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标题：Isoursodeoxycholic acid: metabolism and therapeutic effects in primary biliary cirrhosis
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作者：Hanns-Ulrich Marschall ; Ulrika Broomé ; Curt Einarsson 等
期刊名称：JLR Papers In Press
印刷版ISSN：0022-2275
电子版ISSN：1539-7262
出版年度：2001
卷号：42
期号：5
页码：735-742
语种：English
出版社：American Society for Biochemistry and Molecular Biology
摘要：Significant amounts of ursodeoxycholic acid (UDCA) used for the treatment of patients with primary biliary cirrhosis (PBC) become epimerized at C-3 to isoUDCA. We investigated the metabolism of isoUDCA and a possible pharmacologic effect in five patients (51.4 ± 5.8 years old; 3 females, 2 males) with PBC and persistent elevations of γ-glutamyl transpeptidase (γ-GT) and alkaline phosphatase despite treatment with UDCA for more than one year. Serum samples were analyzed for bile acid metabolites and surrogate markers of cholestasis in 4-week intervals after 1 g/d UDCA, wash-out, 0.5 g/d isoUDCA, 0.75 g/d isoUDCA, 0.75 g/d UDCA, and two further periods with 1 g/d UDCA. Bile acids in urine were analyzed after wash-out, 0.5 and 0.75 g/d isoUDCA, and 0.75 and 1 g/d UDCA. During wash-out, AST, AP, and γ-GT rose significantly ( P N -acetylglucosamine, indicating hepatic formation and systemic secretion of glycosidic conjugates. In PBC patients, isoUDCA becomes isomerized to UDCA and has similar effects on surrogate markers of cholestasis. Thus, isoUDCA has pro-drug characteristics. —Marschall, H-U., U. Broomé, C. Einarsson, G. Alvelius, H. G. Thomas, and S. Matern. Isoursodeoxycholic acid: metabolism and therapeutic effects in primary biliary cirrhosis. J. Lipid Res. 2001. 42: 735–742.
关键词：ursodeoxycholic acid ; bile acid metabolis ; N -acetylglucosaminidation ; glucosidation ; glucuronidation ; gas chromatography-mass spectrometry ; electrospray mass spectrometry