Clinical pharmacokinetics of therapeutic bile acids

Clinical Pharmacokinetics

Volumn 30, Issue 5, 1996, Pages 333-358

  Crosignani, Andrea ^a   Setchell, Kenneth D R ^b   Invernizzi, Pietro ^a   Larghi, Alberto ^a   Rodrigues, Cecilia M P ^b   Podda, Mauro ^a  

^a UNIVERSITY OF MILAN   (Italy)

^b CINCINNATI CHILDREN'S HOSPITAL MEDICAL CENTER   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

BILE ACID; CHENODEOXYCHOLIC ACID; CHOLIC ACID; DEOXYCHOLIC ACID; GLUCOSE; GLYCEROL; LITHOCHOLIC ACID; N ACETYLGLUCOSAMINE; SERUM ALBUMIN; TAURINE; URSODEOXYCHOLIC ACID;

BILE ACID METABOLISM; BILE SECRETION; BIOTRANSFORMATION; CHOLESTATIC HEPATITIS; CHRONIC HEPATITIS; CHRONIC LIVER DISEASE; CYSTIC FIBROSIS; DOSE LIVER FUNCTION RELATION; DRUG ABSORPTION; DRUG CONJUGATION; ENTEROHEPATIC CIRCULATION; HUMAN; INTESTINE ABSORPTION; LIVER CIRRHOSIS; LIVER FUNCTION; ORAL DRUG ADMINISTRATION; PHARMACODYNAMICS; PRIMARY BILIARY CIRRHOSIS; PRIMARY SCLEROSING CHOLANGITIS; PRIORITY JOURNAL; REVIEW;

EID: 0029922694     PISSN: 03125963     EISSN: None     Source Type: Journal    
DOI: 10.2165/00003088-199630050-00002     Document Type: Review

References (156)

1. Danzinger RG, Hofmann AF, Schoenfield LJ, et al. Dissolution of cholesterol gallstones by chenodeoxycholic acid. N Engl J Med 1972; 286: 1-8
2. Makino I, Shinozaki K, Yoshino K, et al. Dissolution of cholesterol gallstones by ursodeoxycholic acid. Jpn J Gastroenterol 1975; 72: 690-702
3. Rubin RA, Kowalski TE, Khandelwal M, et al. Ursodiol for hepatobiliary disorders. Ann Intern Med 1994; 121: 207-18
4. Podda M, Zuin M, Batterzati PM, et al. Efficacy and safety of a combination of chenodeoxycholic acid and ursodeoxycholic acid for gallstone dissolution: a comparison with ursodeoxycholic acid alone. Gastroenterology 1989; 96: 222-9
5. Salen G, Berginer V, Shore V, et al. Increased concentration of cholestanol and apolipoprotein B in the cerebrospinal fluid of patients with cerebrotendinous xanthomatosis. Effect of chenodeoxycholic acid. N Engl J Med 1987; 316: 1233-8
6. Setchell KDR, Balistreri WF, Piccoli DA, et al. Oral bile acid therapy in the treatment of inborn errors in bile acid synthesis associated with liver disease. In: Paumgartner G, Stiehl A, Gerok W, editors. Bile acids as therapeutic agents. Lancaster: MTP Press, 1990: 367-73
7. Leuschner U, Leuschner M, Sieratzki J, et al. Gallstone dissolution with ursodeoxycholic acid in patients with chronic active hepatitis and two years follow-up: a pilot study. Dig Dis Sci 1985; 30: 642-9
8. Poupon RE, Poupon R, Balkau B and the UDCA-PBC Study Group. Ursodiol for long-term treatment of primary biliary cirrhosis. N Engl J Med 1994; 330: 1342-7
9. Hofmann AF, Popper H. Ursodeoxycholic acid for primary biliary cirrhosis. Lancet 1987; II: 398-9
10. Guldutuna S, Zimmer G, Imhof M, et al. Molecular aspects of membrane stabilization by ursodeoxycholate. Gastroenterology 1993; 104: 1736-44
11. 2+ signals in isolated rat hepatocytes. Gastroenterology 1993; 104: 604-12
12. Bouscarel B, Gettys TW, Fromm H, et al. Ursodeoxycholic acid inhibits glucagon-induced cAMP formation in hamster hepatocytes: a role for PKC. Am J Physiol 1995; 268: G300-10
13. Invernizzi P, Salzman AL, Setchell KDR. Ursodeoxycholic acid inhibits induction of the human intestinal epithelial nitric oxide synthase [abstract]. Hepatology 1995; 22: 361A
14. Krahenbuhl S, Fischer S, Talos C, et al. Ursodeoxycholate protects oxidative mitochondrial metabolism from bile acid toxicity: dose-response study in isolated rat liver mitochondria. Hepatology 1994; 20: 1595-60
15. Yoshikaws M, Tsujii T, Matsumura K, et al. Immunomodulatory effects of ursodeoxycholic acid on immune responses. Hepatology 1992; 16: 358-64
16. Bachrach WH, Hofmann AF. Ursodeoxycholic acid in the treatment of cholesterol cholelithiasis. Part I. Dig Dis Sci 1982; 27: 737-61
17. Bachrach WH, Hofmann AF. Ursodeoxycholic acid in the treatment of cholesterol cholelithiasis. Part II. Dig Dis Sci 1982; 27: 833-56
18. Ward A, Brodgen RN, Heel RC, et al. Ursodeoxycholic acid: a review of its pharmacological properties and therapeutic efficacy. Drugs 1984; 27: 95-131
19. de Caestecker JS, Jazrawi RP, Petroni ML, et al. Ursodeoxycholic acid in liver disease. Gut 1991; 32: 1061-5
20. Queneau PE, Montet JC. Hepatoprotection by hydrophilic bile salts. J Hepatol 1994; 21: 260-8
21. Hofmann AF. Pharmacology of ursodeoxycholic acid, an enterohepatic drug. Scand J Gastroenterol 1994; 29 Suppl. 204: 1-15
22. Simoni P, Cerrè C, Cipolla A, et al. Bioavailability study of a new, sinking, enteric-coated ursodeoxycholic acid formulation. Pharmacol Res 1995; 31: 1-5
23. Hofmann AF, Roda A. Physicochemical properties of bile acids and their relationship to biological properties: an overview of the problem. J Lipid Res 1984; 25: 1477-88
24. Hofmann AF. Chemistry and enterohepatic circulation of bile acids. Hepatology 1984; 4: 4S-14S
25. Ota M, Minami Y, Hoshita T. Intestinal absorption of ursodeoxycholic, glycoursodeoxycholic and tauroursodeoxycholic acids in rats. J Pharmacobiodyn 1985; 8: 114-8
26. Walker S, Stiehl A, Raedsch R, et al. Absorption of urso- and chenodeoxycholic acid and their taurine and glycine conjugates in rat jejunum, ileum, and colon. Digestion 1985; 32: 47-52
27. van Berge Henegouwen GP, Hofmann AF, Gaginella TS. Pharmacology of chenodeoxycholic acid. I. Pharmaceutical properties. Gastroenterology 1977; 73: 291-9
28. Igimi H, Carey MC. Ph-solubility relations of chenodeoxycholic and ursodeoxycholic acids: physical-chemical basis for dissimilar solution and membrane phenomena. J Lipid Res 1980; 21: 72-89
29. van Berge Henegouwen GP, Hofmann AF. Pharmacology of chenodeoxycholic acid. II. Absorption and metabolism. Gastroenterology 1977; 73: 300-9
30. Hofmann AF. Pharmacology of chenodeoxycholic and ursodeoxycholic acids in man. In: Paumgartner G, Stiehl A, Gerok W, editors. Bile acids and cholesterol in health and disease. Boston: MTP Press Limited, 1983: 301-36
31. LaRusso NF, Thistle JL. Ursodeoxycholic acid ingestion after ileal resection: effect on biliary bile acid and lipid composition. Dig Dis Sci 1981; 26: 705-9
32. Shinozaki K. Pharmacokinetic study of oral ursodeoxycholic acid tolerance test. Acta Hepatol Jpn 1979; 20: 782-94
33. Tashiro A. Oral ursodeoxycholic acid tolerance test for patients with hepatobiliary disease. Acta Hepatol Jpn 1979; 20: 369-75
34. Kubota K, Yamaoka K, Ishizaki T, et al. A pharmacokinetic analysis of enterohepatic circulation of ursodeoxycholic acid, a drug with a high hepatic extraction but a small clearance. Res Comm Chem Pathol Pharmacol 1988; 62: 309-26
35. Stiehl A, Raedsch R, Rudolph G. Heal excretion of bile acids: Comparison with biliary bile composition and effect of ursodeoxycholic acid treatment. Gastroenterology 1988; 94: 1201-6
36. Stiehl A, Raedsch R, Rudolph G. Acute effects of ursodeoxycholic and chenodeoxycholic acid on the small intestinal absorption of bile acids. Gastroenterology 1990; 98: 424-8
37. Walker S, Rudolph G, Raedsch R, et al. Intestinal absorption of ursodeoxycholic acid in patients with extrahepatic biliary obstruction and bile drainage. Gastroenterology 1992; 102: 810-5
38. + on bile acid uptake by isolated rat hepatocytes. Hoppe Seyler's Z Physiol Chem 1978; 359: 181-92
39. Duffy MC, Blitzer BL, Boyer JL. Direct determination of the driving force for taurocholate uptake into the rat liver plasma membrane vesicles. J Clin Invest 1983; 72: 1470-81
40. van Dyke RW, Stephens JE, Scharschmidt BF. Bile acid transport in cultured hepatocytes. Am J Physiol 1980; 239: G439-44
41. Inoue M, Kinne R, Tran T, et al. Taurocholate transport by rat liver sinusoidal membrane vesicles: evidence for sodium cotransport. Hepatology 1982; 2: 572-9
42. Schwartz LR, Burr R, Schwenk M, et al. Uptake of taurocholic acid into isolated rat liver cells. Eur J Biochem 1975; 55: 617-23
43. Aldini R, Roda A, Simoni P, et al. Uptake of bile acids by perfused rat liver: evidence of a structure-activity relationship. Hepatology 1989; 10: 840-5
44. Poupon R, Chretien Y, Parquet M, et al. Hepatic transport of bile acids in the isolated perfused rat liver. Structure-kinetic relationship. Biochem Pharmacol 1988; 37: 209-12
45. Zouboulis-Vafiadis I, Dumont M, Erlinger S. Conjugation is rate limiting in hepatic transport of ursodeoxycholate in the rat. Am J Physiol 1982; 243: G208-13
46. Roda A, Cappelleri G, Aldini R, et al. Quantitative aspects of interaction of bile acids with human serum albumin. J Lipid Res 1982; 23: 490-5
47. Koopman BJ, Kuipers F, Bijleveld CMA, et al. Determination of cholic acid and chenodeoxycholic acid pool sizes and fractional turnover rates by means of stable isotope dilution technique, making use of deuterated cholic acid and chenodeoxycholic acid. Clin Chim Acta 1988; 175: 143-56
48. Hoshita T, Kono M, Matsumoto M, et al. Metabolism of bile acids. I. Absorption, distribution, excretion and metabolism of ursodeoxycholic acid. Yakugaku Zasshi 1974; 94: 1196-205
49. Ota M, Isobe J, Tsuji Y, et al. Metabolism of bile acids IV. Absorption, distribution, excretion and metabolism of orally administered ursodeoxycholic acid in rats. Hiroshima J Med Sci 1977; 26: 233-51
50. Ota M, Tsuji Y, Hoshita T. Metabolism of bile acids VII. Metabolism of ursodeoxycholic acid in female rats. Hiroshima J Med Sci 1978; 27: 139-45
51. Fedorowski T, Salen G, Colalillo A, et al. Metabolism of ursodeoxycholic acid in man. Gastroenterology 1977; 73: 1131-7
52. Schersten T. Bile acid conjugation. In: Fishman O, editor. Metabolic conjugation and metabolic hydrolysis. Vol. 2. New York: Academic Press, 1971: 75-121
53. Batta AK, Salen G, Shefer S, et al. The effect of tauroursodeoxycholic acid and taurine supplementation on biliary bile acid composition. Hepatology 1982; 2: 811-6
54. Sjovall J. Dietary glycine and taurine on bile acid conjugation in man. Bile acids and steroids 75. Proc Soc Exp Biol Med 1959; 100: 676-8
55. Cowen AE, Korman MG, Hofmann AF, et al. Metabolism of lithocholate in healthy man. I. Biotransformation and biliary excretion of intravenously administered lithocholate, lithocholylglycine, and their sulfates. Gastroenterology 1975; 69: 59-66
56. 22-ursodeoxycholic acid, a unique metabolite of administered ursodeoxycholic acid in rats, indicating partial β-oxidation as a major metabolic pathway for bile acid metabolism. Biochemistry 1995; 34: 4169-78
57. 14C in rat. J Biol Chem 1964; 239: 102-5
58. 22-bile acids in rats is not gender specific and occurs in the peroxisome. J Lipid Res. In press
59. Marschall HU, Matern H, Wietholtz H, et al. 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 1992; 89: 1981-7
60. Setchell KDR, Balistreri W, Lin Q, et al. Metabolism of ursodeoxycholic acid in normal subjects and in patients with choleslatic liver disease: biotrasformation by conjugation and urinary excretion. In: Paumgartner G, Stiehl A, Gerok W, editors. Bile Acids and the Hepatobiliary Sistem. Lancaster: MTP Press, 1993: 245-9
61. Dowling RH, Mack E, Small DM. Effects of controlled interruption of the enterohepatic circulation of bile salts by biliary diversion and by ileal resection on bile salt secretion, synthesis and pool-size in the rhesus monkey. J Clin Invest 1970; 79: 82-9
62. Northfield TC, Hofmann AF. Biliary lipid output during three meals and an overnight fast. I. Relationship to bile acid pool-size and cholesterol saturation of bile in gallstone and control subjects. Gut 1975; 16: 1-11
63. Rodrigues CMP, Kren BT, Steer CJ, Setchell KDR. Tauroursodeoxycholic acid is more effective than ursodeoxycholic acid in increasing liver ursodeoxycholate concentrations and reducing lithocholate formation in rats. Gastroenterology 1995; 109: 564-72
64. Northfield TC, McColl I. Postprandial concentrations of free and conjugated bile acids down the length of the normal human small intestine. Gut 1973; 14: 513-8
65. Setchell KDR, O'Connell N, Cummings J. Intraluminal bile acid composition along the entire length of the human intestine [abstract]. FASEB J 1993 Feb 23; 7 (4): A722
66. Batta AK, Salen G, Arora R, et al. Side-chain conjugation prevents bacterial 7-dehydroxylation of bile acids. J Biol Chem 1990; 265: 10925-8
67. Setchell KDR, Rodrigues CMP, Podda M, et al. Metabolism of tauroursodeoxycholic acid orally administered in patients with primary biliary cirrhosis. Gut 1996; 38: 439-46
68. Fedorowski T, Salen CJ, Tint GS, et al. Transformation of chenodeoxycholic acid and ursodeoxycholic acid by human intestinal bacteria. Gastroenterology 1979; 77: 1068-73
69. Higashi H, Setoguchi T, Katsuki T. Interconversion between chenodeoxycholic and ursodeoxycholic in anaerobic cultures of intestinal bacteria and reduction of 7-ketolithocholic acid to both bile acids. Acta Hepatol Jpn 1978; 19: 803
70. Aries V, Hill MJ. Degradation of steroids by intestinal bacteria. II. Enzymes catalyzing the oxidoreduction of 3α, 7α, and 12α-hydroxyl groups in cholic acid, and the dehydroxylation of the 7-hydroxyl group. Biochem Biophys Acta 1970; 202: 535-43
71. Fromm H, Carlson GL, Hofmann AF, et al. Metabolism in man of 7-ketolithocholic acid: precursor of cheno- and ursodeoxycholic acids. Am J Physiol 1980; 239: G161-6
72. 6-lithocholenic acid in humans. Am J Physiol 1993; 264: G163-71
73. Kihira K, Yamauchi T, Kuramoto T, et al. Comparative studies of metabolism of simultaneously administered chenodeoxycholic acid and ursodeoxycholic acid in hamsters. Steroids 1994; 59: 431-5
74. Javitt NB. Ursodeoxycholic acid therapy: the baby and the bathwater [editorial]. Hosp Pract 1992; 27: 15-6
75. Crosignani A, Battezzati PM, Camisasca M, et al. Tauroursodeoxycholic acid for treatment of primary biliary cirrhosis: a dose-response study [abstract]. Hepatology 1993; 18: 176A
76. Crosignani A, Battezzati PM, Setchell KDR, et al. Tauroursodeoxycholic acid for the treatment of primary biliary cirrhosis: a dose-response study. Dig Dis Sci. In press
77. Setchell KDR, Rodigues CMP, Podda M, et al. Tauroursodeoxycholic acid (TUDCA) appears more effective than UDCA at displacing hydrophobic bile acids from the bile acid pool of patients with primary biliary cirrhosis (PBC) [abstract]. Hepatology 1994; 20: 150A
78. Albini E, Beliuco G, Marca G. In vitro transformation of chenodeoxycholic acid and ursodeoxycholic acid by human fecal flora. Acta Ther 1980; 6: 339-51
79. Ota M, Matsumoto N, Kuramoto T, et al. Metabolism of bile acids V. Metabolism of ursodeoxycholic acid in rhesus monkey. Hiroshima J Med Sci 1977; 26: 253-62
80. Almé B, Bremmelgaard A, Sjövall J, et al. Analysis of metabolic profiles of bile acids in urine using a lipophilic anion exchanger and computerized gas-liquid chromatography-rnass spectrometry. J Lipid Res 1977; 18: 339-62
81. Hofmann AF, Cummings SA. Measurement of bile acid and cholesterol kinetics in man by isotope dilution: principles and applications. In: Barbara L, Dowling RH, Hofmann AF, et al., editors. Bile acids in gastroenterology. Lancaster: MTP Press Limited, 1983: 75-117
82. Nilsell K, Angelin B, Einarsson K. Comparative effect of ursodeoxycholic acid and chenodeoxycholic acid on bile acid kinetics and biliary lipid secretion. Gastroenterology 1983; 85: 1248-56
83. Roda E, Roda A, Sama C, et al. Effect of ursodeoxycholic acid administration on biliary lipid composition and bile kinetics in cholesterol gallstone patients. Dig Dis Sci 1979; 24: 123-8
84. Tint GS, Salen G, Shefer S. Effect of ursodeoxycholic acid and chenodeoxycholic acid on cholesterol and bile acid metabolism. Gastroenterology 1986; 91: 1007-18
85. Heuman DM, Vlahcevic ZR, Bailey ML, et al. Regulation of bile acid synthesis. II. Effect of bile acid feeding on enzymes regulating hepatic cholesterol and bile acid synthesis in the rat. Hepatology 1988; 8: 892-7
86. Kitani K, Kanai S. Effect of ursodeoxycholate on the bile flow in the rat. Life Sci 1982; 31: 1973-85
87. Kanai S, Kitani K, Sato Y. Difference in the effects of ursodeoxycholate and its taurine conjugate on the biliary excretion of sulfobromophthalein in the rat. J Hepatol 1990; 10: 174-9
88. Kanai S, Kitani K, Sato Y. Bile secretory characteristics of β-muricholate and its taurine conjugate are similar to those of ursodeoxycholate in the rat. Life Sci 1991; 48: 948-57
89. Kitani K, Kanai S, Sato Y, et al. Tauro α-muricholate is as effective as tauro β-muricholate and tauroursodeoxycholate in preventing taurochenodeoxycholate-induced liver damage in the rat. Hepatology 1994; 19: 1007-12
90. Gurantz D, Hofmann AF. Influence of bile acid structure on bile flow and biliary lipid secretion in the hamster. Am J Physiol 1984; 247: G736-48
91. Grundy SM, Metzger AL. A physiologic method for estimation of hepatic secretion of biliary lipids in man. Gastroenterology 1972; 62: 1200-17
92. Leiss O, von Bergmann K. Effects of bile acid feeding on lipoprotein concentration, change in cholesterol synthesis and biliary lipid secretion in patients with radiolucent gallstones. In: Paumgartner G, Stiehl A, Gerok W, editors. Bile acids and lipids. Lancaster: MTP Press, 1981: 247-53
93. Roda E, Mazzella G, Roda A, et al. Effect of chenodeoxycholic acid and ursodeoxycholic acid administration on biliary lipid secretion in normal weight and obese gallstone patients. In: Paumgartner G, Stiehl A, Gerok W, editors. Bile acids and lipids. Lancaster: MTP Press, 1981: 189-93
94. Key PH, Bonorris GG, Marks JV, et al. Biliary lipid synthesis and secretion in gallstone patients before and during treatment with CDCA. J Lab Clin Med 1980; 95: 816-26
95. Northfield TC, LaRusso NF, Hofmann AF, et al. Biliary lipid output during three meals and an overnight fast. II. Effect of chenodeoxycholic acid treatment in gallstone subjects. Gut 1975; 16: 12-7
96. von Bergmann K, Gutsfeld M, Schulze-Hagen K, et al. Effects of ursodeoxycholic acid on biliary lipid secretion in patients with radiolucent gallstones. In: Paumgartner G, Stiehl A, Gerok W, editors. Biological effects of bile acids. Lancaster: MTP Press, 1979: 61-6
97. Danzinger RG, Hofmann AF, Schoenfield LJ, et al. Effect of oral chenodeoxycholic acid on bile acid kinetics and biliary lipid composition in women with cholelithiasis. J Clin Invest 1973; 52: 2809-21
98. Vonk RJ, Kneepkens CMF, Havinga R, et al. Enterohepatic circulation in man: a simple method for the determination of duodenal bile acids. J Lipid Res 1986; 27: 901-4
99. Carulli N, Ponz de Leon M, Zironi F, et al. Hepatic cholesterol and bile acid metabolism in subjects with gallstones: comparative effects of short-term feeding of chenodeoxycholic and ursodeoxycholic acid. J Lipid Res 1980; 21: 35-43
100. Salen G, Colalillo A, Verga D, et al. The effect of high and low doses of ursodeoxycholic acid on gallstone dissolution in humans. Gastroenterology 1980; 78: 1412-8
101. Schoenfield LJ, Lachin JM, the NCGS Steering Committee, and the NCOS Group. National Cooperative Gallstone Study: a controlled trial of the efficacy and safety of chenodeoxycholic acid for dissolution of gallstone. Ann Intern Med 1981; 95: 257-82
102. Matoba N, Une M, Hoshita T. Identification of unconjugated bile acids in human bile. J Lipid Res 1986; 27: 1154-62
103. Setchell KDR, Matsui A. Serum bile acid analysis. Clin Chim Acta 1983; 127: 1-17
104. Makino I, Nakagawa S, Mashino K. Conjugated and unconjugated serum bile acid levels in patients with hepatobiliary diseases. Gastroenterology 1969; 56: 1033-9
105. Setchell KDR, Lawson AM, Blackstock EJ, et al. Diurnal changes in serum unconjugated bile acids in normal man. Gut 1982; 23: 637-42
106. Setchell KDR, Street JM, Sjovall J. Fecal bile acids. In: Setchell KDR, Kritchevsky D, Nair PP, editors. The bile acids. Vol. 4. Methods and applications. New York: Plenum Press, 1988; 441-570
107. Makino I, Nakagawa S. Changes in biliary lipid and biliary bile acid composition in patients after administration of ursodeoxycholic acid. J Lipid Res 1979; 19: 723-8
108. Salvioli G, Salati R, Fratalocchi A, et al. Ursodeoxycholic acid therapy for radiolucent gallstone dissolution. Curr Ther Res 1979; 26: 995-1004
109. Thistle JL, LaRusso NF, Hofmann AF, et al. Differing effects of ursodeoxycholic or chenodeoxycholic acid on biliary cholesterol saturation and bile acid metabolism in man: a dose-response study. Dig Dis Sci 1982; 27: 161-8
110. Batta AK, Salen G, Shefer S, et al. Effect of ursodeoxycholic acid on bile acid metabolism in primary biliary cirrhosis. Hepatology 1989; 10: 414-9
111. Batta AK, Arora R, Salen G, et al. Characterization of serum and urinary bile acids in patients with primary biliary cirrhosis by gas-liquid chromatography-mass spectrometry: effect of ursodeoxycholic acid treatment. J Lipid Res 1989; 30: 1953-62
112. Chretien Y, Poupon R, Gherardt MF, et al. Bile acid glycine and taurine conjugates in serum of patients with primary biliary cirrhosis: effect of ursodeoxycholic acid treatment. Gut 1989; 30: 1110-5
113. Stiehl A, Rudolph G, Raedsch R, et al. Ursodeoxycholic acid-induced changes of plasma and urinary bile acids in patients with primary biliary cirrhosis. Hepatology 1990; 12: 492-7
114. Crosignani A, Podda M, Battezzati PM, et al. Changes in bile acid composition in patients with primary biliary cirrhosis induced by ursodeoxycholic acid administration. Hepatology 1991; 14: 1000-7
115. Poupon RE, Chretien Y, Poupon R, et al. Serum bile acids in primary biliary cirrhosis: Effect of ursodeoxycholic acid therapy. Hepatology 1993; 17: 599-604
116. Batta AK, Salen G, Mirchandani R, et al. Effect of long-term treatment with ursodiol on clinical and biochemical features and biliary bile acid metabolism in patients with primary biliary cirrhosis. Am J Gastroentlerol 1993; 88: 691-700
117. Poupon R, Poupon RE, Lebrec D, et al. Mechanisms for reduced hepatic clearance and elevated plasma levels of bile acids in cirrhosis. Gastroenterology 1981; 80: 1438-44
118. Sauer P, Kloters-Plachky P, Stiehl A. Effects of cholestasis on intestinal absorption of bile acids in rat [abstract]. Hepatology 1994; 20: 396A
119. Jazrawi RP, de Caestecker JS, Goggin PM, et al. Kinetics of hepatic bile acid handling in cholestatic liver disease: effect of ursodeoxycholic acid. Gastroenterology 1994; 106: 134-42
120. Back P. Identification and quantitative determination of urinary bile acids excreted in cholestasis. Clin Chim Acta 1973; 44: 199-207
121. Stiehl A, Becker M, Czygan P, et al. Bile acids and their sulphaled and glucuronidated derivatives in bile, plasma, and urine of children with intrahepatic cholestasis: effects of phenobarbital treatment. Eur J Clin Invest 1980; 10: 307-16
122. Stiehl A, Raedsch R, Rudolph G, et al. Biliary and urinary excretion of sulfated, glucuronidated and tetrahydroxylated bile acids in cirrhotic patients. Hepatology 1985; 5: 492-5
123. Bartholomew TC, Summerfield A, Billing BH, et al. Bile acid profiles of human serum and skin intestinal fluid and their relationship to pruritus studied by gas chromatography-mass spectrometry. Clin Sci 1982; 63: 65-73
124. Kesaniemi YA, Salaspuro MP, Vuoristo M, et al. Biliary lipid secretion in chronic cholestatic liver disease. Gut 1982; 23: 931-8
125. Roda E, Mazzella G, Villanova M, et al. Effects of ursodeoxycholic acid administration on biliary lipid secretion in primary biliary cirrhosis. Dig Dis Sci 1989; 34: 52S-8S
126. Roda E, Bazzoli F, Mazzella G, et al. Effect of age and sex on bile acid metabolism and biliary lipid secretion in normal subjects and gallstone patients. In: Paumgartner G, Stiehl A, Gerok W, editors. Bile acids and the liver. Lancaster: MTP Press, 1987: 225-7
127. Mazzella G, Parini P, Bazzoli F, et al. Ursodeoxycholic acid administration on bile acid metabolism in patients with early stages of primary biliary cirrhosis. Dig Dis Sci 1993; 38: 896-902
128. Lindstedt S. Turnover of cholic acid in man. Acta Physiol Scand 1957; 40: 1-9
129. Beuers U, Spengler U, Zwiebel FM, et al. Effect of ursodeoxycholic acid on the kinetics of the major hydrophobic bile acids in health and in chronic cholestatic liver disease. Hepatology 1992; 15: 603-8
130. Rudolph G, Endele R, Senn M, et al. Effect of ursodeoxycholic acid on the kinetics of cholic acid and chenodeoxycholic acid in patients with primary sclerosing cholangitis. Hepatology 1993; 17: 1028-32
131. Makino I, Hashimoto H, Shinozaki K, et al. Sulfated and nonsulfated bile acids in urine, serum, and bile of patients with hepatobiliary diseases. Gastroenterology 1975; 68: 545-53
132. Podda M, Ghezzi C, Battezzati PM, et al. Effect of different doses of ursodeoxycholic acid in chronic liver disease. Dig Dis Sci 1989; 34: 59S-65S
133. Podda M, Ghezzi C, Battezzati PM, et al. Ursodeoxycholic acid in chronic liver disease. J Clin Gastroenterol 1988; 10: S25-31
134. Podda M, Ghezzi C, Battezzati PM, et al. Effects of Ursodeoxycholic acid (UDCA) on liver function tests and bile acid metabolism in anicteric primary biliary cirrhosis (PBC): a dose-response study [abstract]. Hepatology 1988; 8: 1266A
135. Rodrigues CMP, Kren BT, Steer CJ, et al. The site-specific delivery of ursodeoxycholic acid to the rat colon by sulfate conjugation. Gastroenterology 1995; 109: 1835-44
136. van Berge Henegouwen GP, Brandt KH, Eyssen H, et al. Sulphated and unsulphated bile acids in serum, bile, and urine of patients with cholestasis. Gut 1976; 17: 861-9
137. Stiehl A, Ast E, Czygan P, et al. Pool-size, synthesis, and turnover of sulfated and nonsulfaled cholic acid and chenodeoxycholic acid in patients with cirrhosis of the liver. Gastroenterology 1978; 74: 572-7
138. Crosignani A, Battezzati PM, Setchell KDR, et al. Effects of ursodeoxycholic acid on serum liver enzymes and bile acid metabolism in chronic active hepatitis: a dose-response study. Hepatology 1991; 13: 339-44
139. Podda M, Ghezzi C, Battezzati PM, et al. Effects of ursodeoxycholic acid and taurine on serum liver enzymes and bile acids in chronic hepatitis. Gastroenterology 1990; 98: 1044-50
140. McCormick WC III, Bell CC, Swell L, et al. Cholic acid synthesis as an index of the severity of liver disease in man. Gut 1973; 14: 895-902
141. Akashi Y, Miyazaki H, Yanagisawa J, et al. Bile acid metabolism in cirrhotic liver: tissue-altered synthesis and impaired hepatic secretion. Clin Chim Acta 1987; 168: 199-206
142. Di Sant'Agnese PA, Davies PB. Cystic Fibrosis in adults: 75 cases and a review of 232 cases in the literature. Am J Med 1979; 66: 121-32
143. Roy CC, Weber AM, Morin CL, et al. Hepatobiliary disease in cystic fibrosis: a survey of current issues and concepts. J Pediatr Gastroenterol Nutr 1982; 1: 469-78
144. Colombo C, Crosignani A, Apostolo MG, et al. Oral bile acids in cystic fibrosis associated liver disease. J R Soc Med 1994; 87 Suppl. 21: 20-4
145. Weber AM, Roy CC, Morin CL, et al. Malabsorption of bile acids in children with cystic fibrosis. N Engl J Med 1973; 289: 1001-5
146. Colombo C, Setchell KDR, Podda M, et al Effects of ursodeoxycholic acid therapy for liver disease associated with cystic fibrosis. J Pediatr 1990; 117: 482-9
147. Colombo C, Crosignani A, Assaisso M, et al. Ursodeoxycholic acid therapy in cystic fibrosis-associated liver disease: a dose-response study. Hepatology 1992; 16: 924-30
148. Nakagawa M, Colombo C, Setchell KDR. Comprehensive study of the biliary bile acid composition of patients with cystic fibrosis and associated liver disease before and after UDCA administration. Hepatology 1990; 12: 322-34
149. Colombo C, Roda A, Roda E, et al. Evaluation of an oral ursodeoxycholic acid load in the assessment of bile acid malabsorption in cystic fibrosis. Dig Dis Sci 1983; 28: 306-11
150. Setchell KDR, O'Connell N, Bern E, et al. Markedly decreased biliary ursodeoxycholic acid (UDCA) enrichment with high doses UDCA in cystic fibrosis (CF) associated liver disease: optimization of the therapeutic dose [abstract]. Hepatology 1994; 20: 262A
151. Thompson GN. Excessive fecal taurine loss predisposes to taurine deficiency in cystic fibrosis. J Pediatr Gastroenterol Nutr 1988; 7: 214-9
152. Colombo C, Arlati S, Curcio L, et al. Effect of taurine supplementation on fat and bile acid absorption in patients with cystic fibrosis. Scand J Gastroenterol 1988; 23 Suppl. 143: 151-6
153. Darling PB, Lepage G, Leroy C, et al. Effect of taurine supplements on fat absorption in cystic fibrosis. Pediatr Res 1985; 19: 578-82
154. Colombo C, Podda M, Battezzati PM, et al. Ursodeoxycholic acid for cystic fibrosis-associated liver disease: final report of a mullicenter trial [abstract]. Hepatology 1993; 18: 142A
155. Lillienau J, Schteingart CD, Hofmann AF. Physicochemical and physiological properties of cholylsarcosine. A potential replacement detergent for bile acid deficiency states in the small intestine. J Clin Invest 1992; 89: 420-31
156. Schmassmann A, Angellotti MA, Ton-Nu HT, et al. Transport, metabolism, and effect of chronic feeding of cholylsarcosine, a conjugated bile acid resistant to deconjugation and dehydroxylation. Gastroenterology 1990; 98: 163-74