Determination of urinary isoursodeoxycholic acid and ursocholic acid in patients during ursodeoxycholic acid treatment
Urinary isoursodeoxycholic acid (isoUDCA) and ursocholic acid (UCA) which are metabolites of ursodeoxycholic acid (UDCA) were analyzed by gas-liquid chromatography in 8 patients with gall stone (GS), 20 with chronic hepatitis (CH) and 13 with compensated liver cirrhosis (LC) during oral administrati...
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| Published in | Kanzo Vol. 39; no. 8; pp. 526 - 532 |
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| Main Authors | , , , , , , , , |
| Format | Journal Article |
| Language | Japanese |
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The Japan Society of Hepatology
1998
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| ISSN | 0451-4203 1881-3593 |
| DOI | 10.2957/kanzo.39.526 |
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| Abstract | Urinary isoursodeoxycholic acid (isoUDCA) and ursocholic acid (UCA) which are metabolites of ursodeoxycholic acid (UDCA) were analyzed by gas-liquid chromatography in 8 patients with gall stone (GS), 20 with chronic hepatitis (CH) and 13 with compensated liver cirrhosis (LC) during oral administration of UDCA 600mg/day. The concentration of total bile acid in fasted urine was 22.48±3.8, 60.94±11.7 and 104.32±28.7 (Mean±SE, μmole/l) in GS, CH and LC, respectively. In patients with GS, the percentage of UDCA in total bile acid was significantly lower, however, the percentages of isoUDCA and UCA were significantly higher than CH and LC patients (UDCA, isoUDCA, UCA: 46.3±6.8, 20.9±5.8, 7.2±3.5 in GS, 64.3±2.6, 10.3±1.7, 4.0±0.9 in CH, 73.3±2.7, 5.1±1.0, 1.9±0.5 (Mean±SE, %) in LC, respectively). Furthermore, the percentage of UDCA in total 7β-hydroxy bile acid significantly increased following liver disease (64.8±9.1, 81.6±2.3 and 92.2±1.3 (Mean±SE, %) in GS, CH and LC, respectively) and was the negative correla ion with serum albumin. Present study suggests that the measurement of UDCA and its metabolites in urine of patient during UDCA administration may be an useful test to evaluate the impairment of hepatic function and enterohepatic circulation. |
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| AbstractList | Urinary isoursodeoxycholic acid (isoUDCA) and ursocholic acid (UCA) which are metabolites of ursodeoxycholic acid (UDCA) were analyzed by gas-liquid chromatography in 8 patients with gall stone (GS), 20 with chronic hepatitis (CH) and 13 with compensated liver cirrhosis (LC) during oral administration of UDCA 600mg/day. The concentration of total bile acid in fasted urine was 22.48±3.8, 60.94±11.7 and 104.32±28.7 (Mean±SE, μmole/l) in GS, CH and LC, respectively. In patients with GS, the percentage of UDCA in total bile acid was significantly lower, however, the percentages of isoUDCA and UCA were significantly higher than CH and LC patients (UDCA, isoUDCA, UCA: 46.3±6.8, 20.9±5.8, 7.2±3.5 in GS, 64.3±2.6, 10.3±1.7, 4.0±0.9 in CH, 73.3±2.7, 5.1±1.0, 1.9±0.5 (Mean±SE, %) in LC, respectively). Furthermore, the percentage of UDCA in total 7β-hydroxy bile acid significantly increased following liver disease (64.8±9.1, 81.6±2.3 and 92.2±1.3 (Mean±SE, %) in GS, CH and LC, respectively) and was the negative correla ion with serum albumin. Present study suggests that the measurement of UDCA and its metabolites in urine of patient during UDCA administration may be an useful test to evaluate the impairment of hepatic function and enterohepatic circulation. |
| Author | AOSHIMA, Masaru NAKAMURA, Kimihide NAKADE, Yukiomi YOKOHAMA, Shiro MAKINO, Isao Aso, Kazunobu SATO, Yoichi YONEDA, Masashi TAKAMOTO, Shujiro |
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| References | 20) Goto J, Miura H, Ando M: A novel enzyme system for the reduction of 3-oxo bile acids in human red blood cells. Steroids 61: 416-420, 1996 7) 中村公英, 秋山建児, 牧野勲: 慢性肝炎患者におけるウルソデオキシコール酸の長期投与効果と血中胆汁酸分画における影響. 日消誌92: 62-71, 1995 11) Marschall HU, Griffiths WJ, Gotze U: The major metabolites of ursodeoxycholic acid in human urine are conjugated with N-acetylglucosamine. Hepatology 20: 845-853, 1994 10) Marschall HU, Materrn H, Wietholtz H: Bile acid N-acetylglucosaminidation: In vivo and in vitro evidence for a selective conjugation reaction of 7β-hydroxylated bile acids in humans. J Clin Invest 89: 1981-1987, 1992 3) Stiehl A, Rudolph G, Raedsch R: Ursodeoxycholic acid-induced changes of plasma and urinary bile acids in patients with primary biliary cirrhosis. Hepatology 12: 492-497, 1990 1) Makino I, Nakagawa S: Changes in biliary lipid and biliary bile acid composition in patients after administration of ursodeoxycholic acid. J Lipd Res 19: 723-728, 1978 4) Poupon RE, Chretien Y, Poupon R: Serum bile acids in primary biliary cirrhosis: Effect of ursodeoxycholic acid therapy. Hepatology 17: 599-604, 1993 26) Lanzini A, Pigozzi G, Facchinetti D: Effect of chronic ursocholic acid administration on bile lipid composition and bile acid pool size in gallstone patients. Scand J Gastroenterol 25: 711-719, 1990 25) Howard PJ, Gleeson D, Murphy GM: Ursocholic acid: bile acid and bile lipid dose response and clinical studies in patients with gall stones. Gut 30: 97-103, 1989 8) Nakamura K, Yoneda M, Kimura A: Increase of sulfated ursodeoxycholic acid in serum and urine of patients with chronic liver disease after ursodeoxycholic acid therapy. J Gastroenterol Hepatol 11: 385-390, 1996 22) Kritchevsky D, Nair PP: Chemistry of the bile acids. In: The bile acids. Vol 1, Edited by Nair PP, Kritchevsky D. Plenum Press, New York, 1971, p1-10 21) Marschall HU, Roeb E, Yildiz Y: Study of human isoursodeoxycholic acid metabolism. J Hepatol 26: 863-870, 1997 5) Nakashima T, Sano A, Seto Y: Unusual trihydroxy bile acids in urine of patients treated with chenodeoxycholate, ursodeoxycholate or rifampicin and those with cirrhosis. Hepatology 11: 255-260, 1990 28) Batta A, Salen G, Abroon J: Ursocholic acid, a hydrophilic bile acid, fails to improve liver function parameters in primary biliary cirrhosis: Comparison with ursodeoxycholic acid. Am J Gastroenterol 92: 1035-1037, 1997 12) Palmer RH: The formation of bile acid sulfates: A new pathway of bile acid metabolism in humans. Proc Natl Acad Sci USA 58: 1047-1050, 1967 19) Floch MH, Katz J, Conn HO: Qualitative and quantitative relationships of the fecal flora in cirrhotic patients with portal systemic encephalopathy and following portacaval anastomosis. Gastroenterology 59: 70-75, 1970 14) Marschall HU, Griffiths WJ, Zhang J: Positions of conjugation of bile acids with glucose and N-acetylglucosamine in vitro. J Lipid Res 35: 1599-1610, 1994 2) Fischer S, Neubrand M, Paumgartner G: Biotransformation of orally administered ursodeoxycholic acid in man as observed in gallbladder bile, serum and urine. Eur J Clin Invest 23: 28-36, 1993 24) Salvioli G, Lugli R, Pradeli JM: Urinary excretion of bile acids during acute administration in man. Eur J Clin Invest 18: 22-28, 1988 15) 南部勝司, 黒田博之, 浪久利彦, 他: Ursodeoxycholic acidによるコレステロール系胆石の溶解機序と血清胆汁酸の定量分析について. 日消誌75: 1768-1780, 1978 27) Tint GS, Batta A, Dayal B: Metabolism of ursocholic acid in humans: Conversion of ursocholic acid to deoxycholic acid. Hepatology 15: 645-650, 1992 17) Maeda M, Ohama H, Takeda H: Identification of 3β, 7β-dihydroxy-5β-cholan-24-oic acid in serum from patients treated with ursodeoxychelic acid. J Lipid Res 25: 14-26, 1984 16) 大浜宏文, 前田稔, 南部勝司: 3β, 7β-dihydroxy-5β-cholan-24-oic acid; ursodeoxycholic acid (UDCA) を投与した胆石患者血清中に見出された新しい胆汁酸. 肝臓21: 238, 1980 18) Beuers U, Fischer S, Spengler U: Formation of iso-ursodeoxycholic acid during administration of ursodeoxycholic acid in man. J Hepatol 13: 97-103, 1991 23) Hansson R, Wikvall K: Hydroxylations in biosynthesis and metabolism of bile acids: Catalytic properties of different forms of cyto- chrome P-450. J Biol Chem 255: 1643-1649, 1980 13) 中村公英: ウルソデオキシコール酸投与患者における尿中硫酸抱合型ウルソデオキシコール酸の定量と硫酸抱合位置の検討. 肝臓11: 814-821, 1994 9) 堀田秀一郎, 中村公英, 牧野勲, 他: ウルソデオキシコール酸投与患者の血中イソウルソデオキシコール酸の測定と臨床的意義. 肝臓36: 283-288, 1995 6) 中村公英, 青島優, 谷光憲, 他: 代償期肝硬変症に対するウルソデオキシコール酸 (UDCA) の治療効果と血中胆汁酸代謝に及ぼす影響. 日消誌89: 2762-2770, 1992 |
| References_xml | – reference: 5) Nakashima T, Sano A, Seto Y: Unusual trihydroxy bile acids in urine of patients treated with chenodeoxycholate, ursodeoxycholate or rifampicin and those with cirrhosis. Hepatology 11: 255-260, 1990 – reference: 11) Marschall HU, Griffiths WJ, Gotze U: The major metabolites of ursodeoxycholic acid in human urine are conjugated with N-acetylglucosamine. Hepatology 20: 845-853, 1994 – reference: 1) Makino I, Nakagawa S: Changes in biliary lipid and biliary bile acid composition in patients after administration of ursodeoxycholic acid. J Lipd Res 19: 723-728, 1978 – reference: 18) Beuers U, Fischer S, Spengler U: Formation of iso-ursodeoxycholic acid during administration of ursodeoxycholic acid in man. J Hepatol 13: 97-103, 1991 – reference: 3) Stiehl A, Rudolph G, Raedsch R: Ursodeoxycholic acid-induced changes of plasma and urinary bile acids in patients with primary biliary cirrhosis. Hepatology 12: 492-497, 1990 – reference: 6) 中村公英, 青島優, 谷光憲, 他: 代償期肝硬変症に対するウルソデオキシコール酸 (UDCA) の治療効果と血中胆汁酸代謝に及ぼす影響. 日消誌89: 2762-2770, 1992 – reference: 7) 中村公英, 秋山建児, 牧野勲: 慢性肝炎患者におけるウルソデオキシコール酸の長期投与効果と血中胆汁酸分画における影響. 日消誌92: 62-71, 1995 – reference: 17) Maeda M, Ohama H, Takeda H: Identification of 3β, 7β-dihydroxy-5β-cholan-24-oic acid in serum from patients treated with ursodeoxychelic acid. J Lipid Res 25: 14-26, 1984 – reference: 12) Palmer RH: The formation of bile acid sulfates: A new pathway of bile acid metabolism in humans. Proc Natl Acad Sci USA 58: 1047-1050, 1967 – reference: 4) Poupon RE, Chretien Y, Poupon R: Serum bile acids in primary biliary cirrhosis: Effect of ursodeoxycholic acid therapy. Hepatology 17: 599-604, 1993 – reference: 13) 中村公英: ウルソデオキシコール酸投与患者における尿中硫酸抱合型ウルソデオキシコール酸の定量と硫酸抱合位置の検討. 肝臓11: 814-821, 1994 – reference: 24) Salvioli G, Lugli R, Pradeli JM: Urinary excretion of bile acids during acute administration in man. Eur J Clin Invest 18: 22-28, 1988 – reference: 8) Nakamura K, Yoneda M, Kimura A: Increase of sulfated ursodeoxycholic acid in serum and urine of patients with chronic liver disease after ursodeoxycholic acid therapy. J Gastroenterol Hepatol 11: 385-390, 1996 – reference: 26) Lanzini A, Pigozzi G, Facchinetti D: Effect of chronic ursocholic acid administration on bile lipid composition and bile acid pool size in gallstone patients. Scand J Gastroenterol 25: 711-719, 1990 – reference: 23) Hansson R, Wikvall K: Hydroxylations in biosynthesis and metabolism of bile acids: Catalytic properties of different forms of cyto- chrome P-450. J Biol Chem 255: 1643-1649, 1980 – reference: 19) Floch MH, Katz J, Conn HO: Qualitative and quantitative relationships of the fecal flora in cirrhotic patients with portal systemic encephalopathy and following portacaval anastomosis. Gastroenterology 59: 70-75, 1970 – reference: 20) Goto J, Miura H, Ando M: A novel enzyme system for the reduction of 3-oxo bile acids in human red blood cells. Steroids 61: 416-420, 1996 – reference: 28) Batta A, Salen G, Abroon J: Ursocholic acid, a hydrophilic bile acid, fails to improve liver function parameters in primary biliary cirrhosis: Comparison with ursodeoxycholic acid. Am J Gastroenterol 92: 1035-1037, 1997 – reference: 10) Marschall HU, Materrn H, Wietholtz H: Bile acid N-acetylglucosaminidation: In vivo and in vitro evidence for a selective conjugation reaction of 7β-hydroxylated bile acids in humans. J Clin Invest 89: 1981-1987, 1992 – reference: 25) Howard PJ, Gleeson D, Murphy GM: Ursocholic acid: bile acid and bile lipid dose response and clinical studies in patients with gall stones. Gut 30: 97-103, 1989 – reference: 27) Tint GS, Batta A, Dayal B: Metabolism of ursocholic acid in humans: Conversion of ursocholic acid to deoxycholic acid. Hepatology 15: 645-650, 1992 – reference: 9) 堀田秀一郎, 中村公英, 牧野勲, 他: ウルソデオキシコール酸投与患者の血中イソウルソデオキシコール酸の測定と臨床的意義. 肝臓36: 283-288, 1995 – reference: 21) Marschall HU, Roeb E, Yildiz Y: Study of human isoursodeoxycholic acid metabolism. J Hepatol 26: 863-870, 1997 – reference: 22) Kritchevsky D, Nair PP: Chemistry of the bile acids. In: The bile acids. Vol 1, Edited by Nair PP, Kritchevsky D. Plenum Press, New York, 1971, p1-10 – reference: 2) Fischer S, Neubrand M, Paumgartner G: Biotransformation of orally administered ursodeoxycholic acid in man as observed in gallbladder bile, serum and urine. Eur J Clin Invest 23: 28-36, 1993 – reference: 15) 南部勝司, 黒田博之, 浪久利彦, 他: Ursodeoxycholic acidによるコレステロール系胆石の溶解機序と血清胆汁酸の定量分析について. 日消誌75: 1768-1780, 1978 – reference: 16) 大浜宏文, 前田稔, 南部勝司: 3β, 7β-dihydroxy-5β-cholan-24-oic acid; ursodeoxycholic acid (UDCA) を投与した胆石患者血清中に見出された新しい胆汁酸. 肝臓21: 238, 1980 – reference: 14) Marschall HU, Griffiths WJ, Zhang J: Positions of conjugation of bile acids with glucose and N-acetylglucosamine in vitro. J Lipid Res 35: 1599-1610, 1994 |
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| Title | Determination of urinary isoursodeoxycholic acid and ursocholic acid in patients during ursodeoxycholic acid treatment |
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