Comprehensive Physiology Wiley Online Library
For Librarians For Authors Editors About

Biliary Excretion

Curtis D. Klaassen

10.1002/cphy.cp090134

Source: Supplement 26: Handbook of Physiology, Reactions to Environmental Agents

Originally published: 1977

Published online: January 2011

Full Article on Wiley Online Library



Abstract

The sections in this article are:

1 Bile Production
2 Classification of Foreign Compounds Excreted Into Bile
3 Role of Ligandin in Hepatic Uptake
4 Polarity and Molecular Size in Biliary Excretion
5 “First‐Pass“ Effect
6 Species Differences in Biliary Excretion
7 Effect of Liver Injury on Biliary Excretion
8 Effect of Microsomal Enzyme Inducers on Biliary Excretion
9 Biliary Excretion in the Newborn
10 Enterohepatic Circulation
11 Conclusion
Figure 1. Figure 1.

Effect of varying taurocholate excretion rate, during the course of a single study, on bile flow during cholinergic blockade.

From Preisig et al. 137
Figure 2. Figure 2.

Biliary mannitol clearance in ml/min (ordinate) plotted against rate of bile acid secretion. Solid regression lines (obtained by method of least squares) relate mannitol clearance C to rate R of bile acid secretion as follows: dog Ha, C = 0.10 + 0.0058R. Dashed lines show relationship between bile flow F and rate of bile acid secretion and have the following equation: dog Ha, F = 0.05 + 0.0055R.

From Wheeler et al. 177
Figure 3. Figure 3.

The X, Y, and Z sulfobromophthalein (BSP)‐binding protein fractions from 110,000‐g supernate from 2‐g rat liver containing 58 mg protein with 2.4 μmole BSP added in vitro and eluted from a column of Sephadex G75 (3.2 × 55 cm) at a flow rate of 32.8 ml/h. Collections were 4.9 ml/tube. Solid line, (left ordinate), optical density 280 nm; dashed line, (right ordinate), optical density 580 nm. Optical density at 280 nm indicates protein and at 580 nm after alkalinization indicates BSP.

From Levi et al. 111
Figure 4. Figure 4.

Threshold molecular weight for appreciable biliary excretion (10% of dose) in female rat.

From Hirom et al. 68
Figure 5. Figure 5.

Effect of bile duct ligation (BDL) on the plasma disappearance of diethylstilbestrol.

From Klaassen 91


Figure 1.

Effect of varying taurocholate excretion rate, during the course of a single study, on bile flow during cholinergic blockade.

From Preisig et al. 137


Figure 2.

Biliary mannitol clearance in ml/min (ordinate) plotted against rate of bile acid secretion. Solid regression lines (obtained by method of least squares) relate mannitol clearance C to rate R of bile acid secretion as follows: dog Ha, C = 0.10 + 0.0058R. Dashed lines show relationship between bile flow F and rate of bile acid secretion and have the following equation: dog Ha, F = 0.05 + 0.0055R.

From Wheeler et al. 177


Figure 3.

The X, Y, and Z sulfobromophthalein (BSP)‐binding protein fractions from 110,000‐g supernate from 2‐g rat liver containing 58 mg protein with 2.4 μmole BSP added in vitro and eluted from a column of Sephadex G75 (3.2 × 55 cm) at a flow rate of 32.8 ml/h. Collections were 4.9 ml/tube. Solid line, (left ordinate), optical density 280 nm; dashed line, (right ordinate), optical density 580 nm. Optical density at 280 nm indicates protein and at 580 nm after alkalinization indicates BSP.

From Levi et al. 111


Figure 4.

Threshold molecular weight for appreciable biliary excretion (10% of dose) in female rat.

From Hirom et al. 68


Figure 5.

Effect of bile duct ligation (BDL) on the plasma disappearance of diethylstilbestrol.

From Klaassen 91
References
 1. Abou‐el‐Makarem, M. M., P. Millburn, R. L. Smith, and R. T. Williams. Biliary excretion of foreign compounds. Benzene and its derivatives in the rat. Biochem. J. 105: 1269–1274, 1967.
 2. Abou‐el‐Makarem, M. M., P. Millburn, R. L. Smith, and R. T. Williams. Biliary excretion of foreign compounds. Species differences in biliary excretion. Biochem. J. 105: 1289–1293, 1967.
 3. Abshagen, U., K. V. Bergmann, and N. Rietbrock. Evaluation of the enterohepatic circulation after 3H‐digoxin administration in the rat. Naunyn‐Schmiedebergs Arch. Pharmacol. 275: 1–10, 1972.
 4. Alpert, S., M. Mosher, A. Shanske, and I. M. Arias. Multiplicity of hepatic excretory mechanisms for organic anions. J. Gen. Physiol. 53: 238–247, 1969.
 5. Arias, I. M., L. M. Gartner, M. Cohen, J. Ben Ezzer, and A. J. Levi. Chronic nonhemolytic unconjugated hyperbilirubinemia with glucuronyl transferase deficiency. Clinical, biochemical, pharmacologic and genetic evidence for heterogeneity. Am. J. Med. 47: 395–409, 1969.
 6. Arias, I. M., L. Johnson, and S. Wolfson. Biliary excretion of injected conjugated and unconjugated bilirubin by normal and Gunn rats. Am. J. Physiol. 200: 1091–1094, 1961.
 7. Ashton, M. J., B. Clark, K. M. Jones, G. F. Moss, M. G. Neale, and J. T. Ritchie. The absorption, metabolism and excretion of disodium chromoglycate in nine animal species. Toxicol. Appl. Pharmacol. 26: 319–328, 1973.
 8. Bernstein, G., S. A. Artz, J. Hasen, and J. H. Oppenheimer. Hepatic accumulation of 125I‐thyroxine in the rat: Augmentation by phenobarbital and chlordane. Endocrinology 82: 406–409, 1968.
 9. Bernstein, L. H., J. Ben Ezzer, L. Gartner, and I. M. Arias. Hepatic intracellular distribution of tritium‐labeled unconjugated and conjugated bilirubin in normal and Gunn rats. J. Clin. Invest. 45: 1194–1201, 1966.
 10. Berthelot, P., S. Erlinger, D. Dhumeaux, and A.‐M. Preaux. Mechanism of phenobarbital‐induced hypercholeresis in the rat. Am. J. Physiol. 219: 809–813, 1970.
 11. Bertinchamps, A. J., S. T. Miller, and G. C. Cotzias. Interdependence of routes excreting manganese. Am. J. Physiol. 211: 217–224, 1966.
 12. Billing, B. H., Q. Maggiore, and M. A. Carter. Hepatic transport of bilirubin. Ann. NY Acad. Sci. 111: 319–325, 1963.
 13. Blaxter, K. L., and A. T. Cowie. Excretion of lead in the bile. Nature 157: 588, 1946.
 14. Boyer, J. L. Canalicular bile formation in the isolated perfused rat liver. Am. J. Physiol. 221: 1156–1163, 1971.
 15. Boyer, J. L., and G. Klatskin. Canalicular bile flow and bile secretory pressure. Evidence for a non‐bile salt dependent fraction in the isolated perfused rat liver. Gastroenterology 59: 853–859, 1970.
 16. Boyes, R. N., H. J. Adams, and B. R. Duce. Oral absorption and disposition kinetics of lidocaine hydrochloride in dogs. J. Pharmacol. Exptl. Therap. 174: 1–8, 1970.
 17. Branch, R. A., D. G. Shand, and A. S. Nies. Hemodynamic drug interactions: The reduction of oxyphenbutazone clearance by dl‐propranol in the dog. J. Pharmacol. Exptl. Therap. 187: 133–137, 1973.
 18. Brauer, R. W. Mechanims of bile secretion. J. Am. Med. Assoc. 169: 1462–1466, 1959.
 19. Brauer, R. W., G. F. Leong, and R. J. Holloway. Mechanics of bile secretion: Effect of perfusion pressure and temperature on bile flow and bile secretion pressure. Am. J. Physiol. 177: 103–112, 1954.
 20. Brown, W. R., G. M. Grodsky, and J. V. Carbone. Intracellular distribution of tritiated bilirubin during hepatic uptake and excretion. Am. J. Physiol. 207: 1237–1241, 1964.
 21. Caldwell, J. H., and N. J. Greenberger. Interruption of the enterohepatic circulation of digitoxin by cholestyramine. J. Clin. Invest. 50: 2626–2637, 1971.
 22. Castellino, N., and S. Aloj. Kinetics of the distribution and excretion of lead in the rat. Brit. J. Ind. Med. 21: 308–314, 1964.
 23. Castle, M. C., and G. L. Lage. Enhanced biliary excretion of digitoxin following spironolactone as it relates to the prevention of digitoxin toxicity. Res. Commun. Chem. Pathol. Pharmacol. 5: 99–108, 1973.
 24. Castle, M. C., and G. L. Lage. Excretion of 3H‐digitoxin and its metabolites following spironolactone pretreatment in rats. Drug Metab. Disposition 1: 590–597, 1973.
 25. Catz, C., and S. J. Yaffe. Pharmacological modification of bilirubin conjugation in the newborn. Am. J. Diseases Children 104: 516–517, 1962.
 26. Catz, C., and S. J. Yaffe. Barbiturate enhancement of bilirubin conjugation and excretion in young and adult animals. Pediat. Res. 2: 361–370, 1968.
 27. Charytan, C. The enterohepatic circulation in glutethimide intoxication. Clin. Pharmacol. Therap. 11: 816–820, 1970.
 28. Cikrt, M. Biliary excretion of 203Hg, 64Cu, 52Mn, and 210Pb in the rat. Brit. J. Ind. Med. 29: 74‐80, 1972.
 29. Cikrt, M. Enterohepatic circulation of 64Cu, 52Mn and 203Hg in rats. Arch. Toxikol. 31: 51–59, 1973.
 30. Clarkson, T. W., H. Small, and T. Norseth. Excretion and absorption of methyl mercury after polythiol resin treatment. Arch. Environ. Health 26: 173–176, 1973.
 31. Conney, A. H. Pharmacological implications of microsomal enzyme induction. Pharmacol. Rev. 19: 317–366, 1967.
 32. Cornelius, C. E., and R. R. Gronwall. Congenital photosensitivity and hyperbilirubinemia in Southdown sheep in the United States. Am. J. Vet. Res. 29: 291–295, 1968.
 33. Cox, E., and S. E. Wright. The hepatic excretion of digitalis glycosides and their genins in the rat. J. Pharmacol. Exptl. Therap. 126: 117–123, 1959.
 34. Crigler, J. F., Jr., and N. I. Gold. Sodium phenobarbitalinduced decrease in serum bilirubin in an infant with congenital nonhemolytic jaundice and kernicterus. J. Clin. Invest. 45: 998, 1966.
 35. Crigler, J. F., Jr., and N. I. Gold. Effect of sodium phenobarbital on the metabolism of bilirubin 3H and l4C in an infant with congenital nonhemolytic jaundice and kernicterus. J. Clin. Invest. 46: 1047, 1967.
 36. Crigler, J. F., Jr., and N. I. Gold. Effect of sodium phenobarbital on bilirubin metabolism in an infant with congenital, nonhemolytic, unconjugated hyperbilirubinemia, and kernicterus. J. Clin. Invest. 48: 42–55, 1969.
 37. Cunningham, M. D., J. W. Mace, and E. R. Peters. Clinical experience with phenobarbitone in icterus neonatorum. Lancet 1: 550–551, 1969.
 38. DeLeon, A., L. M. Gartner, and I. M. Arias. The effect of phenobarbital on hyperbilirubinemia in glucuronyl transferase deficient rats. J. Lab. Clin. Med. 70: 273–278, 1967.
 39. Despopoulos, A. Renal and hepatic transport of food dyes. J. Pharmacol. Exptl. Therap. 163: 222–228, 1968.
 40. Despopoulos, A. Congruence of renal and hepatic excretory functions: sulfonic acid dyes. Am. J. Physiol. 220: 1755–1758, 1971.
 41. Despopoulos, A., and H. Sonnenberg. Congruence of excretory functions of liver and kidney: sulfonamides. Am. J. Physiol. 212: 1117–1122, 1967.
 42. Erlinger, S., D. Dhumeaux, P. Berthelot, and M. Dumont. Effect of inhibitors of sodium transport on bile formation in the rabbit. Am. J. Physiol. 219: 416‐422, 1970.
 43. Farah, A. On the elimination of G‐strophanthin by the rat. J. Pharmacol. Exptl. Therap. 86: 248–257, 1946.
 44. Fischer, L. J., and P. Millburn. Stilboestrol transport and glucuronide formation in everted sacs of rat intestine. J. Pharmacol. Exptl. Therap. 175: 267–275, 1970.
 45. Fleischner, G., J. Robbins, and I. M. Arias. Immunological studies of Y protein. A major cytoplasmic organic anionbinding protein in rat liver. J. Clin. Invest. 51: 677–684, 1972.
 46. Forker, E. L. Two sites of bile formation as determined by mannitol and erythritol clearance in the guinea pig. J. Clin. Invest. 48: 1189–1195, 1967.
 47. Forker, E. L., T. Hicklin, and H. Sornson. The clearance of mannitol and erythritol in rat bile. Proc. Soc. Exptl. Biol. Med. 126: 115–119, 1967.
 48. Fujimoto, J. M., W. F. Eich, and H. R. Nichols. Enhanced sulfobromophthalein disappearance in mice pretreated with various drugs. Biochem. Pharmacol. 14: 515–524, 1965.
 49. Gibaldi, M., R. N. Boyes, and S. Feldman. Influence of first‐pass effect on availability of drugs on oral administration. J. Pharm. Sci. 9: 1338–1340, 1971.
 50. Gibaldi, M., and S. Feldman. Route of administration and drug metabolism. European J. Pharmacol. 19: 323–329, 1972.
 51. Gibson, J. E., and B. A. Becker. Demonstration of enhanced lethality of drugs in hypoexcretory animals. J. Pharm. Sci. 56: 1503–1505, 1967.
 52. Gigon, P. L., P. K. Nayak, and L. S. Schanker. Transport and binding of chloroguanide‐triazine by rat liver slices. Proc. Soc. Exptl. Biol. Med. 132: 1103–1109, 1969.
 53. Goldstein, J. A., and A. Taurog. Enhanced biliary excretion of thyroxine glucuronide in rats pretreated with benzpyrene. Biochem. Pharmacol. 17: 1049–1065, 1968.
 54. Graf, J., P. Korn, and M. Peterlik. Mechanism of bile formation in the isolated perfused rat liver: Influence of changes in the ionic composition of the perfusion medium. In: Isolated Liver Perfusion and Its Applications, edited by I. Bartosek, A. Guaitani, and L. L. Miller. Hewlett, N.Y.: Raven Press, 1973, p. 271‐276.
 55. Greenberg, D. M., D. H. Copp, and E. M. Cuthbertson. Studies in mineral metabolism with the aid of artificial radioactive isotopes. VII. The distribution and excretion, particularly by way of the bile, of iron, cobalt, and manganese. J. Biol. Chem. 147: 749–756, 1943.
 56. Greenberger, N. J., and F. B. Thomas. Biliary excretion of 3H‐digitoxin: Modification by bile salts and phenobarbital. J. Lab. Clin. Med. 81: 241–251, 1973.
 57. Grodsky, G. M., H. J. Kolb, R. E. Fanska, and C. Nemechek. Effect of age of rat on development of hepatic carriers for bilirubin: A possible explanation for physiologic jaundice and hyperbilirubinemia in the newborn. Metabolism Clin. Exptl. 19: 246–252, 1970.
 58. Haddock, E. P., E. J. Zapolski, M. Rubin, and J. V. Princiotto. Biliary excretion of chelated iron. Proc. Soc. Exptl. Biol. Med. 120: 663–668, 1965.
 59. Hammaker, L., and R. Schmid. Interference with bile pigment uptake in the liver by flavaspidic acid. Gastroenterology 53: 31–37, 1967.
 60. Hanahan, D. J., E. G. Daskalakis, T. Edwards, and H. J. Dauben, Jr.. The metabolic pattern of C14‐diethylstilbestrol. Endrocrinology 53: 163–170, 1953.
 61. Harbison, R. D., and J. L. Spratt. Disappearance of plasma bilirubin fractions in the rat after phenobarbital. Arch. Intern. Pharmacodyn. 172: 32–36, 1968.
 62. Hardwicke, J., J. G. Rankin, K. J. Baker, and R. Preisig. The loss of protein in human and canine hepatic bile. Clin. Sci. 26: 509–517, 1964.
 63. Hargreaves, T., and G. H. Lathe. Inhibitory aspects of bile secretion. Nature 200: 1172–1176, 1963.
 64. Hart, L. G., A. M. Guarino, and R. H. Adamson. Effects of phenobarbital on biliary excretion of organic acids in male and female rats. Am. J. Physiol. 217: 46–52, 1969.
 65. Hart, L. G., and L. S. Schanker. Active transport of cholorothiazide into bile. Am. J. Physiol. 211: 643–646, 1966.
 66. Hirom, P. C., P. Millburn, R. L. Smith, and R. T. Williams. Studies on the relationship between molecular structure and the biliary excretion of organic compounds. Biochem. J. 113: 27–28P, 1969.
 67. Hirom, P. C., P. Millburn, R. L. Smith, and R. T. Williams. Molecular weight and chemical structure as factors in the biliary excretion of sulphonamides in the rat. Xenobiotica 2: 205–214, 1972.
 68. Hirom, P. C., P. Millburn, R. L. Smith, and R. T. Williams. Species variations in the threshold molecular‐weight factor for biliary excretion of organic anions. Biochem. J. 129: 1071–1077, 1972.
 69. Hunter, A., and C. D. Klaassen. Species difference in the plasma disappearance and biliary excretion of procaine amide ethobromide. Proc. Soc. Exptl. Biol. Med. 139: 1445–1450, 1972.
 70. Hunter, A., and C. D. Klaassen. Toxicity and excretion of colchicine in newborn rats. Pharmacologist 15: 51, 1973.
 71. Jávor, T., Á. Gógl, T. HorvÁth, and I. Tényi. Effects of phenobarbital treatment on biliary excretion in man. Drug Metab. Disposition 1: 424–427, 1973.
 72. Jirsa, M., J. P. Dickinson, and G. H. Lathe. Effect on bilirubin excretion of blocking the carboxyl sites of glucuronide conjugation by methylation. Nature 220: 1322–1334, 1968.
 73. Juhlin, L. Excretion of intravenously injected solid particles in bile. Acta Physiol. Scand. 49: 224–230, 1960.
 74. Kaplowitz, N., I. W. Percy‐Robb, and N. B. Javitt. Glutathione S‐aryltransferase: Purified hepatic enzyme with properties identical to ligandin. Gastroenterology 65: 549, 1973.
 75. Katzung, B. G., and F. H. Meyers. Excretion of radioactive digitoxin by the dog. J. Pharmacol. Exptl. Therap. 149: 257–262, 1965.
 76. Katzung, B. G., and F. H. Meyers. Biotransformation of digitoxin in the dog. J. Pharmacol. Exptl. Therap. 154: 575–580, 1966.
 77. Kent, T. H., L. J. Fischer, and R. Marr. Glucuronidase activity in intestinal contents of rat and man and relationship to bacterial flora. Proc. Soc. Exptl. Biol. Med. 140: 590–594, 1972.
 78. Klaassen, C. D. Biliary flow after microsomal enzyme induction. J. Pharmacol. Exptl. Therap. 168: 218–223, 1969.
 79. Klaassen, C. D. Effects of phenobarbital on the plasma disappearance and biliary excretion of drugs in rats. J. Pharmacol. Exptl. Therap. 175: 289–300, 1970.
 80. Klaassen, C. D. Plasma disappearance and biliary excretion of sulfobromophthalein and phenol‐3,6‐dibromphthal‐ein disulfate after microsomal enzyme induction. Biochem. Pharmacol. 19: 1241–1249, 1970.
 81. Klaassen, C. D. Biliary excretion of barbiturates. Brit. J. Pharmacol. 43: 161–166, 1971.
 82. Klaassen, C. D. Does bile acid secretion determine canalicular bile production in rats? Am. J. Physiol. 220: 667–673, 1971.
 83. Klaassen, C. D. Gas‐liquid chromatographic determination of bile acids in bile. Clin. Chim. Acta. 35: 225–229, 1971.
 84. Klaassen, C. D. Studies on the increased biliary flow produced by phenobarbital in rats. J. Pharmacol. Exptl. Therap. 176: 743–751, 1971.
 85. Klaassen, C. D. Immaturity of the newborn rats hepatic excretory function for ouabain. J. Pharmacol. Exptl. Therap. 183: 520–526, 1972.
 86. Klaassen, C. D. Species differences in the choleretic response to bile salts. J. Physiol. London 224: 259–269, 1972.
 87. Klaassen, C. D. Bile flow and composition during bile acid depletion and administration. Can. J. Physiol. Pharmacol. 52: 334–348, 1973.
 88. Klaassen, C. D. Comparison of the choleretic properties of bile acids. European J. Pharmacol. 23: 270–275, 1973.
 89. Klaassen, C. D. Comparison of the toxicity of chemicals in newborn rats, to bile duct‐ligated and sham‐operated rats and mice. Toxicol. Appl. Pharmacol. 24: 37–44, 1973.
 90. Klaassen, C. D. Effect of alteration in body temperature on the biliary excretion of copper. Proc. Soc. Exptl. Biol. Med. 144: 8–12, 1973.
 91. Klaassen, C. D. The effect of altered hepatic function on the toxicity, plasma disappearance and biliary excretion of diethylstilbestrol. Toxicol. Appl. Pharmacol. 24: 142–149, 1973.
 92. Klaassen, C. D. The effect of spironolactone and other microsomal enzyme inducers on the plasma disappearance and biliary excretion of cardiac glycosides. Gastroenterology 65: 551, 1973.
 93. Klaassen, C. D. Hepatic excretory function in the newborn rat. J. Pharmacol. Exptl. Therap. 184: 721–728, 1973.
 94. Klaassen, C. D., Immaturity of the hepatic excretory function for ouabain. In: The Liver: Quantitative Aspects of Structure and Function, edited by G. Paumgartner and R. Preisig. Basel: Karger, 1973, p. 402‐409.
 95. Klaassen, C. D. Metabolism and biliary excretion of ethacrynic acid. Pharmacologist 15: 523, 1973.
 96. Klaassen, C. D. Biliary excretion of arsenic in rats, rabbits and dogs. Toxicol. Appl. Pharmacol. 29: 447–457, 1974.
 97. Klaassen, C. D. Biliary excretion of manganese in rats, rabbits and dogs. Toxicol. Appl. Pharmacol. 29: 458–468, 1974.
 98. Klaassen, C. D. Stimulation of the development of the hepatic excretory mechanism for ouabain in newborn rats with microsomal enzyme inducers. J. Pharmacol. Exptl. Therap. 191: 212–218, 1974.
 99. Klaassen, C. D., and G. L. Plaa. Relative effects of various chlorinated hydrocarbons on liver and kidney function in mice. Toxicol. Appl. Pharmacol. 9: 139–151, 1966.
 100. Klaassen, C. D., and G. L. Plaa. Species variation in metabolism, storage, and excretion of sulfobromophthalein. Am. J. Physiol. 213: 1322–1326, 1967.
 101. Klaassen, CD., and G. L. Plaa. Effect of carbon tetrachloride on the metabolism, storage, and excretion of sulfobromophthalein. Toxicol. Appl. Pharmacol. 12: 132–139, 1968.
 102. Klaassen, C. D., and G. L. Plaa. Hepatic disposition of phenoldibromphthalein disulfonate and sulfobromophthalein. Am. J. Physiol. 215: 971–976, 1968.
 103. Klaassen, C. D., and G. L. Plaa. Studies on the mechanism of phenobarbital‐enhanced sulfobromophthalein disappearance. J. Pharmacol. Exptl. Therap. 161: 361–366, 1968.
 104. Klaassen, C. D., and G. L. Plaa. Plasma disappearance and biliary excretion of indocyanine green in rats, rabbits and dogs. Toxicol. Appl. Pharmacol. 15: 374–384, 1969.
 105. Klaassen, C. D., and D. W. Shoeman. Biliary excretion of lead in rats, rabbits, and dogs. Toxicol. Appl. Pharmacol. 29: 434–446, 1974.
 106. Kreek, M. J., and M. H. Sleisenger. Reduction of serum‐unconjugated‐bilirubin with phenobarbitone in adult congenital non‐haemolytic unconjugated hyperbilirubinaemia. Lancet 2: 73–78, 1968.
 107. Kupferberg, H. J. Inhibition of ouabain‐H3 uptake by liver slices and its excretion into the bile by compounds having a steroid nucleus. Life Sci., Part 1 8: 1179–1185, 1969.
 108. Kupferberg, H. J., and L. S. Schanker. Biliary secretion of ouabain‐3H and its uptake by liver slices in the rat. Am. J. Physiol. 214: 1048–1053, 1968.
 109. Lanman, R. C., and L. S. Schanker. Rapid passage of mannitol into liver and bile. Life Sci., Part 1 9: 1003–1010, 1970.
 110. Levi, A. J., Z. Gatmaitan, and I. M. Arias. Deficiency of hepatic organic anion‐binding protein as a possible cause of non‐haemolytic unconjugated hyperbilirubinaemia in the newborn. Lancet 2: 139–140, 1969.
 111. Levi, A. J., Z. Gatmaitan, and I. M. Arias. Two hepatic cytoplasmic protein fractions, Y and Z, and their possible role in the hepatic uptake of bilirubin, sulfobromophthalein, and other anions. J. Clin. Invest. 48: 2156–2167, 1969.
 112. Levi, A. J., Z. Gatmaitan, and I. M. Arias. Deficiency of hepatic organic anion‐binding protein, impaired organic anion uptake by liver and “physiologic” jaundice in newborn monkeys. New Engl. J. Med. 283: 1136–1139, 1970.
 113. Levine, R. I., H. Reyes, A. J. Levi, Z. Gatmaitan, and I. M. Arias. Phylogenetic study of organic anion transfer from plasma into the liver. Nature New Biol. 231: 277–279, 1971.
 114. Levine, W. G. The role of microsomal drug‐metabolizing enzymes in the biliary excretion of 3,4‐benzpyrene in the rat. J. Pharmacol. Exptl. Therap. 175: 301–310, 1970.
 115. Levine, W. G. Biliary excretion of 3‐methylcholanthrene as controlled by its metabolism. J. Pharmacol. Exptl. Therap. 183: 420–426, 1972.
 116. Levine, W. G., P. Millburn, R. L. Smith, and R. T. Williams. The role of the hepatic endoplasmic reticulum in the biliary excretion of foreign compounds by the rat. The effect of phenobarbitone and SKF 525‐A (diethylaminoethyl diphenylpropylacetate). Biochem. Pharmacol. 19: 235–244, 1970.
 117. Litwack, G., B. Ketterer, and I. M. Arias. Ligandin: a hepatic protein which binds steroids, bilirubin, carcinogens and a number of exogenous organic anions. Nature 234: 466–467, 1971.
 118. Maurer, H. M., J. A. Wolff, M. Finster, P. J. Poppers, E. Pantuck, R. Kuntzman, and A. H. Conney. Reduction in concentration of total serum‐bilirubin in offspring of women treated with phenobarbitone during pregnancy. Lancet 2: 122‐124, 1968.
 119. Meijer, D. K. F., J. W. Arends, and J. G. Weitering. The cardiac glycoside sensitive step in the hepatic transport of the bisquaternary ammonium compound, hexafluorenium. European J. Pharmacol. 15: 245–251, 1971.
 120. Meijer, D. K. F., E. S. Bos, and K. J. van der Laan. Hepatic transport of mono and bisquaternary ammonium compounds. European J. Pharmacol. 11: 371–377, 1970.
 121. Meijer, D. K. F., J. Wester, and M. Gunnink. Distribution of quaternary ammonium compounds between particulate and soluble constituents of rat liver, in relation to their transport from plasma into bile. Naunyn‐Schmiedebergs Arch. Pharmacol. 273: 179–192, 1972.
 122. Millburn, P., R. L. Smith, and R. T. Williams. Biliary excretion of foreign compounds. Biphenyl, stilboestrol and phenolphthalein in the rat: Molecular weight, polarity and metabolism as factors in biliary excretion. Biochem. J. 105: 1275–1281, 1967.
 123. Millburn, P., R. L. Smith, and R. T. Williams. Biliary excretion of foreign compounds. Sulphonamide drugs in the rat. Biochem. J. 105: 1283–1287, 1967.
 124. Nahrwold, D. L., and M. I. Grossman. Secretion of bile in response to food with and without bile in the intestine. Gastroenterology 53: 11–17, 1967.
 125. Nayak, P. K., and L. S. Schanker. Active transport of tertiary amine compounds into bile. Am. J. Physiol. 217: 1639–1643, 1969.
 126. Nies, A. S., G. H. Evans, and D. G. Shand. The hemodynamic effects of beta adrenergic blockade on the flow‐dependent hepatic clearance of propranolol. J. Pharmacol. Exptl. Therap. 184: 716–720, 1973.
 127. Ohnhaus, E. E., S. S. Thorgeirsson, D. S. Da vies, and A. Breckenridge. Changes in liver blood flow during enzyme induction. Biochem. Pharmacol. 20: 2561–2570, 1971.
 128. Okita, G. T. Species difference in duration of action of cardiac glycosides. Federation Proc. 26: 1125–1130, 1967.
 129. Okita, G. T., P. J. Talso, J. H. Curry, Jr., F. D. Smith, Jr., and E. M. K. Geiling. Metabolic fate of radioactive digitoxin in human subjects. J. Pharmacol. Exptl. Therap. 115: 371–379, 1955.
 130. Oppenheimer, J. H., G. Bernstein, and M. I. Surks. Increased thyroxine turnover and thyroidal function after stimulation of hepatocellular binding of thyroxine by phenobarbital. J. Clin. Invest. 47: 1399–1406, 1968.
 131. Owen, C. A., Jr.. Absorption and excretion of Cu64‐labeled copper by the rat. Am. J. Physiol. 207: 1203–1206, 1964.
 132. Papavasiliou, P. S., S. T. Miller, and G. C. Cotzias. Role of liver in regulating distribution and excretion of manganese. Am. J. Physiol. 211: 211–216, 1966.
 133. Paumgartner, G., W. Horak, P. Probst, and G. Grabner. Effect of phenobarbital on bile flow and bile salt excretion in the rat. Naunyn‐Schmiedebergs Arch. Pharmakol. 270: 98–101, 1971.
 134. Peterson, R. E., and J. M. Fujimoto. Biliary excretion of morphine‐3‐glucuronide and morphine‐3‐ethereal sulfate by different pathways in the rat. J. Pharmacol. Exptl. Therap. 184: 409–418, 1973.
 135. Potrepka, R. F., and J. L. Spratt. Effect of phenobarbital and 3‐methylcholanthrene pretreatment on guinea pig hepatic microsomal bilirubin glucuronyltransferase activity. Biochem. Pharmacol. 20: 861–867, 1971.
 136. Preisig, R., H. Bucher, H. Stirnemann, and J. Tauber. Postoperative choleresis following bile duct obstruction in man. Rev. Franc. Etudes Clin. Biol. 14: 151–158, 1969.
 137. Preisig, R., H. L. Cooper, and H. O. Wheeler. The relationship between taurocholate secretion rate and bile production in the unanesthetized dog during cholinergic blockade and during secretin administration. J. Clin. Invest. 41: 1152–1162, 1962.
 138. Priestly, B. G., and G. L. Plaa. Temporal aspects of carbon tetrachloride‐induced alteration of sulfobromophthalein excretion and metabolism. Toxicol. Appl. Pharmacol. 17: 786–794, 1970.
 139. Pugh, P. M., and S. L. Stone. The effect of 2,4‐dinitrophe‐nol and related compounds on bile secretion. J. Physiol. London 198: 39–49, 1968.
 140. Ramboer, C., R. P. H. Thompson, and R. Williams. Controlled trials of phenobarbitone therapy of neonatal jaundice. Lancet 1: 966–968, 1969.
 141. Rawson, A. J. Human bile proteins. I. Proteins identified by antibody to human serum. Clin. Chem. 8: 310–317, 1962.
 142. Redinger, R. N., and D. M. Small. Primate biliary physiology VIII. The effect of phenobarbital upon bile salt synthesis and pool size, biliary lipid secretion, and bile composition. J. Clin. Invest. 52: 161–172, 1973.
 143. Reuning, R. H., and L. S. Schanker. Effect of carbon tetrachloride‐induced liver damage on hepatic transport of ouabain in the rat. J. Pharmacol. Exptl. Therap. 178: 589–594, 1971.
 144. Reuning, R. H., and L. S. Schanker. Effect of carbon tetrachloride‐induced liver damage on organic ion transport in rat liver. Toxicol. Appl. Pharmacol. 23: 553–562, 1972.
 145. Reyes, H., A. J. Levi, Z. Gatmaitan, and I. M. Arias. Organic anion‐binding protein in rat liver: Drug induction and its physiologic consequence. Proc. Natl. Acad. Sci. US 64: 168–170, 1969.
 146. Reyes, H., A. J. Levi, Z. Gatmaitan, and I. M. Arias. Studies of Y and Z, two hepatic cytoplasmic organic anion‐binding proteins: Effect of drugs, chemicals, hormones, and cholestasis. J. Clin. Invest. 50: 2242–2252, 1971.
 147. Roberts, R. J., and G. L. Plaa. Effect of phenobarbital on the excretion of exogenous bilirubin load. Biochem. Pharmacol. 16: 827–835, 1967.
 148. Robinson, S. H. Increased bilirubin conjugation in heterozygous Gunn rats treated with phenobarbital. Nature 222: 990–991, 1969.
 149. Robinson, S. H., C. Yannoni, and S. Nagasawa. Bilirubin excretion in rats with normal and impaired bilirubin conjugation: Effect of phenobarbital. J. Clin. Invest. 50: 2606–2613, 1971.
 150. Rosenthal, W. S., K. Kubo, M. Dolinski, J. Marino, W. L. Mersheimer, and G. B. J. Glass. The passage of serum albumin into bile in man. Am. J. Digest. Diseases 10: 271–283, 1965.
 151. Russell, J. Q., and C. D. Klaassen. Species variation in the biliary excretion of ouabain. J. Pharmacol. Exptl. Therap. 183: 513–519, 1972.
 152. Russell, J. Q., and C. D. Klaassen. Biliary excretion of cardiac glycosides. J. Pharmacol. Exptl. Therap. 186: 455–462, 1973.
 153. Schanker, L. S., Hepatic transport of organic cations. In: The Biliary System, edited by W. Taylor. Philadelphia: Davis, 1965, p. 469‐480.
 154. Schanker, L. S., Secretion of organic compounds in bile. In: Handbook of Physiology. Alimentary Canal, edited by C. F. Code. Washington D.C.: Am. Physiol. Soc., 1968, sect. 6, vol. 5, ch. 114, p. 2433‐2449.
 155. Schanker, L. S., and C. A. M. Hogben. Biliary excretion of inulin, sucrose, and mannitol: analysis of bile formation. Am. J. Physiol. 200: 1087–1090, 1961.
 156. Schanker, L. S., and H. M. Solomon. Active transport of quaternary ammonium compounds into bile. Am. J. Physiol. 204: 829–832, 1963.
 157. Schersten, T., S. Nilsson, E. Cahlin, M. Filipson, and G. Brodin‐Persson. Relationship between the biliary excretion of bile acids and the excretion of water, lecithin, and cholesterol in man. European J. Clin. Invest. 1: 242–247, 1971.
 158. Shand, D. G., G. H. Evans, and A. S. Nies. The almost complete hepatic extraction of propranolol during intravenous administration in the dog. Life. Sci. Part 1 10: 1417–1421, 1971.
 159. Shand, D. G., R. E. Rangno, and G. H. Evans. The disposition of propranolol. II. Hepatic elimination in the rat. Pharmacology 8: 344–352, 1972.
 160. Shaw, H., I. Caple, and T. Heath. Effect of ethacrynic acid on bile formation in sheep, dogs, rats, guinea pigs and rabbits. J. Pharmacol. Exptl. Therap. 182: 27–33, 1972.
 161. Smith, R. L. The biliary excretion and enterohepatic circulation of drugs and other organic compounds. Progr. Drug Res. 9: 299–360, 1966.
 162. Smith, R. L. Species differences in the biliary excretion of drugs. Proc. European Soc. Study Drug Toxicity 11: 19–32, 1970.
 163. Smith, R. L., Excretion of drugs in bile. In: Concepts in Biochemical Pharmacology I, edited by B. B. Brodie and J. R. Gilette. New York: Springer‐Verlag, 1971, vol. 28, p. 354‐385. (Handbook of Exptl. Pharmacol.).
 164. Solomon, H. M., and L. S. Schanker. Hepatic transport of organic cations: active uptake of a quaternary ammonium compound, procaine amide ethrobromide, by rat liver slices. Biochem. Pharmacol. 12: 621–626, 1963.
 165. Sperber, I. Secretion of organic anions in the formation of urine and bile. Pharmacol. Rev. 11: 109–134, 1959.
 166. Sperber, I. Biliary excretion and choleresis. Proceedings International Pharmacology Meeting, 1st, Stockholm, August 1961 4: 137‐143, 1963.
 167. Sperber, I., Biliary secretion of organic anions and its influence on bile flow. In: The Biliary System, edited by W. Taylor. Philadelphia: Davis, 1965, p. 457‐467.
 168. Stowe, C. M., and G. L. Plaa. Extrarenal excretion of drugs and chemicals. Ann. Rev. Pharmacol. 8: 337–355, 1968.
 169. Thaler, M. M. Effect of phenobarbital on hepatic transport and excretion of 131I‐Rose Bengal in children with cholestasis. Pediat. Res. 6: 100–110, 1972.
 170. Thompson, R. Q., M. Sturtevant, O. D. Bird, and A. J. Glazko. The effect of metabolites of chloramphenicol (Chloromycetin) on the thyroid of the rat. Endocrinology 55: 665–681, 1954.
 171. Tichy, M., and M. Cikrt. Manganese transfer into the bile in rats. Arch. Toxikol. 29: 51–58, 1972.
 172. Trolle, D. Decrease of total serum‐bilirubin concentration in newborn infants after phenobarbitone treatment. Lancet 2: 705–708, 1968.
 173. Trolle, D. Phenobarbitone and neonatal icterus. Lancet 1: 251–252, 1968.
 174. Wheeler, H. O., Water and electrolytes in bile. In: Handbook of Physiology. Alimentary Canal, edited by C. F. Code. Washington, D.C.: Am. Physiol. Soc., 1968, sect. 6, vol. 5, chapt. 113, p. 2409‐2431.
 175. Wheeler, H. O., Secretion of bile. In: Diseases of the Liver, 3rd ed., edited by L. Schiff. Philadelphia: Lippincott, 1969, p. 84‐102.
 176. Wheeler, H. O., and O. L. Ramos. Determinants of the flow and composition of bile in the unanesthetized dog during constant infusions of sodium taurocholate. J. Clin. Invest. 39: 161–170, 1960.
 177. Wheeler, H. O., E. D. Ross, and S. E. Bradley. Canalicular bile production in dogs. Am. J. Physiol. 214: 866–874, 1968.
 178. Whelan, G., and B. Combes. Depression of biliary excretion of infused bilirubin in rats and guinea pigs by bile. Am. J. Physiol. 220: 683–687, 1971.
 179. Whelan, G., J. Hoch, S. Schenker, and B. Combes. Impaired hepatic disposition of sulfobromophthalein sodium in neonatal guinea pigs: Nature of the defect. J. Lab. Clin. Med. 76: 775–789, 1970.
 180. Whitsett, T. L., P. G. Dayton, and J. L. McNay. The effect of hepatic blood flow on the hepatic removal rate of oxyphenbutazone in the dog. J. Pharmacol. Exptl. Therap. 177: 246–255, 1971.
 181. Williams, R. T., P. Millburn, and R. L. Smith. The influence of enterohepatic circulation on toxicity of drugs. Ann. NY Acad. Sci. 123: 110–124, 1965.
 182. Yaffe, S. J., G. Levy, T. Matsuzawa, and T. Baliah. Enhancement of glucuronide‐conjugating capacity in a hyperbilirubinemic infant due to apparent enzyme induction by phenobarbital. New Engl. J. Med. 275: 1461–1466, 1966.
 183. Yeung, C Y., and V. Y. H. Yu. Phenobarbitone enhancement of bromsulphalein clearance in neonatal hyperbilirubinemia. Pediatrics 48: 556–561, 1971.
 184. Zsigmond, G., and B. Solymoss. Effect of spironolactone, pregnenolone‐16 α‐carbonitrile and Cortisol on the metabolism and biliary excretion of sulfobromophthalein and phenol‐3,6‐dibromophthalein disulfonate in rats. J. Pharmacol. Exptl. Therap. 183: 499–507, 1972.

Contact Editor

Submit a note to the editor about this article by filling in the form below.

* Required Field

Article Title: Biliary Excretion
 

How to Cite

Curtis D. Klaassen. Biliary Excretion. Compr Physiol 2011, Supplement 26: Handbook of Physiology, Reactions to Environmental Agents: 537-553. First published in print 1977. doi: 10.1002/cphy.cp090134