Skip to main content
SpringerLink
Log in

Hepatic Drug Metabolism and Drug Toxicity

  • Chapter
Clinical Hepatology

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

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 89.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Ando Y, Saka H, Asai G, et al (1998) UGT1A1 genotypes and glucuronidation of SN-38, the active metabolite of irinotecan. Ann Oncol 9: 845–7

    Article  CAS  PubMed  Google Scholar 

  2. Bosma PJ, Chowdhury JR, Bakker C, et al (1995) The genetic basis of the reduced expression of bilirubin UDP- glucurono-syltransferase 1 in Gilbert's syndrome. N Engl J Med 333: 1171–5

    Article  CAS  PubMed  Google Scholar 

  3. Chouinard S, Tessier M, Vernouillet G, et al (2006) Inactivation of the pure antiestrogen fulvestrant and other synthetic estrogen molecules by UDP-glucuronosyltransferase 1A enzymes expressed in breast tissue. Mol Pharmacol 69: 908–20

    CAS  PubMed  Google Scholar 

  4. Ciotti M, Basu N, Brangi M, et al (1999) Glucuronidation of 7-ethyl-10-hydroxycamptothecin (SN-38) by the human UDP-glucuronosyltransferases encoded at the UGT1 locus. Biochem Biophys Res Commun 260: 199–202

    Article  CAS  PubMed  Google Scholar 

  5. Dancygier H, Frühauf H (1997) Klinische Pharmakologie der Leberkrankheiten. In: Kuemmerle HP (ed) Klinische Pharmakologie, 4th edn. Ecomed Verlag, Munich, IV-4.11.1, pp 1–77

    Google Scholar 

  6. Douillard JY, Cunningham D, Roth AD, et al (2000) Irinotecan combined with fluorouracil compared with fluorouracil alone as first-line treatment for metastatic colorectal cancer: a mul-ticentre randomised trial. Lancet 355: 1041–7

    Article  CAS  PubMed  Google Scholar 

  7. Ebner T, Remmel RP, Burchell B (1993) Human bilirubin UDP-glucuronosyltransferase catalyzes the glucuronidation of ethinylestradiol. Mol Pharmacol 43: 649–54

    CAS  PubMed  Google Scholar 

  8. Ehmer U, Vogel A, Schutte JK, et al (2004) Variation of hepatic glucuronidation: novel functional polymorphisms of the UDP-glucuronosyltransferase UGT1A4. Hepatology 39: 970–7

    Article  CAS  PubMed  Google Scholar 

  9. Folprecht G, Kohne CH (2004) The role of new agents in the treatment of colorectal cancer. Oncology 66: 1–17

    Article  CAS  PubMed  Google Scholar 

  10. Gagne JF, Montminy V, Belanger P, et al (2002) Common human UGT1A polymorphisms and the altered metabolism of irinotecan active metabolite 7-ethyl-10-hydroxycamp-tothecin (SN-38). Mol Pharmacol 62: 608–17

    Article  CAS  PubMed  Google Scholar 

  11. Gennis MA, Vemuri R, Burns EA, et al (1991) Familial occurrence of hypersensitivity to phenytoin. Am J Med 91: 631–4

    Article  CAS  PubMed  Google Scholar 

  12. Ghosal A, Hapangama N, Yuan Y, et al (2004) Identification of human UDP-glucuronosyltransferase enzyme(s) responsible for the glucuronidation of ezetimibe (Zetia). Drug Metab Dispos 32: 314–20

    Article  CAS  PubMed  Google Scholar 

  13. Gillette JR, Stripp B (1975) Pre- and postnatal enzyme capacity for drug metabolic production. Fed Proc 34: 172–8

    CAS  PubMed  Google Scholar 

  14. Givens RC, Watkins PB (2003) Pharmacogenetics and clinical gastroenterology. Gastroenterology 125: 240–8

    Article  CAS  PubMed  Google Scholar 

  15. Hoft RH, Bunker JP, Goodman HI, et al (1981) Halothan hepatitis in three pairs of closely related women. N Engl J Med 304: 1023–4

    Article  CAS  PubMed  Google Scholar 

  16. Innocenti F, Ratain MJ (2003) Irinotecan treatment in cancer patients with UGT1A1 polymorphisms. Oncology 17: 52–5

    PubMed  Google Scholar 

  17. Innocenti F, Undevia SD, Iyer L, et al (2004) Genetic variants in the UDP-glucuronosyltransferase 1A1 gene predict the risk of severe neutropenia of irinotecan. J Clin Oncol 22: 1382–8

    Article  CAS  PubMed  Google Scholar 

  18. Iyer L, King CD, Whitington PF, et al (1998) Genetic predisposition to the metabolism of irinotecan (CPT-11). Role of uridine diphosphate glucuronosyltransferase isoform 1A1 in the glucuronidation of its active metabolite (SN-38) in human liver microsomes. J Clin Invest 101: 847–54

    Article  CAS  PubMed  Google Scholar 

  19. Karliova M, Treichel U, Malagò M, et al (2000) Interaction of Hypericum perforatum (St. John's wort) with cyclosporin A metabolism in a patient after liver transplantation. J Hepatol 33: 853–5

    Article  CAS  PubMed  Google Scholar 

  20. Kawato Y, Aonuma M, Hirota Y, et al (1991) Intracellular roles of SN-38, a metabolite of the camptothecin derivative CPT-11, in the antitumor effect of CPT-11. Cancer Res 51: 4187–91

    CAS  PubMed  Google Scholar 

  21. King CD, Green MD, Rios GR, et al (1996) The glucuroni-dation of exogenous and endogenous compounds by stably expressed rat and human UDP-glucuronosyltransferase 1.1. Arch Biochem Biophys 332: 92–100

    Article  CAS  PubMed  Google Scholar 

  22. Kohle C, Mohrle B, Munzel PA, et al (2003) Frequent co-occurrence of the TATA box mutation associated with Gilbert's syndrome (UGT1A1*28) with other polymorphisms of the UDP-glucuronosyltransferase-1 locus (UGT1A6*2 and UGT1A7*3) in Caucasians and Egyptians. Biochem Pharmacol 65: 1521–7

    Article  CAS  PubMed  Google Scholar 

  23. Kuehl GE, Lampe JW, Potter JD, et al (2005) Glucuronidation of nonsteroidal anti-inflammatory drugs: identifying the enzymes responsible in human liver microsomes. Drug Metab Dispos 33: 1027–35

    Article  CAS  PubMed  Google Scholar 

  24. Lampe JW, Bigler J, Horner NK, et al (1999) UDP-glucuronosyltransferase (UGT1A1*28 and UGT1A6*2) polymorphisms in Caucasians and Asians: relationships to serum bilirubin concentrations. Pharmacogenetics 9: 341–9

    Article  CAS  PubMed  Google Scholar 

  25. Lankisch TO, Moebius U, Wehmeier M, et al (2006) Gilbert's disease and atazanavir: from phenotype to UDP-glucuronosyltransferase haplotype. Hepatology 44: 1324–32

    Article  CAS  PubMed  Google Scholar 

  26. Lankisch TO, Schulz C, Zwingers T, et al (2008) Gilbert's syndrome and Irinotecan toxicity: combination with UDP-glucuronosyltransferase 1A7 variants increases risk. Cancer Epidemiol Biomarkers Prev 17: 695–701

    Article  CAS  PubMed  Google Scholar 

  27. Lankisch TO, Vogel A, Eilermann S, et al (2005) Identification and characterization of a functional TATA box polymorphism of the UDP glucuronosyltransferase 1A7 gene. Mol Pharmacol 67: 1732–39

    Article  CAS  PubMed  Google Scholar 

  28. Monaghan G, Ryan M, Seddon R, et al (1996) Genetic variation in bilirubin UPD-glucuronosyltransferase gene promoter and Gilbert's syndrome. Lancet 347: 578–81

    Article  CAS  PubMed  Google Scholar 

  29. Ogilvie BW, Zhang D, Li W, et al (2006) Glucuronidation converts gemfibrozil to a potent, metabolism-dependent inhibitor of cyp2c8: implications for drug-drug interactions. Drug Metab Dispos 34: 191–7

    Article  CAS  PubMed  Google Scholar 

  30. Pelekonen O, Kalhala EH, Lormi TKJ, et al (1973) Comparison of activities of drug metabolizing enzymes in human fetal and adult livers. Clin Pharmacol Ther 14: 840–4

    Google Scholar 

  31. Prueksaritanont T, Subramanian R, Fang X, et al (2002) Glucuronidation of statins in animals and humans: a novel mechanism of statin lactonization. Drug Metab Dispos 30: 505–12

    Article  CAS  PubMed  Google Scholar 

  32. Rotger M, Taffe P, Bleiber G, et al (2005) Gilbert syndrome and the development of antiretroviral therapy-associated hyperbilirubinemia. J Infect Dis 192: 1381–6

    Article  CAS  PubMed  Google Scholar 

  33. Schenker S, Bay M (1994) Drug disposition and hepatotox-icity in the elderly. J Clin Gastroenterol 18: 232–7

    Article  CAS  PubMed  Google Scholar 

  34. Strassburg CP, Manns MP (2000) Jaundice, genes and promoters. J Hepatology 33: 476–9

    Article  CAS  Google Scholar 

  35. Tukey RH, Strassburg CP (2001) Genetic multiplicity of the human UDP-glucuronosyltransferases and regulation in the gastrointestinal tract. Mol Pharmacol 59: 405–14

    CAS  PubMed  Google Scholar 

  36. Tukey RH, Strassburg CP (2000) Human UDP-glucuronosyl-transferases: metabolism, expression, and disease. Annu Rev Pharmacol Toxicol 40: 581–616

    Article  CAS  PubMed  Google Scholar 

  37. Tukey RH, Strassburg CP, Mackenzie PI (2002) Pharma-cogenomics of human UDP-glucuronosyltransferases and irinotecan toxicity. Mol Pharmacol 62: 446–50

    Article  CAS  PubMed  Google Scholar 

  38. Weinshilbourn R (2003) Inheritance and drug response. N Engl J Med 348: 529–37

    Article  CAS  Google Scholar 

  39. Woodhouse KW, Mutch E, Williams FM, et al (1984) The effect of age on pathways of drug metabolism in human liver. Age Ageing 13: 328–34

    Article  CAS  PubMed  Google Scholar 

  40. Zhang D, Chando TJ, Everett DW, et al (2005) In vitro inhibition of UDP glucuronosyltransferases by atazanavir and other HIV protease inhibitors and the relationship of this property to in vivo bilirubin glucuronidation. Drug Metab Dispos 33: 1729–39

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Chair, Department of Medicine II, Klinikum Offenbach, Goethe University Frankfurt/Main, Starkenburgring 66, Offenbach, 63069, Germany

    Henryk Dancygier (Professor of Medicine)

  2. Department of Medicine, Division of Liver Diseases, Mount Sinai School of Medicine, New York, NY, USA

    Henryk Dancygier (Professor of Medicine)

  3. Department of Gastroenterology, Hepatology and Endocrinology, University Hannover Medical School, Carl-Neuberg-Str. 1, Hannover, 30625, Germany

    Christian P. Strassburg

Authors
  1. Henryk Dancygier
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Christian P. Strassburg
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

Copyright information

© 2010 Springer-Verlag Berlin Heidelberg

About this chapter

Cite this chapter

Dancygier, H., Strassburg, C.P. (2010). Hepatic Drug Metabolism and Drug Toxicity. In: Clinical Hepatology. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-04519-6_38

Download citation

  • DOI: https://doi.org/10.1007/978-3-642-04519-6_38

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-642-04509-7

  • Online ISBN: 978-3-642-04519-6

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation