The Pharmacogenetics of Cytochrome P-450 and its Effect on Drug Metabolism

  • DIA AHAK M BEREWELA Department of Pharmaceutical Chemistry, Department of Pharmacology, Faculty of Pharmacy, Misurata University, Misurata 2478, Libya

Abstract

Cytochrome P-450 (CYP-450) enzyme plays an essential role in the oxidation of most drugs, and thus it can affect the toxicity and efficacy of many medications. Factors that influence the function and presence of cytochrome have a key impact on the outcomes of therapy. More specifically, characteristics of cytochrome pharmacogenetics and procedures of cytochrome enzymes induction and inhibition can greatly influence the rate of drug biotransformation and the rate of elimination. So, an understanding of genetic variants which are associated with drug responses and illnesses could improve and enhance the outcome of treatment. Clinical data in genetic tests may be useful in order to develop methods for assessing genetic risks. Positively, genetic tests for monogenic sicknesses have already proven to be a useful test and any changes may trigger a new field of personalized drug. This review will look at the influence of pharmacogenetics in drug metabolism and the importance of using personal genetic data in achieving optimal therapy and in preventing any possible adverse effects.


Keywords: Pharmacogenetics, Biotransformation, CYP-450

Keywords: Pharmacogenetics, Biotransformation, CYP-450

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Author Biography

DIA AHAK M BEREWELA, Department of Pharmaceutical Chemistry, Department of Pharmacology, Faculty of Pharmacy, Misurata University, Misurata 2478, Libya

Department of Oncology, Department of Continuing Education, Oxford University, Oxford, UK

References

1. Court, M. Interindividual variability in hepatic drug glucuronidation: studies into the role of age, sex, enzyme inducers, and genetic polymorphism using the human liver bank as a model system. Drug Metabolism Reviews, 2010; 42(1):209-224.
2. Meyer, U. Pharmacogenetics and adverse drug reactions. The Lancet, 2000; 356(9242):1667-1671.
3. Maggo, M., Kennedy, M. and Clark, D. Clinical implications of pharmacogenetic variation on the effects of statins. Drug Safety, 2011; 34(1):1-19.
4. Murray, M. Role of CYP pharmacogenetics and drug‐drug interactions in the efficacy and safety of atypical and other antipsychotic agents. Journal of Pharmacy and Pharmacology, 2006; 58(7):871-885.
5. Ingelman-Sundberg, M., Sim, S.C., Gomez, A. and Rodriguez-Antona, C. Influence of cytochrome P450 polymorphisms on drug therapies: pharmacogenetic, pharmacoepigenetic and clinical aspects. Pharmacology & Therapeutics, 2007; 116(3):496-526.
6. Mega, J., Close, S., Wiviott, S., Shen, L., Hockett, R., Brandt, J., et al. Cytochrome p-450 polymorphisms and response to clopidogrel. New England Journal of Medicine, 2009; 360(4):354-362.
7. Salari, K., Watkins, H. and Ashley, E. Personalized medicine: hope or hype? European Heart Journal, 2012; 33(13):1564-1570.
8. Ingelman-sundberg, M. Pharmacogenetics of cytochrome P450 and its applications in drug therapy: the past, present and future. Trends in Pharmacological Sciences, 2004; 25(4):193-200.
9. Nelson, David R., et al. P450 superfamily: update on new sequences, gene mapping, accession numbers and nomenclature. Pharmacogenetics and Genomics, 1996; 6(1):1-42.
10. Roots, I., Gerloff, T., Meisel, C., Kirchheiner, J., Goldammer, M., Kaiser, R., et al. Pharmacogenetics‐based new therapeutic concepts. Drug Metabolism Reviews, 2004; 36(3-4):617-638.
11. Zanger, U., Raimundo, S. and Eichelbaum, M. Cytochrome P450 2D6: overview and update on pharmacology, genetics, biochemistry. Naunyn-schmiedeberg's Archives of Pharmacology, 2004; 369(1):23-37.
12. Lam, L., Garcia-Barcelo, M., Ungvari, G., Tang, W., Lam, V., Kwong, S., et al. Cytochrome P450 2D6 genotyping and association with tardive dyskinesia in Chinese schizophrenic patients. Pharmacopsychiatry, 2001; 34(6):238-241.
13. Yu, A., Kneller, B., Rettie, A. and Haining, R. Expression, purification, biochemical characterization, and comparative function of human cytochrome P450 2D6.1, 2D6.2, 2D6.10, and 2D6.17 allelic isoforms. The Journal of Pharmacology and Experimental Therapeutics, 2002; 303(3):1291-1300.
14. Jose de Leon, M., Susce, M., Pan, R., Fairchild, M., Koch, W. and Wedlund, P. The CYP2D6 poor metabolizer phenotype may be associated with risperidone adverse drug reactions and discontinuation. J Clin Psychiatry, 2005; 66(1):15-27.
15. Spina, E., Scordo, M. and D'arrigo, C. Metabolic drug interactions with new psychotropic agents. Fundamental & Clinical Pharmacology, 2003; 17(5):517-538.
16. Gurbel, P., Bliden, K., Hiatt, B. and O’Connor, C. Clopidogrel for coronary stenting: response variability, drug resistance, and the effect of pretreatment platelet reactivity. Circulation, 2003; 107(23):2908-2913.
17. Matetzky, S., Shenkman, B., Guetta, V., Shechter, M., Beinart, R., Goldenberg, I., et al. Clopidogrel resistance is associated with increased risk of recurrent atherothrombotic events in patients with acute myocardial infarction. Circulation, 2004; 109(25):3171-3175.
18. Hulot, J., Bura, A., Villard, E., Azizi, M., Remones, V., Goyenvalle, C., et al. Cytochrome P450 2C19 loss-of-function polymorphism is a major determinant of clopidogrel responsiveness in healthy subjects. Blood, 2006; 108(7):2244-2247.
19. Simon, T., Verstuyft, C., Mary-Krause, M., Quteineh, L., Drouet, E., Méneveau, N., et al. Genetic determinants of response to clopidogrel and cardiovascular events. New England Journal of Medicine, 2009; 360(4):363-375.
20. Wallentin, L., James, S., Storey, R., Armstrong, M., Barratt, B.J., Horrow, J., et al Effect of CYP2C19 and ABCB1 single nucleotide polymorphisms on outcomes of treatment with ticagrelor versus clopidogrel for acute coronary syndromes: a genetic substudy of the PLATO trial. The Lancet, 2010; 376(9749):1320-1328.
21. Paré, G., Mehta, S., Yusuf, S., Anand, S., Connolly, S., Hirsh, J., et al. Effects of CYP2C19 genotype on outcomes of clopidogrel treatment. New England Journal of Medicine, 2010; 363(18):1704-1714.
22. Khan, A. and Preskorn, S. Examining Concentration-Dependent Toxicity of Clozapine: Role of Therapeutic Drug Monitoring. Journal of Psychiatric Practice, 2005; 11(5):289-301.
23. Esposito, D., Rouillon, F. and Limosin, F. Continuing clozapine treatment despite neutropenia. European journal of clinical pharmacology, 2005; 60(11):759-764.
24. Dain, J., Nicoletti, J. and Ballard, F. Biotransformation of clozapine in humans. Drug Metabolism and Disposition: The biological fate of chemicals, 1997; 25(5):603-609.
25. Tugnait, M., Hawes, E. McKay, G., Eichelbaum, M. and Midha, K. Characterization of the human hepatic cytochromes P450 involved in the in vitro oxidation of clozapine. Chemico-Biological Interactions, 1999; 118(2):171-189.
26. Raaska, K., Raitasuo, V., Laitila, J. and Neuvonen, P. Effect of Caffeine‐Containing versus Decaffeinated Coffee on Serum Clozapine Concentrations in Hospitalised Patients. Basic & Clinical Pharmacology & Toxicology, 2004; 94(1):13-18.
27. Faber, M. and Fuhr, U. Time Response of Cytochrome P450 1A2 Activity on Cessation of Heavy Smoking. Clinical Pharmacology & Therapeutics, 2004; 76(2):178-184.
28. Desai, H., Seabolt, J. and Jann, M. Smoking in Patients Receiving Psychotropic Medications. Springer, 2001; 15(6):469-494.
29. Mookhoek, E. and Loonen, A. Retrospective evaluation of the effect of omeprazole on clozapine metabolism. Pharmacy World and Science, 2004; 26(3):180-182.
30. Eap, C., Bender, S., Sirot, E., Cucchia, G., Jonzier-Perey, M., Baumann, P., et al. Nonresponse to clozapine and ultrarapid CYP1A2 activity: clinical data and analysis of CYP1A2 gene. Journal of Clinical Psychopharmacology, 2004; 24(2):214-219.
31. Allorge, D., Chevalier, D., Lo‐Guidice, J. M., Cauffiez, C., Suard, F., Baumann, P., et al. Identification of a Novel Splice‐site Mutation in the CYP1A2 Gene. British Journal of Clinical Pharmacology, 2003; 56(3):341-344.
32. Kootstra-ros, J., Smallegoor, W. and van der weide, J. The Cytochrome P450 CYP1A2 Genetic Polymorphisms *1F and *1D do not Affect Clozapine Clearance in a Group of Schizophrenic Patients. Annals of Clinical Biochemistry, 2005; 42(3):216-219.
33. Olesen, O. and Linnet, K. Contributions of Five Human Cytochrome P450 Isoforms to the N‐demethylation of Clozapine in Vitro at Low and High Concentrations. The Journal of Clinical Pharmacology, 2001; 41(8):823-832.
34. Chong, S., Tan, C. and Lee, H. Hoarding and Clozapine–Risperidone Combination. Canadian Journal of Psychiatry 1996; 41:315–316.
35. Tyson, S., Devane, C., and Risch, S. Pharmacokinetic Interaction between Risperidone and Clozapine. The American Journal of Psychiatry, 1995; 15:1401–1402.
36. Raskin, S., Katz, G., Zislin, Z., Knobler, H. and Durst, R. Clozapine and Risperidone: combination/augmentation treatment of refractory schizophrenia: a preliminary observation. Acta Psychiatrica Scandinavica, 2000; 101(4):334-336.
37. Wysowski, D., Nourjah, P. and Swartz, L. Bleeding Complications with Warfarin Use: a prevalent adverse effect resulting in regulatory action. Archives of Internal Medicine, 2007; 167(13):1414-1419.
38. Anderson, J., Horne, B., Stevens, S., Grove, A., Barton, S., Nicholas, Z., Kahn, S., et al. Randomized Trial of Genotype-guided versus Standard Warfarin Dosing in Patients Initiating Oral Anticoagulation. Circulation, 2007; 116(22):2563-2570.
39. International Warfarin Pharmacogenetics Consortium. Estimation of the Warfarin Dose with Clinical and Pharmacogenetic Data. The New England Journal of Medicine, 2009; 360(8):753-764.
40. Siegel, D., Lopez, J. and Meier, J. Use of Cholesterol-Lowering Medications in the United States from 1991 to 1997. The American Journal of Medicine, 2000; 108(6):496-499.
41. Cheung, B., Lauder, I., Lau, C. and Kumana, C. Meta‐analysis of Large Randomized Controlled Trials to Evaluate the Impact of Statins on Cardiovascular Outcomes. British Journal of Clinical Pharmacology, 2004; 57(5):640-651.
42. Maggon, K. Best-selling Human Medicines 2002-2004. Drug Discovery Today, 2005; 10(11):739-742.
43. Vrecer, M., Turk, S., Drinovec, J. and Mrhar, A. Use of statins in primary and secondary prevention of coronary heart disease and ischemic stroke. Meta-analysis of randomized trials. International Journal of Clinical Pharmacology and Therapeutics, 2003; 41(12):567-577.
44. Maggo, M., Kennedy, M. and Clark, D. Clinical implications of pharmacogenetic variation on the effects of statins. Drug Safety, 2011; 34(1):11-19.
45. Davidson, M., Clark, J., Glass, L. and Kanumalla, A. Statin safety: an appraisal from the adverse event reporting system. The American Journal of Cardiology, 2006; 97(8):32-43.
46. Silva, M., Swanson, A., Gandhi, P. and Tataronis, G., et al. Statin-related adverse events: a meta-analysis. Clinical Therapeutics, 2006; 28(1):26-35.
47. Corsini, A., Bellosta, S., Baetta, R., Fumagalli, R., Paoletti, R. and Bernini, F. New insights into the pharmacodynamic and pharmacokinetic properties of statins. Pharmacology & Therapeutics, 1999; 84 (3):413-428.
48. Bolego, C., Baetta, R., Bellosta, S., Corsini, A. and Paoletti, R. Safety considerations for statins. Current Opinion in Lipidology, 2002; 13(6):637-644.
49. Kajinami, K., Brousseau, M., Ordovas, J. and Schaefer, E. CYP3A4 genotypes and plasma lipoprotein levels before and after treatment with atorvastatin in primary hypercholesterolemia. The American Journal of Cardiology, 2004; 93(1):104-107.
50. Salari, K. The dawning era of personalized medicine exposes a gap in medical education. PLoS Med, 2009; 6(8):e1000138.
51. Ormond, K. E., et al. Challenges in the clinical application of whole-genome sequencing. Lancet England, 2010; 375(9727):1749-1751.
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BEREWELA DA. The Pharmacogenetics of Cytochrome P-450 and its Effect on Drug Metabolism. JDDT [Internet]. 15Oct.2020 [cited 21Oct.2020];10(5-s):219-23. Available from: http://jddtonline.info/index.php/jddt/article/view/4473