Skip to main content

Advertisement

SpringerLink
Log in

Pharmacology of bile acids and their derivatives: Absorption promoters and therapeutic agents

  • Published:
European Journal of Drug Metabolism and Pharmacokinetics Aims and scope Submit manuscript

Summary

The role of bile acids in pharmacotherapy is reviewed in this article. The therapeutic use of bile has been recognized since ancient times. Previously bile acids were the standard treatment for gallstones where chenodeoxycholic acid and ursodeoxycholic acid were effective in promoting the dissolution of cholesterol gallstones. Today their therapeutic role looks set to expand enormously. Bile acids as absorption promoters have the potential to aid intestinal, buccal, transdermal, ocular, nasal, rectal and pulmonary absorption of various drugs at concentrations that are non-toxic. Keto derivatives of cholic acid, such as 3a, 7a, dihydroxy-12-keto-5a-cholic acid (sodium salt and methyl ester) are potential modifiers of blood-brain barrier transport and have been shown to promote quinine up-take, enhance the analgesic effect of morphine and prolong the sleeping time induced by pentobarbital. They have also been shown to be hypoglycaemic. Bile acids as therapeutic agents have the potential to produce beneficial effects in sexually transmitted diseases, primary biliary cirrhosis, primary sclerosing cholangitis, gallstones, digestive tract diseases, cystic fibrosis, cancer and diabetes.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Laurence D. (ed.) (1998):A Dictionary of Pharmacology and Allied Topics. 2nd edition, Elsevier, The Netherlands.

    Google Scholar 

  2. Hsieh D. (ed.) (1994):Drug Permeation Enhancement Theory and Applications. Marcel Dekker Inc, New York.

    Google Scholar 

  3. Sayani A.P., Chien Y.W. (1996):Critical Reviews in Therapeu tic Drug Carrier Systems 13, 85.

    CAS  Google Scholar 

  4. Trauner M., Boyer J. (2003):Physiol. Rev. 83, 633.

    PubMed  CAS  Google Scholar 

  5. O’Reilly J., Corrigan O., O’Driscoll C. (1994):Int. J. Pharm. 109, 147.

    Article  Google Scholar 

  6. Mesiha M., Ponnapula S., Plakogiannis F. (2002):Int. J. Pharm. 249, 1.

    Article  PubMed  CAS  Google Scholar 

  7. Michael S., Thole M., Dillmann R., Fahr A., Drewe J., Fricker G. (2000):Eur. J. Pharm. Sci. 10, 133.

    Article  PubMed  CAS  Google Scholar 

  8. Mrestani Y., Bretschneider B., Harti A., Neubert R. (2003):J. Pharm. Pharmacol. 55, 1601.

    Article  PubMed  CAS  Google Scholar 

  9. Newton J.M., Rowley G., Tornblom J.V. (1971):J. Pharm. Pharmacol. 23, 156S.

    PubMed  CAS  Google Scholar 

  10. Borras-Blasco J., Diez-Sales O., Lopez A., Herraez-Dominguez M. (2004):Int. J. Pharm., 269.

  11. Hye J.A., Kyoung M.K., Kim C.-K. (1998):Drug Devel. Indust. Pharm. 24, 697.

    Article  Google Scholar 

  12. Martin-Algarra R.V., Pascual-Costa R.M., Merino M., Casabo V.G. (1994):Pharm. Res. 11, 1042.

    Article  PubMed  CAS  Google Scholar 

  13. Senel S., Hoogstraate F., Spies J.C., Verhoef H.E., Junginger H.E., Bodde H.E. (1993):Eur. J. Morphol. 31, 35.

    PubMed  CAS  Google Scholar 

  14. Nakane S., Kakumoto M., Yukimatsu K., Chien Y.W. (1996):Pharmac. Devel. Technol. 1, 251.

    Article  CAS  Google Scholar 

  15. Deneer V., Drese G., Roemele P., Verhoef J., Lie-A-Huen L., Kingma J., Brouwers J., Junginger H. (2002):Int. J. Pharm. 241, 127.

    Article  PubMed  CAS  Google Scholar 

  16. Gandhi R., Robinson J.R. (1985):Int. J. Pharmacol. 85, 129.

    Article  Google Scholar 

  17. Lee V.H.L., Yamamoto A., Kompella U.B. (1991):Crit. Rev. Ther. Drug Carrier Systems 8, 91.

    CAS  Google Scholar 

  18. Hofer C., Härtung R., Göbel R., Deering P., Lehmer A., Breul J. (2000):World J. Surg. 24, 1187.

    Article  PubMed  CAS  Google Scholar 

  19. Cevc G., Blume G., Schatzlein A., Gebauer D., Paul A. (1996):Advanced Drug Delivery Systems 18, 349.

    Article  CAS  Google Scholar 

  20. Paul A., Cevc G. (1995):Vaccine Res. 4, 145.

    CAS  Google Scholar 

  21. Guo J., Ping Q., Huang L.J. (1999):China Pharm. Unv. 30, 184–186.

    Google Scholar 

  22. Cevc G., Blume G. (1992):Biochem. Biophys. Acta 1104, 226.

    Article  PubMed  CAS  Google Scholar 

  23. Nokhodchi A., Shokri J., Dashbolaghi A., Hassan-Zadeh D., Ghafourian T., Barzegar-Jalali M. (2003):Int. J. Pharm. 250, 359.

    Article  PubMed  CAS  Google Scholar 

  24. Shokri J., Nokhodchi A., Dashbolaghi A., Hassan-Zadeh D., Ghafourian T., Barzegar-Jalali M. (2001):Int. J. Pharm. 228, 99.

    Article  PubMed  CAS  Google Scholar 

  25. Yamamoto A., Luo A., Dodda-Kashi S., Lee V. (1989):J. Pharmacol. Exp. Ther. 249, 249.

    PubMed  CAS  Google Scholar 

  26. Longenecker J., Moses A., Flier J., Silver R., Carey M., Dubovi (1987):J. Pharm. Sci. 76, 351.

    Article  PubMed  CAS  Google Scholar 

  27. Samiy N., D’Amico D.J. (1996):Int. Ophthalmol. Clin. 36, 147.

    Article  PubMed  CAS  Google Scholar 

  28. Tabbara K.F., Hyndiuk R.A. (eds) (1996):Infections of the Eye. 2nd Edition, Little, Brown, Boston.

    Google Scholar 

  29. Souri E.N., Green W.R. (1974):Am. J. Ophthalmol. 78, 77.

    PubMed  CAS  Google Scholar 

  30. Doft B.H., Weiskopf J., Nilsson-Ehle I., Wingard L.B. (1985):Ophthalmology 92, 1601.

    PubMed  CAS  Google Scholar 

  31. Tremblay C., Barza M., Szoka F., Lahav M., Baum J. (1985):Invest. Ophthalmol. Vis. Sci. 26, 711.

    PubMed  CAS  Google Scholar 

  32. Cannon J.P., Hscella R., Pattharachayakul S., Garey K.W., De Alba F., Piscitelli S., Edward D.P., Danziger L.H. (2003):Invest. Ophthalmol. Vis. Sci. 44, 2112.

    Article  PubMed  Google Scholar 

  33. Shao Z., Mitra A.K. (1992):Pharm. Res. 9, 1184.

    Article  PubMed  CAS  Google Scholar 

  34. Gordon G.S., Moses A.C., Silver R.D., Flier J.S., Carey M.C. (1985):Proc. Natl. Acad. Sci. 82, 7419.

    Article  PubMed  CAS  Google Scholar 

  35. Junginger H.E. (1992):Drug Targeting and Delivery: Concepts in dosage form design. Ellis Horwood Limited, England.

    Google Scholar 

  36. Hersey S.J, Jackson R.T. (1987):J. Pharm. Sci. 76, 877.

    Google Scholar 

  37. Ilium L., Fischer A.N., Jabbal-Gill I., Davis S.S. (2001):Int. J. Pharm. 222, 109.

    Article  Google Scholar 

  38. Bjork E., Bjurstron S., Edman P. (1991):Int. J. Pharm. 75, 73.

    Article  Google Scholar 

  39. Hirai S., Ikenaga T., Matsuzawa T. (1978):Diabetes 27, 296.

    Article  CAS  Google Scholar 

  40. Moses A.C., Gordon G.S., Carey M.C., Flier J.S. (1983):Diabetes 32, 1041.

    Article  Google Scholar 

  41. Alberts B., Bray D., Lewis J., Raff M., Roberts K., Watson J. (eds) (1983):Molecular Biology of the Cell. Garland, New York.

    Google Scholar 

  42. Donovan M.D., Flynn G.L., Amidon G.L. (1990):Pharm Res., 7, 808.

    Article  PubMed  CAS  Google Scholar 

  43. Aungst B.J., Rogers N.J., Shefter E. (1988):J. Pharmacol. Exp. Ther. 244, 23.

    PubMed  CAS  Google Scholar 

  44. Agu R.U., Ugwoke M.I., Armand M., Kinget R., Verbeke N. (2001):Respir. Res. 2, 198.

    Article  PubMed  CAS  Google Scholar 

  45. Heinemann L., KIoppoth W., Rave K., Hompesch B., Linkeschowa R., Heise T. (2000):Diabetes Care, 23, 1343.

    Article  PubMed  CAS  Google Scholar 

  46. Fukuda Y., Tsuji T., Fujita T., Yamamoto A., Muranishi S. (1995):Biol. Pharm. Bull. 18, 891.

    PubMed  CAS  Google Scholar 

  47. Widmaier E., Raff H., Strang K. (eds) (2004):Vander, Sherman and Luciano’s Human Physiology — The Mechanisms of Body Function. 9th Edition, McGraw-Hill, Boston.

    Google Scholar 

  48. Yamamoto A., Okumura S., Fukuda Y., Fukui M., Takahashi K., Muranishi S. (1997):J. Pharm. Sci. 86, 1144.

    Article  PubMed  CAS  Google Scholar 

  49. Monta T., Yamamoto A., Takakura Y., Hashida M., Sezaki H. (1994):Pharm. Res. 11, 909.

    Article  Google Scholar 

  50. Kaneko T., Sato T., Katsuya H., Miyauchi Y. (1990):Crit. Care Med. 18, 77, 1990.

    Article  PubMed  CAS  Google Scholar 

  51. Watanaube A., Fujuwara M., S. Tominaga, Nagashima H. (1987):Hiroshima J. Med. Sci. 36, 257.

    Google Scholar 

  52. Spiegelman M.K., Zappulla R.A., Malis L.I., Holland J.F., Goldsmith S.J., Goldberg J.D. (1983):Neurosurgery 12, 606.

    Article  Google Scholar 

  53. Mikov M., Kevresan S., Kuhajda K., Jakovljevic V., Vasovic V. (2004):Polish J. Pharmacol. 56, 367.

    CAS  Google Scholar 

  54. Lloyd G., Sutton P.M., Atkinson T. (1988):Lancet 25, 1418.

    Article  Google Scholar 

  55. Fenner F., White D.O. (1970):Med. Virol. Academic Press.

  56. Herold B.C., Kirkpatrick R., Marcellino D., Travelstead A., Pilipenko K., Krasa H., Bremer J., Dong L.J., Cooper M.D. (1999):Antimicrob. Agents Chemother. 43, 745.

    Article  PubMed  CAS  Google Scholar 

  57. Kowdley K.V. (2000):Am. J. Med. 108, 481.

    Article  PubMed  CAS  Google Scholar 

  58. Poupon R.E., Balkau B., Eschwege E., Poupon R. (1991):N. Engl. J. Med. 324, 1548.

    Article  PubMed  CAS  Google Scholar 

  59. Poupon R.E., Lindor KD., Cauch-Dudek K., Dickson E.R., Poupon R., Heathcote E.J. (1997):Gastroenterology 113, 884.

    Article  PubMed  CAS  Google Scholar 

  60. Paumgartner G., Beuers U. (2002):Hepatology 36, 525.

    Article  PubMed  CAS  Google Scholar 

  61. Beuers U., Spengler U., Kruis W., Aydemir U., Wiebecke B., Heldwein W., Weinzier L.M., Pape G.R., Sauerbruch T., Paumgartner G. (1992):Hepatology 16, 707.

    Article  PubMed  CAS  Google Scholar 

  62. Ransohoff D.F., Gracie W.A. (1993):Annals Intern. Med. 119, 607.

    Google Scholar 

  63. Danzinger R.G., Hofmann A.F., Schoemfield L.J., Thistle J.L. (1972):N. Engl. J. Med. 286, 1.

    PubMed  CAS  Google Scholar 

  64. Makino I., Hashimoto H., Shinozaki K., Nakagawa S. (1975):Jpn. J. Gastroenterol. 72, 690.

    CAS  Google Scholar 

  65. Salen G., Nicolau G., Shefer S. (1973):Clin. Res. 21, 523.

    Google Scholar 

  66. Coyne M.J., Bonorris G.G., Goldstein L.J. (1976):J. Lab. Clin. Med. 87, 281.

    PubMed  CAS  Google Scholar 

  67. Angelin B., Ewerth S., Einarsson K. (1983):J. Upid Res. 24, 461, 1983.

    CAS  Google Scholar 

  68. W.G. Hardison, S.M. Grundy,Gastroenterology,87, 130.

  69. Maudgal D.P., Noithfield T.C. (1991):Drugs 41, 185.

    Article  PubMed  CAS  Google Scholar 

  70. Bell G.D., Dowling R.H., Whitney B., Sutor D.J. (1975):Gut 16, 359.

    Article  PubMed  CAS  Google Scholar 

  71. Maudgal D.P., Kupfer R.M., Northfield T.C. (1983):Gut 24, 1.

    Article  Google Scholar 

  72. Gonzalez-Koch A., Nervi F. (1998):World. Surg. 22, 1145.

    Article  CAS  Google Scholar 

  73. Maton P.N., Iser J.H., Reuben A., Saxton H.M., Murphy G.M., Dowling R.H. (1982):Medicine 61, 86.

    Article  PubMed  CAS  Google Scholar 

  74. Bouchier I.A.D. (1988):Gut 29, 137.

    Article  PubMed  CAS  Google Scholar 

  75. Salvioli G., Salati R., Lugli R., Zanni C. (1983):Gut 29, 609.

    Article  Google Scholar 

  76. Ros E., Navarro S., Bru C., Gilabert R., Bianchi L., Bruguera M. (1993):Lancet 342, 404.

    Article  PubMed  CAS  Google Scholar 

  77. Mok H.Y.I., Bell G.D., Dowling R.H. (1974):Lancet 2, 253.

    Article  PubMed  CAS  Google Scholar 

  78. Schoenfield L.J., Lachin J.M. (1981):Annals Intern. Med. 95, 257.

    CAS  Google Scholar 

  79. Lanzini A., Facchinetti D., Pigozzi M.G. (1991):Scand. J. Gastroenterol. 26, 551.

    Article  PubMed  CAS  Google Scholar 

  80. Maton P.N., Murphy G.M., Dowling R.H. (1977):Lancet 2, 1297.

    Article  PubMed  CAS  Google Scholar 

  81. Chadwick V.S., Gaginella T.S., Carlson G.L. (1979):J. Lab. Clin. Med. 94, 661.

    PubMed  CAS  Google Scholar 

  82. Bateson M.C., Bouchier I.A.D., Trash D.B. (1981):Br. Med. J. 283, 645.

    Article  CAS  Google Scholar 

  83. Villanova N., Bazzoli F., Taroni F., Frabboni R., Mazzella G., Festi D., Barbara L., Roda E. (1989):Gastroenterology 97, 726.

    PubMed  CAS  Google Scholar 

  84. Duan R.D., Erlanson-Albertson C. (1986):Scand. J. Gastroenterol. 21, 1211.

    Article  PubMed  CAS  Google Scholar 

  85. Duan R.D., Erlanson-Albertson C. (1985):Scand. J. Gastroenterol. 20, 1239.

    Article  PubMed  CAS  Google Scholar 

  86. Spraycar M. (ed.) (1995):Stedman’s Medical Dictionary. 26th Edition, Williams and Wilkins, New York.

    Google Scholar 

  87. Takeyama Y., Nakanishi H., Ohyanagi H., Saitoh Y., Kaibuchi K., Takai Y. (1986):J. Clin. Invest. 78, 1604.

    Article  PubMed  CAS  Google Scholar 

  88. Thimister P.W.L., Hopman W.P.M., Tangerman A., Rosenbusch G., Willems H.L., Jansen J.B.M.J. (1998):Hepatology 28, 1454.

    Article  PubMed  CAS  Google Scholar 

  89. Gomez G., Townsend C.M., Green D.W., Rajaraman S., Uchida T., Greeley G.H., Soloway R.D., Thompson J.C. (1990):J. Clin. Invest 86, 323.

    Article  PubMed  CAS  Google Scholar 

  90. Go V.L.W., Brooks F.P., Di Magno E.P., Gardner J.D., Lebenthal E., Scheele G.A. (eds) (1986):The Exocrine Pancreas: Biology, Pathobiology and Diseases. Raven Press, New York.

    Google Scholar 

  91. Holtmann G., Kelly D.G., Sternby B., Di Magno E.P. (1997):Am. J. Physiol.-Gastrointest. Liver Physiol.273, 553.

    Google Scholar 

  92. Vuoristo M., Vaananen H., Miettinen T.A. (1992):Gastroenterology 102, 647.

    PubMed  CAS  Google Scholar 

  93. Wickham M., Garrood M., Leney J., Wilson P.D.G., Fillery-Travis A. (1998):J. Lipid Res. 39, 623.

    PubMed  CAS  Google Scholar 

  94. Amigo L., Mardones P., Ferrada C, Zanlungo S., Nervi F., Miquel J.F., Rigotti A. (2003):Hepatology 38, 727.

    Article  CAS  Google Scholar 

  95. Hardcastle J., Hardcastle P., Chapman J., Taylor C. (2001):J. Pharm. Pharmacol. 53, 1457.

    Article  PubMed  CAS  Google Scholar 

  96. Reddy B.S. (1992):Lipids 27, 807.

    Article  PubMed  CAS  Google Scholar 

  97. Ochsenkuhn T., Bayerdorffer E., Meining A., Schinkel M., Thiede C., Nussler V., Sackmann M., Hätz R., Neubauer A., Paumgartner G. (1999):Cancer 85, 1665.

    Article  Google Scholar 

  98. Milovic V., Teller I.C., Faust D., Caspary W.F., Stein J. (2002):Eur. J. Clin. Invest. 32, 29.

    Article  PubMed  CAS  Google Scholar 

  99. Blobe G.C., Obeid L.M., Hannun Y.A. (1994):Cancer Metastasis Rev. 13, 411.

    Article  PubMed  CAS  Google Scholar 

  100. Rao Y.P., Stravitz R.T, Vlahcevic Z.R., Gurley E.C., Sando J.J., Hylemon P.B. (1997):J. Upid Res. 38, 2446.

    CAS  Google Scholar 

  101. Im E.O., Choi Y.H., Paik K.J., Suh H., Jin Y., Kim K.W., Yoo Y.H., Kim N.D. (2001):Cancer Lett. 163, 83.

    Article  PubMed  CAS  Google Scholar 

  102. Earnest D.L., Holubec H., Wali R.K., Jolley CS., Bissonette M., Bhattacharyya A.K., Roy H., Khare S., Brasitus T.A. (1994):Cancer Res. 54, 5071.

    PubMed  CAS  Google Scholar 

  103. Suh H., Jung E.J., Kim T.H., Lee H.Y., Park Y.H., Kim K.W. (1991):Cancer Lett., 113, 117.

    Article  Google Scholar 

  104. Choi Y.H., Im E.O., Suh H., Jin Y., Yoo Y.H., Kim N.D. (2003):Cancer Lett. 199, 157.

    Article  PubMed  CAS  Google Scholar 

  105. Kuhajda K., Kevresan S., Mikov M., Sabo A., Miljkovic D. (2000):Arch. Toxicol. Kinet. Xenobiotic Metab. 8, 304.

    Google Scholar 

  106. Mikov M., Kuhajda K., Kandrac J. (2003):Medicinski Pregled 56, 237.

    Article  PubMed  Google Scholar 

  107. 107. De Fabiani E.I., Mitro N., Godio C., Gilardi F., Caruso D., Crestani M. (2004):Biochimie 86, 111.

    Google Scholar 

  108. Li A.C., Glass C.K. (2004):J. Upid Res. 45, 2161.

    CAS  Google Scholar 

  109. Miljkovic D., Kuhajda D., Mikov M., Kevresan S., Sabo A. (2000):U. S. Pat. 6, 060, 465.

Download references

Author information

Authors and Affiliations

  1. School of Pharmacy, University of Otago, POB 913, 9054, Dunedin, New Zealand

    Mikov M.

  2. Medical Faculty and Department of Pharmacology and Toxicology, University of Novi Sad, Serbia

    Mikov M.

  3. School of Pharmacy, University of Otago, Dunedin, New Zealand

    Fawcett J. P.

  4. Research Center for Drug Metabolism, College of Life Science, Jilin University, Changchun, P.R China

    Fawcett J. P.

  5. Faculty of Science, Department of Biochemistry, University of Novi Sad, Serbia

    Kuhajda K.

  6. Faculty of Agricalture, Department of Chemistry, University of Novi Sad, Serbia

    Kevresan S.

Authors
  1. Mikov M.
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Fawcett J. P.
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Kuhajda K.
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Kevresan S.
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Mikov M..

Rights and permissions

Reprints and permissions

About this article

Cite this article

Mikov, M., Fawcett, J.P., Kuhajda, K. et al. Pharmacology of bile acids and their derivatives: Absorption promoters and therapeutic agents. Eur. J. Drug Metab. Pharmacokinet. 31, 237–251 (2006). https://doi.org/10.1007/BF03190714

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF03190714

Key words

Search

Navigation