 beta,7 beta-dihydroxy-5 beta-cholan-24-oic acid revealed its identity as the 3 beta-epimer of UDCA. The appearance of 13C-isoUDCA in serum after ingestion of 13C-UDCA proved its product precursor relationship with UDCA. The putative intermediate in the epimerization of UDCA to isoUDCA, 3-oxo-7 beta-hydroxy-5 beta-cholan-24-oic acid, was identified in serum of patients with cholestatic liver disease during treatment with UDCA. Serum concentrations of isoUDCA after 4 weeks of UDCA treatment were 1.37 +/- 0.79 mumol/l (mean +/- S.D.) in eight patients with primary biliary cirrhosis (PBC), 1.25 +/- 0.91 mumol/l in six patients with primary sclerosing cholangitis (PSC) and 3.87 +/- 0.44 mumol/l in four healthy controls. The intestinal bacterial flora as well as microsomal enzymes of the liver may be involved in the epimerization of UDCA to isoUDCA as indicated by decreased serum levels of isoUDCA under antibiotic treatment with doxycycline (100 mg/day) in healthy subjects and a correlation (r = 0.873, p less than 0.001) between the hepatic microsomal function measured by the 14C-aminopyrine breath test and the fractional conversion of applied UDCA to isoUDCA (isoUDCA/UDCA + isoUDCA) in patients with PBC or PSC. Future studies of bile acid metabolism under UDCA treatment should include measurement of isoUDCA to further elucidate its biological role
AB - The appearance of iso-ursodeoxycholic acid (isoUDCA; 3 beta,7 beta-dihydroxy-5 beta-cholan-24-oic acid) in serum of patients with chronic cholestatic liver disease and of healthy subjects during administration of ursodeoxycholic acid (UDCA) is reported. Comparison of the mass spectrum of the newly appearing bile acid with that of authentic 3 beta,7 beta-dihydroxy-5 beta-cholan-24-oic acid revealed its identity as the 3 beta-epimer of UDCA. The appearance of 13C-isoUDCA in serum after ingestion of 13C-UDCA proved its product precursor relationship with UDCA. The putative intermediate in the epimerization of UDCA to isoUDCA, 3-oxo-7 beta-hydroxy-5 beta-cholan-24-oic acid, was identified in serum of patients with cholestatic liver disease during treatment with UDCA. Serum concentrations of isoUDCA after 4 weeks of UDCA treatment were 1.37 +/- 0.79 mumol/l (mean +/- S.D.) in eight patients with primary biliary cirrhosis (PBC), 1.25 +/- 0.91 mumol/l in six patients with primary sclerosing cholangitis (PSC) and 3.87 +/- 0.44 mumol/l in four healthy controls. The intestinal bacterial flora as well as microsomal enzymes of the liver may be involved in the epimerization of UDCA to isoUDCA as indicated by decreased serum levels of isoUDCA under antibiotic treatment with doxycycline (100 mg/day) in healthy subjects and a correlation (r = 0.873, p less than 0.001) between the hepatic microsomal function measured by the 14C-aminopyrine breath test and the fractional conversion of applied UDCA to isoUDCA (isoUDCA/UDCA + isoUDCA) in patients with PBC or PSC. Future studies of bile acid metabolism under UDCA treatment should include measurement of isoUDCA to further elucidate its biological role
U2 - https://doi.org/10.1016/0168-8278(91)90870-H
DO - https://doi.org/10.1016/0168-8278(91)90870-H
M3 - Article
C2 - 1918882
SN - 0168-8278
VL - 13
SP - 97
EP - 103
JO - Journal of Hepatology
JF - Journal of Hepatology
IS - 1
ER -