Pharmacogenomics in Relation to Tailor-made Drugs

  • Satoh, Tetsuo (Chiba University and Human and Animal Bridging Research Institute)
  • 발행 : 2006.12.30

초록

The field of cytochrome P450 pharmacogenomics has progressed rapidly during the past 25 years. Recently, conjugating enzymes including sulfotransferase, acetyltransferase, glucuronosyltransferase and glutathione transferase have been also extensively studied. All the major human drug-metabolizing P450 enzymes and some conjugating enzymes have been identified and cloned, and the major gene variants that cause inter-individual variability in drug response and are related to adverse drug reactions have been identified. This information now provides the basis for the use of predictive pharmacogenomics to yield drug therapies that are more efficient and safer. Today, we understand which drugs warrant dosing based on pharmacogenomics to improve drug treatment. It is anticipated that genotyping could be used to personalize drug treatment for vast numbers of subjects, decreasing the cost of drug treatment and increasing the efficacy of drugs and health in general. It is assumed that such personalized P450 gene-based treatment which is so-called tailor(order)-made drug therapy would be relevant for 10-20% of all drug therapy in the future.

키워드

참고문헌

  1. Bracco, L. and Kearsey, J. (2003) The relevance of alternative RNA splicing to pharmacogenomics. Trends Biotechnol. 21, 346-353 https://doi.org/10.1016/S0167-7799(03)00146-X
  2. Evans W.E.(1999) Pharmacogenomics: Translating functional genomics into national therapeutics. Science 286, 487-491 https://doi.org/10.1126/science.286.5439.487
  3. Fukushima-Uesaka, H. et al. (2004) Haplotypes of CYP3A4 and their close linkage with CYP3A5 haplotypes in a Japanese population. Hum. Mutat. 23, 100 https://doi.org/10.1002/humu.9210
  4. Funk, C., Pantze, M., Jehle, L., Ponelle, C., Scheuermann, G., Lazendic, M., Gasser, R.(2001).Troglitazone-induced intrahepatic cholestasis by an interference with the hepatobiliary export of bile acids in male and female rats. Correlation with the gender difference in troglitazone sulfate formation and the inhibition of the canalicular bile salt export pump (Bsep) by troglitazone and troglitazone sulfate. Toxicology. 167, 83-98 https://doi.org/10.1016/S0300-483X(01)00460-7
  5. Ingelman-Sundberg, M. (2004) Human drug metabolising cytochrome P450 enzymes: properties and polymorphisms. Naunyn Schmiedebergs Arch. Pharmacol. 369, 89-104 https://doi.org/10.1007/s00210-003-0819-z
  6. Kaneko, A., Lum, J.K., Yaviong, J. (1999): High and variable frequencies of CYP2C 19 mutations: Medical consequences of poor drug metabolism in Vanuatu and other Pacific islands. Pharmacogenetics 9, 81-590 https://doi.org/10.1097/00008571-199902000-00011
  7. Kassahun, K., Pearson, P., Tang, W., McIntosh, I., Leung, K., Elmore, C., Dean, D., Wang, R., Doss, G., and Baillie, T.A. (2001). Studies on the metabolism of Troglitazone to reactive intermediates in vitro and in vivo. Evidence for novel biotransformation pathways involving quinone methide formation and Thiazolidinedione ring scission. Chem. Res. Toxicol. 14, 62-70 https://doi.org/10.1021/tx000180q
  8. Kato, R.. and Yamazoe, Y. (1994): The importance of substrate concentration in determing cytochrome P450 therapeutically relevant in vivo. Pharmacogenetics 4, 359-362 https://doi.org/10.1097/00008571-199412000-00010
  9. Kirchheiner J, Nickchen K, Bauer M, Licinio J, Wong M-L, Roots I, Brockmoller J. Therapeutic implications from pharmacogenetics in antidepressant and antipsychotic drug therapy. Mol Psychiatry (in press)
  10. La Du B.N.(1992): Human serum paraoxonase/arylesterase. In Kalow, W.(ed.): Pharmacogenetics of Drug Metabolism. New York; Pergamon Press, pp51-91
  11. Lesko, L.J. et al. (2003) Pharmacogenetics and pharmacogenomics in drug development and regulatory decision making: report of the first FDA-PWG-PhRMA-DruSafe Workshop. J. Clin. Pharmacol. 43, 342-358 84
  12. Lockridge, O. (1992): Genetic variants of human serum butyrylcholinesterase influence the metablolism of the muscle relaxant succinylcholine. In Kalow W.(ed.). Pharmacogenetics of Drug Metabolism. Pergamon Press. 15-50
  13. Mayer U.(2000) Lancet 356, 1667 https://doi.org/10.1016/S0140-6736(00)03167-6
  14. Mayer U. Lancet 356:1667, 2000Meyer, W.A.(1994): The molecular basis of genetic polymorphisms of drug metabolism. J. Pharm. Pharmacol. 46, (Suppl. 1) 409-415
  15. Ozdemir, V. et al. (2000) Evaluation of the genetic component of variability in CYP3A4 activity: a repeated drug administration method. Pharmacogenetics 10, 373-388 https://doi.org/10.1097/00008571-200007000-00001
  16. Phillips, K.A. et al. (2001) Potential role of pharmacogenomics in reducing adverse drug reactions: a systematic review. J. Am. Med. Assoc. 286, 2270-2279 https://doi.org/10.1001/jama.286.18.2270
  17. Pirmohamed, M. and Park, B.K. (2003) Cytochrome P450 enzyme polymorphisms and adverse drug reactions. Toxicology 192, 23-32 https://doi.org/10.1016/S0300-483X(03)00247-6
  18. Smith, G., Stubbins, M.J., Harris, L.W, Wolf, C.R.(1998): Molecular genetics of the human cytochrome P450 monooxygenase superfamily. Xenobiotica 8, 1129-1165
  19. Spear, B.B. et al. (2001) Clinical application of pharmacogenetics. Trends Mol. Med. 7, 201-204 https://doi.org/10.1016/S1471-4914(01)01986-4
  20. Toyoda, Y., Tsuchida, A., Iwami, E., and Miwa, I., (2001): Toxic effect of troglitazone on cultured rat hepatocytes. Life Sci., 68, 1867-1876 https://doi.org/10.1016/S0024-3205(01)00985-7
  21. Tucker, G.T. (1994): Clinical implications of genetic polymorphism in drug metabolism. J. Pharm. Pharmacol. 46(Suppl 1), 417-424
  22. Van Schaik, R.H.N. et al. (2003) CYP3A4, CYP3A5 and MDR-1 variant alleles in the Dutch Caucasian population. Clin. Pharmacol. Ther. 73, 42
  23. Vatsis, K.P., Weber, W.W., Bell, D.A. et al.(2000): Nomenclature for N-acetyltransferases. Pharmacogenetics 10, 291-292 https://doi.org/10.1097/00008571-200006000-00002
  24. Weinshilboum, R. (2003) Inheritance and drug response. New Engl. J. Med. 348, 529-537 https://doi.org/10.1056/NEJMra020021
  25. Yamamoto, Y., Yamazaki, H., Ikeda ,T., Watanabe, T., Iwabuchi, H., Nakajima, M., and Yokoi, T. (2002) Formation of a novel quinone epoxide metabolite of Troglitazone with cytotoxic to HepG2 cells. Drug Metab. Dispos, 30, 155-160 https://doi.org/10.1124/dmd.30.2.155
  26. Yates C.R. et al. (1997) Molecular diagnosis of thiopurine Smethyltransferase deficiency:genetic basis for azathioprine and mercaptopurine intolerance. Ann. Intern. Med. 126, 60-614