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Excretion of Drugs in Bile

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Concepts in Biochemical Pharmacology

Abstract

Drugs and other environmental chemicals and their metabolic transformation products are usually eliminated from the body by excretion in the urine or bile or sometimes both. Rarely, depending upon the substance, other pathways may be used such as the expired air, sweat, saliva or milk. The role of the bile in the excretion of products of intermediary metabolism (e.g. the bile salts, bilirubin, steroid and thyroid hormones) has long been known. Recent studies suggest that this role may be greater than hitherto appreciated, since cyanocobalamin, vitamin D, a-tocopherol and porphyrins and their metabolites have also been shown to be extensively excreted in bile. Similarly the role of bile in the excretion of foreign chemicals has only in recent years become more widely recognized. Thus, bile can be important in the elimination of naturally occurring substances such as chlorophyll which normally enters the body via the diet as well as many of the synthetic organic compounds encountered such as drugs, food additives and pesticides.

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References

  • Abel, J. J., Rowntree, L.G.: On the pharmacological action of some phthaleins and their derivatives, with especial reference to their behavior as purgatives. J. Pharm. Pharmacol. 1, 231–264 (1909).

    Google Scholar 

  • Abou-El-Makarem, M.M., Millburn, P., Smith, R.L., Williams, R.T.: Biliary excretion of foreign compounds: Benzene and its derivatives in the rat. Biochem. J. 105, 1269–1274 (1967a).

    PubMed  CAS  Google Scholar 

  • Abou-El-Makarem, M.M., Millburn, P., Smith, R.L., Williams, R.T., Biliary excretion of foreign compounds: Species differences in biliary excretion. Biochem. J. 105, 1289–1293 (1967b).

    PubMed  CAS  Google Scholar 

  • Abou-El-Makarem, M.M., Millburn, P., Smith, R.L., Williams, R.T., Unpublished observations (1967c).

    Google Scholar 

  • Adamson, R.H., Bridges, J.W., Evans, M.E., Williams, R.T.: Species differences in the aromatization of quinic acid in vivo and the role of gut bacteria. Biochem. J. 116, 437–443 (1970).

    PubMed  CAS  Google Scholar 

  • Baker, K.J., Bradley, S.E.: Binding of sulfobromophthalein (BSP) sodium by plasma albumin. Its role in hepatic BSP extraction. J. clin. Invest. 45, 281–287 (1966).

    Article  PubMed  CAS  Google Scholar 

  • Beckett, A.H., Rowland, M.: Urinary excretion kinetics of amphetamine in man. J. Pharm. Pharmacol. 17, 628–639 (1965).

    Article  PubMed  CAS  Google Scholar 

  • Bettman, R., Spier, E.: Concentration of sulfanilamide in human bile. Proc. Soc. exp. Biol. (N.Y.) 41, 463–464 (1939).

    CAS  Google Scholar 

  • Borgström, B., Dahlqyist, A., Lundh, G., Sjovall, J.: Studies of intestinal digestion and absorption in the human. J. clin. Invest. 36, 1521–1536 (1957).

    Article  PubMed  Google Scholar 

  • Boyland, E., Ramsay, G.S., Sims, P.: Metabolism of polycyclic compounds: The secretion of metabolites of naphthalene, 1:2-dihydronaphthalene and l:2-epoxy-1:2:3:4-tetra- hydronaphthalene in rat bile. Biochem. J. 78, 376–384 (1961).

    PubMed  CAS  Google Scholar 

  • Brauer, R.W.: Mechanisms of bile secretion. J. Amer. med. Ass. 169, 1462–1466 (1959).

    CAS  Google Scholar 

  • Brauer, R.W., Pessotti, R.L.: Hepatic uptake and biliary excretion of bromsulphthalein in the dog. Amer. J. Physiol. 162, 565–574 (1950).

    PubMed  CAS  Google Scholar 

  • Burns, E.C., Dahm, P. A., Lindquist, D.A.: Secretion of DDT metabolites in the bile of rats. J. Pharmacol, exp. Ther. 121, 55 — 62 (1957).

    CAS  Google Scholar 

  • Caesar, J., Shaldon, S., Chiandussi, L., Guevara, L., Sherlock, S.: The use of indo- cyanine green in the measurement of hepatic blood flow and as a test of hepatic function. Clin. Sci. 21, 43–57 (1961).

    PubMed  CAS  Google Scholar 

  • Calvey, T.N.: The biliary excretion of neostigmine in the rat. Brit. J. Pharmacol. 28, 348 to 359 (1966).

    Google Scholar 

  • Cantarow, A., Wirts, C.W., Snape, W.J., Miller, L.L.: Excretion of bilirubin and brom-sulfalein in bile. Amer. J. Physiol. 154, 211 — 219 (1948).

    PubMed  CAS  Google Scholar 

  • Cherrick, G.R., Stein, S.W.,Leevy, C.M., Davidson, C.S.: Indocyanine green: Observations on its physical properties, plasma decay and hepatic extraction. J. clin. Invest. 39, 592 — 600 (1960).

    CAS  Google Scholar 

  • Chrzonszczewsky, N.: Zur Anatomie und Physiologie der Leber. Arch. Path. Anat. und Physiol. 35, 153 — 165 (1866).

    Article  Google Scholar 

  • Clark, A.G., Fischer, L.J., Millburn, P., Smith, R.L., Williams, R.T.: Unpublished observations (1970).

    Google Scholar 

  • Clark, A.G., Fischer, L.J., Millburn, P., Smith, R.L., Williams, R.T., The role of gut flora in the enterohepatic circulation of stilboestrol in the rat. Biochem. J. 112, 17P (1969b).

    Google Scholar 

  • Clark, A.G., Fischer, L.J., Hirom, P.C., Millburn, P., Smith, R.L., Williams, R.T.: Reabsorption from the biliary system as a factor influencing the biliary excretion of organic anions. Biochem. J. 11, 5 62P (1969a).

    Google Scholar 

  • Combes, B., Stakelum, G.S.: Conjugation of sulfobromophthalein sodium with glutathione in thioether linkage by the rat. J. clin. Invest. 39, 1214–1222 (1960).

    Article  PubMed  CAS  Google Scholar 

  • Cox, E., WRIGHT, S.E.: The hepatic excretion of digitalis glycosides and their genins in the rat. J. Pharmacol, exp. Ther. 126, 117–122 (1959).

    CAS  Google Scholar 

  • Czok, G., Hirom, P., Millburn, P., Smith, R.L., Williams, R.T.: Unpublished observations (1970).

    Google Scholar 

  • Daniel, J.W., Gage, J.C.: Absorption and excretion of diquat and paraquat in rats. Brit. J. industr. Med. 23, 133–136 (1966).

    PubMed  CAS  Google Scholar 

  • Davidson, J.D.: The influence of enterohepatic circulation on toxicity of drugs, paper discussed by Williams, R.T., Millburn, P. and Smith, R.L. Ann. N.Y. Acad. Sci. 123, 110–124 (1965).

    Google Scholar 

  • Davison, C., Williams, R.T.: The metabolism of 5,5’-methylenedisalicylic acid in various species. J. Pharm. Pharmacol. 20, 12–18 (1968).

    Article  PubMed  CAS  Google Scholar 

  • Delaney, V.G., Millburn, P., Smith, R.L.: Unpublished observations (1969).

    Google Scholar 

  • Elliott, H.W., Tolbert, B.M., Adler, T.K., Anderson, H.H.: Excretion of carbon-14by man after administration of morphine-N-methyl-C14. Proc. Soc. exp. Biol. (N.Y.) 85, 77–81 (1954).

    CAS  Google Scholar 

  • Farah, A.: On the elimination of G-strophanthin by the rat. J. Pharmacol, exp. Ther. 86, 248–257 (1946).

    CAS  Google Scholar 

  • Fischer, L.J., Millburn, P.: J. Pharmacol, exp. Ther. (in press) (1970).

    Google Scholar 

  • Fischer, L.J., Millburn, P., Smith, R.L., Williams, R.T.: The fate of [14C] stilboestrol in the rat. Biochem. J. 100, 69P (1966).

    Google Scholar 

  • Furesz, S., Scotti, R.: Rifomycin: XX-Further studies on rifomycin SV: in vitro activity, absorption and elimination in man. Farmaco, Ed. sci. 16, 262–271 (1961).

    Google Scholar 

  • Glazko, A. J., Dill, W.A., Wolf, L.M.: Observations on the metabolic disposition of chloramphenicol (Chloromycetin) in the rat. J. Pharmacol, exp. Ther. 104, 452–458 (1952).

    CAS  Google Scholar 

  • Graham, E.A., Cole, W.H., Copher, G.H., Moore, S.: In: “Diseases of the gallbladder and Bile Ducts”. Philadelphia: Lea & Febiger 1928.

    Google Scholar 

  • Griffith, R.S., Johnstone, D.M., Smith, J.W.: In: “Antibiotics Annual”, p. 496. H. Welch and F. Marti-Ibanez, Eds. Medical Encyclopedia Inc. N.Y. (1953/1954).

    Google Scholar 

  • Gross, M., Greenberg, L.A.: In: “The Salicylates”, p. 49. New Haven: Hillhouse Press 1948.

    Google Scholar 

  • Hargreaves, T., Lathe, G.H.: In: “Therapeutic Agents and the Liver”, p. 9. N. McIntyre and S. Sherlock, Eds. Oxford: Blackwell 1965.

    Google Scholar 

  • Hart, L.G., Guarino, A.M., Adamson, R.H.: Effects of phenobarbital on biliary excretion of organic acids in male and female rats. Amer. J. Physiol. 217, 46–52 (1969).

    PubMed  CAS  Google Scholar 

  • Hearse, D.J., Powell, G.M., Olavesen, A.H., Dodgson, K.S.: The influence of some physic-chemical factors on the biliary excretion of a series of structurally related aryl sulphate esters. Biochem. Pharmacol. 18, 181–195 (1969).

    Article  PubMed  CAS  Google Scholar 

  • Hirom, P.C., Millburn, P., Smith, R.L., Williams, R.T.: Studies on the relationship between molecular structure and the biliary excretion of organic compounds. Biochem. J. 113, 27–28P (1969).

    Google Scholar 

  • Hucker, H.B., Zacchei, A.G., Cox, S.V., Brodie, D.A., Cantwell, N.H.R.: Studies on the absorption, distribution and excretion of indomethacin in various species. J. Pharmacol. exp. Ther. 153, 237–249 (1966).

    CAS  Google Scholar 

  • Inscoe, J.K., Axelrod, J.: Some factors affecting glucuronide formation in vitro, J. Pharmacol. exp. Ther. 129, 128–131 (1960).

    PubMed  CAS  Google Scholar 

  • Javitt, N.B.: In: “Therapeutic Agents and the Liver”, p. 17. N. McIntyre and S.Sherlock Eds. Oxford: Blackwell 1965.

    Google Scholar 

  • Javitt, N.B., Wheeler, H.O., Baker, K.J., Ramos, O.L., Bradley, S.E.: The intrahepatic conjugation of sulfobromophthalein and glutathione in the dog. J. clin. Invest. 39, 1570–1577 (1960).

    Article  PubMed  CAS  Google Scholar 

  • Jirsa, M., Dickinson, J.P., Lathe, G.H.: Effect on bilirubin excretion of blocking the carboxyl sites of glucuronide conjugation by methylation. Nature (Lond.) 220, 1322–1234 (1968).

    Article  CAS  Google Scholar 

  • Keberle, H., Hoffmann, K., Bernhard, K.: The metabolism of glutethimide (Doriden). Experientia (Basel) 18, 105–110 (1962).

    Article  CAS  Google Scholar 

  • Kellie, A.E., Smith, E.R.: Renal clearance of 17-oxo steroid conjugates found in human peripheral plasma. Biochem. J. 66, 490–495 (1957).

    PubMed  CAS  Google Scholar 

  • Krebs, J. S.: Relation of the metabolism of sulfobromophthalein sodium to its blood clearance in the rat. Amer. J. Physiol. 197, 292–296 (1959).

    PubMed  CAS  Google Scholar 

  • Krebs, J. S., Bratter, R.W.: Metabolism of sulfobromophthalein sodium (BSP) in the rat. Amer. J. Physiol. 194, 37–43 (1958).

    PubMed  CAS  Google Scholar 

  • Levi, A. J., Gatmaitan, Z., Arias, I.M.: Two cytoplasmic proteins from rat liver and their role in hepatic uptake of sulfobromophthalein (BSP) and bilirubin. J. clin. Invest. 47, 61a (1968).

    Google Scholar 

  • Levine, R.M., Clark, B.B.: The biotransformation, excretion, and distribution of the anticholinergic quaternary ammonium compound benzomethamine [N-diethylamino-ethyl-N’-methyl-benzilamide methobromide (MC 3199)] and its tertiary amine analogue (MC 3137) and related compounds in animals. J. Pharmacol, exp. Ther. 114, 63–77 (1955).

    CAS  Google Scholar 

  • Levine, R.M., Clark, B.B.: The physiological disposition of oxyphenonium bromide (antrenyl) and related compounds. J. Pharmacol, exp. Ther. 121, 63–70 (1957).

    CAS  Google Scholar 

  • Levine, R. R.: The physiological disposition of hexamethonium and related compounds. J. Pharmacol, exp. Ther. 129, 296–304 (1960).

    CAS  Google Scholar 

  • Levine, W.G., Millburn, P., Smith, R.L., Williams, R.T.: The role of the hepatic endo-plasmic reticulum in the biliary excretion of foreign compounds by the rat. Biochem. Pharmacol. 19, 235–244 (1970).

    Article  PubMed  CAS  Google Scholar 

  • Levitz, M., Katz, J.: Enterohepatic metabolism of estriol-3-sulfate-16-glucosiduronate in women. J. clin. Endocr. 28, 862–868 (1968).

    Article  PubMed  CAS  Google Scholar 

  • Linnecar, D.F.: Personal communication (1970).

    Google Scholar 

  • Maffii, G., Bianchi, G., Schiatti, P., Gallo, G.G.: Rifomycin: XIX Absorption, biliary excretion and distribution of rifomycin SV. Farmaco, Ed. sci. 16, 246–261 (1961).

    CAS  Google Scholar 

  • March, C.H., Elliott, H. W.: Distribution and excretion of radioactivity after administration of morphine-N-methyl C14 to rats. Proc. Soc. exp. Biol. (N.Y.) 86, 494 - 497 (1954).

    CAS  Google Scholar 

  • De Marco, J., Levine, R.R.: Role of the lymphatics in the intestinal absorption and distribution of drugs. J. Pharmacol, exp. Ther. 169, 142–151 (1969).

    Google Scholar 

  • Mellett, L.B., Woods, L.A.: The distribution and fate of morphine in the non-tolerant and tolerant monkey. J. Pharmacol, exp. Ther. 116, 77–83 (1956).

    CAS  Google Scholar 

  • Meltzer, J.I., Wheeler, H.O., Cranston, W.I.: Metabolism of sulfobromophthalein sodium (BSP) in dog and man. Proc. Soc. exp. Biol. (N.Y.) 100, 174–179 (1959).

    CAS  Google Scholar 

  • Meurman, L.: On the distribution and kinetics of injected I131 rose bengal. Chapter IX, Behavior of I131 rose bengal in bile-duct obstructed animals. Acta med. scand. Suppl. 354, 60–67 (1960).

    Google Scholar 

  • Michel, W. R.: Metabolism of linear alkylate sulfonate and alkyl benzene sulfonate in albino rats. Toxicol, appl. Pharmacol. 12, 473–485 (1968).

    Google Scholar 

  • Millburn, P., Smith, R.L.: Unpublished observations (1970).

    Google Scholar 

  • Millburn, P., Smith, R.L., Williams, R.T.: 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).

    PubMed  CAS  Google Scholar 

  • Monroe, L.S., Kittinger, A.L.: The biliary dynamics of the metabolites of sulfobromophthalein sodium (BSP) in man. J. Lab. clin. Med. 58, 468–476 (1961).

    PubMed  CAS  Google Scholar 

  • Mosler, F.: Untersuchungen über den Übergang von Stoffen aus dem Blute in die Galle. Arch. Pathol. Anat. und Physiol. 13, 29–46 (1858).

    Article  Google Scholar 

  • Moss, G.: Personal communication (1970).

    Google Scholar 

  • Norman, A., Sjövall, J.: On the transformation and enterohepatic circulation of cholic acid in the rat. J. biol. Chem. 233, 872–885 (1958).

    PubMed  CAS  Google Scholar 

  • Nosslin, B., Morgan, E.H.: The effect of phloroglucinol derivatives from male fern on dye excretion by the liver in the rabbit and rat. J. Lab. clin. Med. 65, 891–902 (1965).

    PubMed  CAS  Google Scholar 

  • Okita, G.T., Talso, P.J., Curry, J.H., Jr., Smith, F.D., Jr., Geiling, E.M.K.: Metabolic fate of radioactive digitoxin in human subjects. J. Pharmacol, exp. Ther. 115, 371–379 (1955).

    CAS  Google Scholar 

  • Oliverio, V.T., Davidson, J.D.: The physiological disposition of dichloromethotrexate-Cl in animals. J. Pharmacol, exp. Ther. 137, 76–83 (1962).

    CAS  Google Scholar 

  • Parke, D.V., Williams, R.T.: Species differences in the o- and p-hydroxylation of aniline. Biochem. J. 63, 12P (1956).

    Google Scholar 

  • Pinto, J.D., Camien, M.N., Dunn, M.S.: Metabolic fate of p,p’-DDT [l,l,l-trichloro-2,2-bis (p-chlorophenyl) ethane] in rats. J. biol. Chem. 240, 2148–2154 (1965).

    PubMed  CAS  Google Scholar 

  • Radomski, J.L., Melunger, T. J.: The absorption, fate and excretion in rats of the water-soluble azo dyes, FD & C red No. 2, FD & C red No. 4, and FD & C yellow No. 6. J. Pharmacol, exp. Ther. 136, 259–266 (1962).

    CAS  Google Scholar 

  • Robinson, D., Williams, R.T.: Do cats form glucuronides ? Biochem. J. 68, 23P–24P (1958).

    CAS  Google Scholar 

  • Rosenthal, S.M., White, E.C.: Clinical application of the bromsulphalein test for hepatic function. J. Amer. med. Ass. 84, 1112–1114 (1925).

    Google Scholar 

  • Ryan, A. J., Wright, S.E.: Biliary excretion of some azo dyes related to tartrazine. Nature (Lond.) 195, 1009 (1962).

    Article  CAS  Google Scholar 

  • Sandberg, A.A., Slaunwhite, W.R., Jr.: Biliary excretion and protein binding of radio-active steroids in human subjects: their possible relationship. J. clin. Endocr. 16, 923–924 (1956).

    Article  Google Scholar 

  • Schanker, L.S.: In: “Proceedings of the First International Pharmacological Meeting”, Vol. 4, p. 121. New York: Pergamon Press 1963.

    Google Scholar 

  • Schanker, L.S.: In: “Handbook of Physiology” Section 6: Alimentary Canal, Vol. 5, Chapter 114, p. 2433. American Physiological Society, Washington, D. C., 1968.

    Google Scholar 

  • Scheline, R.R.: Drug metabolism by intestinal microorganisms. J. pharm. Sci. 57, 2021 to 2037 (1968).

    Google Scholar 

  • Schenker, S., Goldstein, J., Combes, B.: Sulfobromophthalein sodium (BSP) conjugation and excretion in fetal guinea pigs. Amer. J. Physiol. 208, 563–572 (1965).

    PubMed  CAS  Google Scholar 

  • Smith, R.L.: Fortschritte der Arzneimittelforschung. H. Jucker, Ed. Progr. Drug. Res. 9, 299 (1966).

    CAS  Google Scholar 

  • Smith, R.L.: Proceedings European Society for the Study of Drug Toxicity 11, 19 (1970).

    Google Scholar 

  • Smith, R.L., Williams, R.T.: In: “Glucuronic Acid”. G.J. Dutton, Ed. New York: Academic Press 1966.

    Google Scholar 

  • Sobotka, H.: In: “Physiological Chemistry of the Bile”, pp. 100–101. London: Balliere, Tindall and Cox 1937.

    Google Scholar 

  • Sperber, I.: The excretion of some glucuronic acid derivatives and phenol sulphuric esters in the chicken. K. Lantbr. Högsk. Annlr. 15, 317–349 (1948).

    CAS  Google Scholar 

  • Sperber, I.: Secretion of organic anions in the formation of urine and bile. Pharmacol. Rev. 11, 109 to 134 (1959).

    Google Scholar 

  • Sperber, I.: Proceedings of the First International Pharmacological Meeting, Vol. 4, p. 137. C.A.M. Hogden, Ed. New York: Macmillan 1963.

    Google Scholar 

  • Thompson, R., Sturtevant, M., Bird, O.D., Glazko, A.J.: The effect of metabolites of chloramphenicol (Chloromycetin) on the thyroid of the rat. Endocrinology 55, 665–681 (1954).

    Article  PubMed  CAS  Google Scholar 

  • Weiner, I.M., Mudge, G.H.: Renal tubular mechanisms for excretion of organic acids and bases. Amer. J. Med. 36, 743–762 (1964).

    Article  PubMed  CAS  Google Scholar 

  • Weisburger, J.H., Hadidian, Z., Fredrickson, T.N., Weisburger, E.K.: Host properties determine target, bladder or liver in chemical carcinogenesis. In: “Bladder Cancer” Aesculapius Publ. Co., Florida (1967).

    Google Scholar 

  • Weithaler, K., Wilfeingseder, P., Friza, F.: Zur Frage der Ausscheidung von Tetra-cyclin in die Galle. Klin. Wschr. 35, 297–300 (1957).

    Article  PubMed  CAS  Google Scholar 

  • Wheeler, H.O., Cranston, W.I., Meltzer, J.I.: Hepatic uptake and biliary excretion of indocyanine green in the dog. Proc. Soc. exp. Biol. (N.Y.) 99, 11–14 (1958).

    CAS  Google Scholar 

  • Williams, R. T.: Comparative patterns of drug metabolism. Fed. Proc. 26, 1026–1039 (1967).

    Google Scholar 

  • Williams, R. T., Mellburn, P., Smith, R.L.: The influence of enterohepatic circulation on toxicity of drugs. Ann. N.Y. Acad. Sci. 123, 110–124 (1965).

    Article  PubMed  CAS  Google Scholar 

  • Woods, L.A.: Distribution and fate of morphine in non-tolerant and tolerant dogs and rats. J. Pharmacol, exp. Ther. 112, 158–175 (1954).

    CAS  Google Scholar 

  • Zaslow, J., Cohen, E.M., Ball, W.: In: “Antibiotics Annual”, p. 964. H. Welch and F. Marti-Ibanez, Eds. New York: Medical Encyclopedia Inc. 1955.

    Google Scholar 

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Smith, R.L. (1971). Excretion of Drugs in Bile. In: Brodie, B.B., Gillette, J.R., Ackerman, H.S. (eds) Concepts in Biochemical Pharmacology. Handbuch der experimentellen Pharmakologie/Handbook of Experimental Pharmacology, vol 28 / 1. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-65052-9_19

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