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The Effect of Drugs on Liver Function and Biliary Secretion

  • Chapter
Biochemical Pharmacology as an Approach to Gastrointestinal Disorders

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Abstract

A number of different agents are used for the quantitative assessment of deranged hepatic function which includes abnormalities of:

  1. 1.

    Various metabolic processes

  2. 2.

    Hepatic flow, and

  3. 3.

    Biliary secretion.

In the last 10–15 years, we have gained considerable experience in assessing liver function in relation to the stage and/or the progression of chronic liver disease (CLD) by means of antipyrine clearance, the galactose elimination capacity and, more recently, the cytochrome P450-mediated formation of monoethy1g1ycinxylidide (MEGX) following lidocaine administration. The changes in the metabolism of these agents provide a useful tool to monitor the influence of other drugs (for example, silymarin, ursodeoxycholic acid and interferon) on CLD of different aetiology. Moreover, evaluation of drug metabolizing activity is also used to optimize the timing of liver transplantation and to quantify the functioning liver mass in potential liver donors. As regards biliary secretion, it is well known that a number of drugs may influence biliary flow, biliary lipid output and biliary bile acid composition. For example, ursodeoxycholic acid reduces biliary cholesterol secretion and is used as a litholytic agent for cholesterol gallstones. However, it is also beneficial in chronic cholestatic and noncholestatic liver disease because of its choleretic, membrane-stabilizing and immunomodulatory effects. Conversely, silymarin, which is currently used in the management of acute poisoning as well as of CLD, may be regarded as a potential litholytic agent since it reduces biliary cholesterol concentration and secretion. In conclusion, the study of the pharmacokinetics of different drugs may provide useful information to the clinicians about the stage and the progression of CLD. On the other hand, it seems important to evaluate the influence on biliary secretion of cytoprotective agents commonly used in the treatment of CLD with or without cholestatic features.

Correspondence

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References

  1. Jazrawi RP, de Caesteker JS, Goggin P et al. Kinetics of hepatic handling of cholestatic liver disease: effect of ursodeoxycholic acid. Gastroenterology. 1994; 5: 373–81.

    Google Scholar 

  2. Jazrawi BP, Ferraris R, Bridges C et al. Kinetics of the synthetic bile acid 75Se HCAT in man: comparison with 14C taurocholate. Gastroenterology. 1988; 95: 164–9.

    PubMed  CAS  Google Scholar 

  3. Galatola G, Jazrawi RP, Bridges C et al. Direct measurement of first-pass ileal clearance of a bile acid in humans. Gastroenterology. 1991; 100: 1100–5.

    PubMed  CAS  Google Scholar 

  4. Lirussi F, Nassuato G, Orlando R et al. Treatment of active cirrhosis with ursodeoxycholic acid and a free radical scavenger: a two year prospective study. Med Sci Res. 1995; 23: 31–3.

    Google Scholar 

  5. Lotterer E, Stiehl A, Raedsch R et al. Ursodeoxycholic acid in primary biliary cirrhosis: no evidence for toxicity in the stages Ito III. J Hepatol. 1990; 10: 284–90.

    Article  PubMed  CAS  Google Scholar 

  6. Leuschner U, Fischer H, Kurtz W et al. Ursodeoxycholic acid in primary biliary cirrhosis: results of a controlled double-blind trial. Gastroenterology. 1989; 97: 1268–74.

    PubMed  CAS  Google Scholar 

  7. Lirussi F, Bortolato L, Beccarello A, Okolicsanyi L, Crepaldi G. Long-term treatment with ursodeoxycholic acid (UDCA) of active cirrhosis. Efilcacy and evaluation of liver function (LF). Hepato Gastroenterology. 1993; III (Suppl 1): 75.

    Google Scholar 

  8. Williams SJ, Farrel GC. Inhibition of antipyrine metabolism by interferon. Br 7 Clin Pharmacol. 1986; 22: 610–12.

    Article  CAS  Google Scholar 

  9. Williams SJ, Baird-Lambert JA, Farrel GC. Inhibition of theophylline metabolism by interferon. Lancet. 1987; 2: 939–41.

    Article  PubMed  CAS  Google Scholar 

  10. Okuno H, Kitao Y, Takasu M et al. Depression of drug metabolizing activity in the human liver by interferon-a. Eur J Clin Pharmacol. 1990; 39: 365–7.

    Article  PubMed  CAS  Google Scholar 

  11. Okuno H, Takasu M, Kano H, Seki T, Shiozaki Y, Inoue K. Depression of drug-metabolizing activity in the human liver by interferon-ß. Hepatology. 1993; 17: 65–9.

    Article  PubMed  CAS  Google Scholar 

  12. Oellerich M, Raude E, Burdelski M et al. Monoethylglycinexylidide formation kinetics: A novel approach to assessment of liver function. J Clin Chem Clin Biochem. 1987; 25: 845–53.

    PubMed  CAS  Google Scholar 

  13. Oellerich M, Ringe B, Gubernatis G et al. Lignocaine metabolite formation as a measure of pretransplant liver function. Lancet. 1989; 1: 640–2.

    Article  PubMed  CAS  Google Scholar 

  14. Fabris L, Iemmolo RM, Viaggi S et al. Ability of monoethylglycinexylidide (MEGX) formation test in discriminating severity of liver cirrhosis. J Hepatol. 1994; 21 (Suppl 1): 5158.

    Google Scholar 

  15. Okamoto H, Sugiyama Y, Okada S et al. Typing hepatitis C virus by polymerase chain reaction with type-specific primers: Application to clinical surveys and tracing infectious sources. J Gen Vir. 1992; 73: 673–9.

    Article  CAS  Google Scholar 

  16. Lirussi F, Crovatto M, Santini G et al. Interferon (IFN), chronic hepatitis C and HCV genotypes. Any influence on liver function? Proceedings of the X International Congress of Liver Diseases: Acute and Chronic Liver Diseases: Molecular Biology and Clinics, Oct 19–21, Basel; 1995: 119.

    Google Scholar 

  17. Okolicsanyi L, Lirussi F, Strazzabosco M. et al. The effect of drugs on bile flow and composition. An overview. Drugs. 1986; 31: 430–48.

    CAS  Google Scholar 

  18. Nathanson MH, Boyer JL. Mechanisms and regulation of bile secretion. Hepatology. 1991; 14: 551–66.

    Article  PubMed  CAS  Google Scholar 

  19. Suchy FJ. Hepatocellular transport of bile acids. Semin Liver Dis. 1993; 13: 235–47.

    Article  PubMed  CAS  Google Scholar 

  20. Radominska A, Treat S, Little J. Bile acid metabolism and the pathophysiology of cholestasis. Semin Liver Dis. 1993; 13: 219–34.

    Article  PubMed  CAS  Google Scholar 

  21. Kamimoto Y, Gatmaitan Z, Hsu J, Arias IM. The function of Gp170, the multidrug resistance gene product, in rat liver canalicular membrane vesicles. J Biol Chem. 1989; 264: 11693–8.

    PubMed  CAS  Google Scholar 

  22. Elias E, Hruban Z, Wade JB, Boyer JL. Phalloidin-induced cholestasis: a microfilament-mediated change in junctional complex permeability. Proc Natl Acad Sci USA. 1980: 77: 2229 33.

    Google Scholar 

  23. Boyer JL. Tight junction in normal and cholestatic liver: does the paracellular pathway have functional significance? Hepatology. 1983; 3: 614–7.

    Article  PubMed  CAS  Google Scholar 

  24. Beuers U, Nathanson MH, Boyer JL. Effects of tauroursodeoxycholic acid on cytosolic Ca2+ signals in isolated rat hepatocytes. Gastroenterology. 1993; 104: 604–12.

    PubMed  CAS  Google Scholar 

  25. Strazzabosco M, Okolicsanyi L, Boyer JL. Acid/base transport systems in isolated bile duct epithelial cells. In: Gentilini P, Dianzani MU, eds. Experimental and Clinical Hepatology. Amsterdam: Elsevier; 1991: 133–41.

    Google Scholar 

  26. Gautam A, Ng OC, Boyer JL. Isolated rat hepatocyte couplets in short-term culture: structural characteristics and plasma membrane reorganization. Hepatology. 1987; 7: 216–23.

    Article  PubMed  CAS  Google Scholar 

  27. Gautam A, Ng OC, Strazzabosco M, Boyer JL. Quantitative assessment of canalicular bile formation in isolated rat hepatocyte couplets using microscopic optical planimetry. J Clin Invest. 1989; 83: 565–73.

    Article  PubMed  CAS  Google Scholar 

  28. Strazzabosco M, Sakisaka S, Hayakawa T, Boyer JL. Effect of UDCA on intracellular and biliary pH in isolated rat hepatocyte couplets and perfused livers. Am J Physiol. 1991; 260: G58–69.

    PubMed  CAS  Google Scholar 

  29. Poupon RE, Poupon R, Balkau B and the UDCA-PBC Study Group. Ursodiol for the long-term treatment of primary biliary cirrhosis. N Engl J Med. 1994;330:1342–7.

    Article  PubMed  CAS  Google Scholar 

  30. Reichen J. Pharmacologic treatment of cholestasis. Semin Liver Dis. 1993; 13: 302–15.

    Article  PubMed  CAS  Google Scholar 

  31. Lirussi F, Okolicsanyi L. Cytoprotection with ursodeoxycholic acid: effect in chronic non-cholestatic and chronic cholestatic liver disease. Ital J Gastroenterol. 1992; 24: 31–5.

    PubMed  CAS  Google Scholar 

  32. Jacquemin E, Dumont M, Mallet A, Erlinger S. Ursodeoxycholic acid improves ethinyl estradiolinduced cholestasis in the rat. Eur J Clin Invest. 1993; 23: 794–802.

    Article  PubMed  CAS  Google Scholar 

  33. 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.

    PubMed  CAS  Google Scholar 

  34. Poupon RE, Balkau B, Eschwège E, Poupon R and the UDCA-PBC Study Group. A multicenter, controlled trial of ursodiol for the treatment of primary biliary cirrhosis. N Engl J Med 1991; 324:1548–54.

    Article  PubMed  CAS  Google Scholar 

  35. Leuschner U, Leuschner M, Sieratzki J, Kurtz W, Hubner K. Gallstone dissolution with ursodeoxycholic acid in patients with chronic active hepatitis and two years follow-up. Dig Dis Sci. 1985; 30: 6429.

    Article  Google Scholar 

  36. Ferenci P, Dragosics B, Dittrich H et al. Randomized controlled trial of silymarin treatment in patients with cirrhosis of the liver. J Hepatol. 1989; 9: 105–13.

    Article  PubMed  CAS  Google Scholar 

  37. Nassuato G, Iemmolo RM, Strazzabosco M et al. Effect of silibinin on biliary lipid composition. Experimental and clinical study. J Hepatol. 1991; 12: 290–5.

    Article  PubMed  CAS  Google Scholar 

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Author information

Authors and Affiliations

  1. Institute of Internal Medicine, University of Padova, Padova, Italy

    F. Lirussi

  2. University of Parma, Parma, Italy

    L. Okolicsanyi (Chair of Gastroenterology)

Authors
  1. F. Lirussi
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  2. L. Okolicsanyi
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Editor information

Editors and Affiliations

  1. School of Pharmacy, University of Wisconsin, Madison, WI, USA

    Timothy S. Gaginella

  2. First Department of Medicine, University Medical School of Pécs, Pécs, Hungary

    Gyula Mózsik

  3. Department of Biomedical Sciences, Sheffield Hallam University, Sheffield, UK

    K. D. Rainsford

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© 1997 Springer Science+Business Media Dordrecht

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Lirussi, F., Okolicsanyi, L. (1997). The Effect of Drugs on Liver Function and Biliary Secretion. In: Gaginella, T.S., Mózsik, G., Rainsford, K.D. (eds) Biochemical Pharmacology as an Approach to Gastrointestinal Disorders. Springer, Dordrecht. https://doi.org/10.1007/978-94-011-5390-4_19

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  • DOI: https://doi.org/10.1007/978-94-011-5390-4_19

  • Publisher Name: Springer, Dordrecht

  • Print ISBN: 978-94-010-6267-1

  • Online ISBN: 978-94-011-5390-4

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