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Excretion of Xenobiotic Compounds in Bile

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The Hepatobiliary System

Part of the book series: NATO Advanced Study Institutes Series ((NSSA,volume 7))

Abstract

Most foreign compounds (xenobiotics) are metabolised in vivo producing conjugates (e.g. glucuronldes, sulphates, amino acid conjugates), which are fairly strong organic acids and are readily excreted in either the urine or bile (see Williams and Millburn, 1975). Compounds excreted in the bile may eventually be eliminated in the faeces but prior to this they can undergo an enterohepatic circulation or be metabolised in the intestine by the enzymes of the gut microflora. The latter can carry out a considerable number of reactions on xenobiotics, particularly hydrolytic and reductive reactions, and in certain instances this can lead to the production of toxic metabolites (see Williams 1972). If the excretion of a compound in the bile leads to an enterohepatic circulation this will prolong the presence of the compound or its metabolites in the body. This increases the chances of toxic reactions occurring and may prolong the pharmacological effects of some substances. It is, therefore, important to know the types of xenobiotic compounds excreted in bile and whether this excretory pattern varies with species.

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References

  • Abou-El-Makarem, M. M. (1967). Studies on the Biliary Excretion of Some Foreign Organic Compounds in Different Species. Ph.D. Thesis. University of London.

    Google Scholar 

  • Abou-El-Makarem, M. M., Millbum, P., Smith, R.L. and Williams, R.T. (1967a). Biliary Excretion of Foreign Compounds; Benzene and its Derivatives in the Rat, Biochem. J. 105, 1269–1274.

    CAS  Google Scholar 

  • Abou-El-Makarem, M. M., Millbum, P., Smith R. L. and Williams R.T. (1967b). Biliary Excretion of Foreign Compounds; Species Differences in Biliary Excretion, Biochem. J. 105, 1289–1293.

    CAS  Google Scholar 

  • Abou-El-Makarem, M. M., Millbum, P., and Smith R. L. (1967c) Biliary Excretion of [14C] Succinylsulphathiazole in the Rat and Rabbit, Biochem. J. 105, 1295–1299.

    CAS  Google Scholar 

  • Bertagni, P., Hirom, P. C., Millbum, P., Osiyemi, F. O., Smith,R. L., Turbert, H. B. and Williams, R.T. (1972) Sex and Species Differences in the Biliary Excretion of Tartrazine and Lissamine Fast Yellow in the Rat, Guinea Pig and Rabbit. The influence of Sex Hormones on Tartrazine Excretion in the Rat, J. Pharm. Pharmacol. 24, 620–624.

    Article  PubMed  CAS  Google Scholar 

  • Brauer, R.W. (1959) Mechanisms of Bile Secretion, J. Amer. Med. Ass., 169, 1462–1466.

    Article  CAS  Google Scholar 

  • Bridges, J.W., French, M.R., Smith, R.L. and Williams, R.T. (1970) The Fate of Benzoic Acid in Various Species, Biochem. J. 118, 47–51.

    PubMed  CAS  Google Scholar 

  • Capel, I.D., French, M.R., Millbum, P., Smith, R.L. and Williams R.T. (1972). The Fate of [14C] Phenol in Various Species, Xenobiotica 2, 25–34.

    Article  PubMed  CAS  Google Scholar 

  • Duggan, D.E., Baldwin, J.J., Arisen, B.H. and Rhodes, R.E. (1974) N-Glucoside Formation as a Detoxification Mechanism in Mammals, J. Pharmacol. Exp. Ther. 190, 563–569.

    PubMed  CAS  Google Scholar 

  • Fleischner, G.,Robbins, J., and Arias, L M. (1972) Immunological Studies of Y Protein. A Major Cytoplasmic Organic Anion-Binding Protein in Rat Liver, J. Clin. Invest. 51, 677–684.

    Article  PubMed  CAS  Google Scholar 

  • Gregson, R.H. S., Hirom, P.C., Millburn, P., Smith,R.L., Turbert, H.B. and Williams, R.T. (1972) The Biliary Excretion of Tartrazine. Sex Differences in the Rat and Species Differences in the Rat, Guinea Pig and Rabbit, J. Pharm. Pharmacol 24, 20–24.

    Article  PubMed  CAS  Google Scholar 

  • Gustafson, J.H., and Benet, L. Z. (1974) Biliary Excretion Kinetics of Phenolphthalein glucuronide after intravenous and retrograde biliary administration, J. Pharm. Pharmacol. 26, 937–944.

    Article  PubMed  CAS  Google Scholar 

  • Hirom, P.C. (1970) Factors Influencing the Biliary Excretion of Organic Compounds, Ph.D. Thesis, University of London.

    Google Scholar 

  • Hirom, P. C., Millburn, P., Smith, R. L., and Williams, R.T. (1972a). Species Variations in the Threshold Molecular-Weight Factor for the Biliary Excretion of Organic Anions, Biochem. J. 129, 1071–1077.

    CAS  Google Scholar 

  • Hirom, P.C., Millburn, P., Smith, R.L. and Williams, R.T. (1972b). Molecular Weight and Chemical Structure as Factors in the Biliary Excretion of Sulphonamides in the Rat. Xenobiotica, 2, 205–214.

    Article  CAS  Google Scholar 

  • Hirom, P. C., Hughes, R.D. and Millburn, P. (1974) The Physicochemical Factor Required for the Biliary Excretion of Organic Cations and Anions., Biochem. Soc. Trans. 2, 327–330.

    CAS  Google Scholar 

  • Hughes, R.D., Millburn, P., and Williams, R.T. (1973a). Molecular Weight as a Factor in the Excretion of Monoquatemary Ammonium Cations in the Bile of the Rat, Rabbit and Guinea Pig, Biochem. J. 136, 967–978.

    CAS  Google Scholar 

  • Hughes, R.D., Millburn, P., and Williams, R.T. (1973b) Biliary Excretion of Some Diquaternary Ammonium Cations in the Rat, Guinea Pig and Rabbit Biochem. J. 136, 979–984.

    CAS  Google Scholar 

  • Iga, T., Awazu, S., Hanano, M and Nogami, H., (1970) Pharmacokinetic Studies of Biliary Excretion I. Comparison of the Excretion Behaviour In Azo Dyes and Indigo Carmine, Chem. Pharm. Bull. Tokyo, 18, 2431–2440.

    Article  PubMed  CAS  Google Scholar 

  • Iga, T., Awazu, S., and Nogami, H. (1971) Pharmacokinetic Study of Biliary Excretion II. Comparison of Excretion Behaviour in Triphenylmethane Dyes, Chem. Pharm. Bull., Tokyo, 19, 273–281.

    Article  CAS  Google Scholar 

  • Levi, A.J., Gatmaitan, Z. and Arias, I.M. (1969) 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.

    Article  PubMed  CAS  Google Scholar 

  • Levine, W. G., Millbum, P., Smith, R.L. and Williams, R.T. (1970) 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.

    Article  PubMed  CAS  Google Scholar 

  • Litwack, G., Ketterer, B., and Arias, I.M. (1971) Ligandin : A Hepatic Protein which binds Steroids, Bilirubin, Carcinogens and a Number of Exogenous Organic Anions, Nature, Lond., 234, 466–467.

    Article  CAS  Google Scholar 

  • Millburn, P. (1970) Factors in the Biliary Excretion of Organic Compounds In Metabolic Conjugation and Metabolic Hydrolysis (Fishman, W. H., ed.) Vol. 2, pp. 1–74, Academic Press, London.

    Chapter  Google Scholar 

  • Millburn, P., Smith, R.L. and Williams, R.T. (1967) 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.

    PubMed  CAS  Google Scholar 

  • Peterson, R.E. and Fujimoto, J.M. (1973) Retrograde Intrabiliary Injection: Absorption of Water and Other Compounds from the Rat Biliary Tree, J. Pharmacol. Exp. Ther. 185, 150–162.

    PubMed  CAS  Google Scholar 

  • Schanker, L. S. and Solomon, H. M. (1963). Active Transport of Quatemary Ammonium Compounds into Bile. Amer.J. Physiol. 204, 829–832.

    PubMed  CAS  Google Scholar 

  • Smith, R. L. (1974) Biliary Excretion and Hepatotoxicity of Contraceptive Steroids. Acta Endocr., Copenh. 75, Suppl. 185, pp. 149–168.

    CAS  Google Scholar 

  • Ryrfeldt, A. (1971) Biliary Excretion of Penicillins in the Rat, J. Pharm. Pharmacol., 23, 463–464.

    Article  PubMed  CAS  Google Scholar 

  • Smith, R.L. (1973) The Excretory Function of Bile. Chapman and Hall, London.

    Google Scholar 

  • Sperber, L, (1963) Biliary Excretion and Choleresis. In Proceedings of the First International Pharmacological Meeting, August 22–25, 1961, Vol. 4, Drugs and Membranes. (Hogben, C.A.M., ed) pp. 137–143, Pergamon Press Ltd., London.

    Google Scholar 

  • Takada,K., Ueda, M., Ohno, M. and Muranishi, S. (1974) Biopharmaceutical Study of the Hepato-Biliary Transport of Drugs II. Roles of the Liver Cytoplasmic Y and Z Binding Proteins and T Binder on the Hepato-Biliary Transport of Organic Anionic Compounds. Chem. Pharm. Bull., Tokyo, 22, 1477–1486.

    Article  CAS  Google Scholar 

  • Taylor, W. (1971) The Excretion of Steroid Hormone Metabolites in Bile and Faeces, Vitam. Horm. (New York) 29, 201–285.

    Article  CAS  Google Scholar 

  • Vainio, H. (1973a) Action of Chaotropic Agents on Drug-Metabolizing Enzymes in Hepatic Microsomes, Biochim. Biophys. Acta, 307, 152–161.

    Article  CAS  Google Scholar 

  • Vainio, H. (1973 b) On the Topology and Synthesis of Drug-Metabolizing Enzymes inHepatic Endoplasmic Reticulum, M. D. Thesis, University of Turku, Finland.

    Google Scholar 

  • Vainio, H. and Hanninen, O. (1972) Effect of Surfactants on Drug Metabolism in Hepatic Microsomes, Suomen Kemistilehti (Finn. Chem. J.) B 45, 56–61.

    Google Scholar 

  • Williams, R.T. (1947) Detoxication Mechanisms, Chapman and Hall, London

    Google Scholar 

  • Williams, R.T. (1972) Toxicologic Implications of Biotransformation by Intestinal Microflora. Toxicol. Appl. Pharmacol. 23, 769–781.

    Article  PubMed  CAS  Google Scholar 

  • Williams, R.T. and Millburn, P. (1975) Detoxication Mechanisms; The Biochemistry of Foreign Compounds, in MTP International Review of Science. Biochemistry Series One. Vol. 12. Physiological and Pharmacological Biochemistry. (Blaschko, H. K. F., ed) pp. 211–266, Butterworths, London.

    Google Scholar 

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Authors and Affiliations

  1. Department of Biochemistry, St. Mary’s Hospital Medical School, London W2, UK

    Peter Millburn

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  1. Peter Millburn
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Editors and Affiliations

  1. The Medical School, The University, Newcastle upon Tyne, England

    W. Taylor

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© 1976 Springer Science+Business Media New York

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Millburn, P. (1976). Excretion of Xenobiotic Compounds in Bile. In: Taylor, W. (eds) The Hepatobiliary System. NATO Advanced Study Institutes Series, vol 7. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-8900-6_7

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  • DOI: https://doi.org/10.1007/978-1-4615-8900-6_7

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4615-8902-0

  • Online ISBN: 978-1-4615-8900-6

  • eBook Packages: Springer Book Archive

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