FARMAKOGENOMIK: PENDEKATAN FARMAKOLOGI MENUJU PERSONALISED MEDICINE
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Variabilitas respon obat antar pasien merupakan salah satu penyebab morbiditas dan mortalitas pada pasien. Sebagian pasien dapat mengalami adverse drug reaction (ADR) maupun efek subterapeutik pada pemberian obat. Terdapat beberapa faktor yang berkontribusi terhadap hal tersebut, salah satunya adalah variabilitas genetik antar individu. Variabilitas genetik tersebut mendorong perkembangan ilmu farmakogenomik saat ini. Farmakogenomik adalah ilmu yang mempelajari bagaimana gen memengaruhi respon individu terhadap obat. Tujuan dikembangkannya farmakogenomik adalah untuk menghasilkan pengobatan yang lebih optimal. Beberapa gen telah dibuktikan memiliki keterkaitan terhadap respon obat, yang mana dapat mempengaruhi kadar obat di dalam darah (farmakokinetik) maupun efek obat secara langsung (farmakodinamik). Perubahan farmakokinetik dan farmakodinamik obat dapat berpotensi menyebabkan toksisitas maupun penurunan efektivitas suatu obat. Tulisan ini bertujuan untuk memaparkan ketersediaan informasi variasi genetik yang telah diketahui dapat mempengaruhi respon obat, sehingga dapat membantu meningkatkan ketepatan strategi farmakoterapi
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Referensi
Akhideno, P. et al. (2018) ‘Economic burden, impact, and consequence of adverse drug reactions among medical inpatients in clinical practice’, Journal of Clinical Sciences, 15(4), p. 186. doi: 10.4103/jcls.jcls_64_18.
Badan Pengawas Obat dan Makanan (2020) Cek Produk BPOM. Available at: https://cekbpom.pom.go.id/ (Accessed: 6 March 2020).
de Boer, A., van Hunsel, F. and Bast, A. (2015) ‘Adverse food-drug interactions’, Regulatory Toxicology and Pharmacology, 73(3), pp. 859–865. doi: 10.1016/j.yrtph.2015.10.009.
Brunton, L., Knollmann, B. and Randa, H.-D. (2017) Goodman and Gilman’s The Pharmacological Basis of Therapeutics. 14th edn. McGraw Hill Education.
Cacabelos, R., Cacabelos, N. and Carril, J. C. (2019) ‘The role of pharmacogenomics in adverse drug reactions’, Expert Review of Clinical Pharmacology, 12(5), pp. 407–442. doi: 10.1080/17512433.2019.1597706.
Carlson, R. W. et al. (2006) ‘HER2 testing in breast cancer: NCCN Task Force report and recommendations’, JNCCN Journal of the National Comprehensive Cancer Network, 4(SUPPL. 3).
Chan, S. L. et al. (2017) ‘Association and clinical utility of NAT2 in the prediction of isoniazid-induced liver injury in Singaporean patients’, PLoS ONE, 12(10), pp. 1–16. doi: 10.1371/journal.pone.0186200.
Chan, S. L. et al. (2019) ‘Economic burden of adverse drug reactions and potential for pharmacogenomic testing in Singaporean adults’, Pharmacogenomics Journal, 19(4), pp. 401–410. doi: 10.1038/s41397-018-0053-1.
Chen, M. et al. (2007) ‘N-acetyltransferase 2 slow acetylator genotype associated with adverse effects of sulfasalazine in the treatment of inflammatory bowel disease’, Canadian Journal of Gastroenterology, 21(3), pp. 155–158. doi: 10.1155/2007/976804.
Epstein, R. S. et al. (2010) ‘Warfarin Genotyping Reduces Hospitalization Rates. Results From the MM-WES (Medco-Mayo Warfarin Effectiveness Study)’, Journal of the American College of Cardiology, 55(25), pp. 2804–2812. doi: 10.1016/j.jacc.2010.03.009.
Fan, W. L. et al. (2017) ‘HLA Association with Drug-Induced Adverse Reactions’, Journal of Immunology Research, 2017. doi: 10.1155/2017/3186328.
Food and Drug Administration (2020) Table of Pharmacogenetic Associations.
Ginsberg, D. L. (2005) ‘Codeine intoxication associated with ultrarapid CYP 2D6 metabolism’, Primary Psychiatry, 12(4), pp. 26–27. doi: 10.1016/s1077-9108(08)70202-0.
Goldstein, D. B., Tate, S. K. and Sisodiya, S. M. (2003) ‘Pharmacogenetics goes genomic’, Nature Reviews Genetics, 4(12), pp. 937–947. doi: 10.1038/nrg1229.
Hirasawa, A. et al. (2013) ‘Polymorphisms in the UGT1A1 gene predict adverse effects of irinotecan in the treatment of gynecologic cancer in Japanese patients’, Journal of Human Genetics, 58(12), pp. 794–798. doi: 10.1038/jhg.2013.105.
Huang, Y. S. et al. (2002) ‘Polymorphism of the N-acetyltransferase 2 gene as a susceptibility risk factor for antituberculosis drug-induced hepatitis’, Hepatology, 35(4), pp. 883–889. doi: 10.1053/jhep.2002.32102.
Jiang, J. et al. (2016) ‘Association between SLCO1B1 − 521T > C and − 388A > G polymorphisms and risk of statin ‑ induced adverse drug reactions : A meta ‑ analysis’, SpringerPlus, (1), pp. 1–16. doi: 10.1186/s40064-016-2912-z.
Kalyani, S. S. A. and Srihitha, P. (2017) ‘An Epidemiological Study on Adverse Drug Reaction in Indian Population: Meta-Analysis’, International Journal of Pharmaceutical and Clinical Research, 9(10), pp. 654–659. Available at: http://impactfactor.org/PDF/IJPCR/9/IJPCR,Vol9,Issue10,Article4.pdf.
Katzung, B. G. (2018) Basic & Clinical Pharmacology. 14th edn. Edited by B. G. Katzung. San Fransisco: McGraw Hill Education.
Kim, S. et al. (2017) ‘Clinical pharmacogenetic testing and application: Laboratory medicine clinical practice guidelines’, Annals of Laboratory Medicine, 37(2), pp. 180–193. doi: 10.3343/alm.2017.37.2.180.
Lam, Y. W. F. (2019) Principles of Pharmacogenomics. Second Edi, Pharmacogenomics. Second Edi. Elsevier Inc. doi: 10.1016/b978-0-12-812626-4.00001-2.
Lea-Henry, T. N. et al. (2018) ‘Clinical pharmacokinetics in kidney disease: Fundamental principles’, Clinical Journal of the American Society of Nephrology, 13(7), pp. 1085–1095. doi: 10.2215/CJN.00340118.
Lee, S. Y. et al. (2016) ‘Effect of severe hypoalbuminemia on toxicity of high-dose melphalan and autologous stem cell transplantation in patients with AL amyloidosis’, Bone Marrow Transplantation, 51(10), pp. 1318–1322. doi: 10.1038/bmt.2016.132.
Li, Q. et al. (2014) ‘Influence of DPYD genetic polymorphisms on 5-fluorouracil toxicities in patients with colorectal cancer: A meta-analysis’, Gastroenterology Research and Practice, 2014. doi: 10.1155/2014/827989.
Liu, Y. et al. (2018) ‘Oxcarbazepine-Induced Cutaneous Adverse Reaction : a Meta-Analysis’, Pharmacogenomics.
Liu, Y. P. et al. (2015) ‘Association between thiopurine smethyltransferase polymorphisms and azathioprine-induced adverse drug reactions in patients with autoimmune diseases: A meta-analysis’, PLoS ONE, 10(12), pp. 1–14. doi: 10.1371/journal.pone.0144234.
Lloberas, N. et al. (2017) ‘The combination of CYP3A4∗22 and CYP3A5∗3 single-nucleotide polymorphisms determines tacrolimus dose requirement after kidney transplantation’, Pharmacogenetics and Genomics, 27(9), pp. 313–322. doi: 10.1097/FPC.0000000000000296.
Lui, C. T. and Fung, H. T. (2010) ‘A case of tolterodine poisoning’, Hong Kong Journal of Emergency Medicine, 17(2), pp. 168–172. doi: 10.1177/102490791001700211.
Madadi, P. et al. (2007) ‘Safety of codeine during breastfeeding: Fatal morphine poisoning in the breastfed neonate of a mother prescribed codeine’, Canadian Family Physician, 53(1), pp. 33–35.
Manikandan, P. and Nagini, S. (2017) ‘Cytochrome P450 Structure, Function and Clinical Significance: A Review’, Current Drug Targets, 19(1), pp. 38–54. doi: 10.2174/1389450118666170125144557.
Manosuthi, W. et al. (2014) ‘CYP2B6 haplotype and biological factors responsible for hepatotoxicity in HIV-infected patients receiving efavirenz-based antiretroviral therapy’, International Journal of Antimicrobial Agents, 43(3), pp. 292–296. doi: 10.1016/j.ijantimicag.2013.10.022.
Misasi, S. et al. (2016) ‘VKORC1 and CYP2C9 polymorphisms related to adverse events in case-control cohort of anticoagulated patients’, Medicine (United States), 95(52), pp. 1–7. doi: 10.1097/MD.0000000000005451.
Moore, N., Pollack, C. and Butkerait, P. (2015) ‘Adverse drug reactions and drug–drug interactions with over-the-counter NSAIDs’, Therapeutics and Clinical Risk Management, 11, pp. 1061–1075. doi: 10.2147/TCRM.S79135.
Nahar, R. et al. (2013) ‘Variability in CYP2C9 allele frequency: A pilot study of its predicted impact on warfarin response among healthy South and North Indians’, Pharmacological Reports, 65(1), pp. 187–194. doi: 10.1016/S1734-1140(13)70977-0.
Orliaguet, G. et al. (2015) ‘A case of respiratory depression in a child with ultrarapid CYP2D6 metabolism after tramadol’, Pediatrics, 135(3), pp. e753–e755. doi: 10.1542/peds.2014-2673.
van der Padt, A., van Schaik, R. H. N. and Sonneveld, P. (2006) ‘Acute dystonic reaction to metoclopramide in patients carrying homozygous cytochrome P450 2D6 genetic polymorphisms’, Netherlands Journal of Medicine, 64(5), pp. 160–162.
Parham, L. R. et al. (2016) ‘Comprehensive genome-wide evaluation of lapatinib-induced liver injury yields a single genetic signal centered on known risk allele HLA-DRB1∗07:01’, Pharmacogenomics Journal, 16(2), pp. 180–185. doi: 10.1038/tpj.2015.40.
Pilotto, A. et al. (2007) ‘Genetic Susceptibility to Nonsteroidal Anti-Inflammatory Drug-Related Gastroduodenal Bleeding: Role of Cytochrome P450 2C9 Polymorphisms’, Gastroenterology, 133(2), pp. 465–471. doi: 10.1053/j.gastro.2007.05.025.
Prows, C. A. et al. (2014) ‘Codeine-related adverse drug reactions in children following tonsillectomy: A prospective study’, Laryngoscope, 124(5), pp. 1242–1250. doi: 10.1002/lary.24455.
Di Sanzo, M. et al. (2017) ‘Clinical Applications of Personalized Medicine: A New Paradigm and Challenge’, Current Pharmaceutical Biotechnology, 18(3), pp. 194–203. doi: 10.2174/1389201018666170224105600.
Shah, V. (2014) ‘New allergy drug excipient allergy’, Clinical and Translational Allergy, 4(S3), p. P134. doi: 10.1186/2045-7022-4-s3-p134.
Shibata, T. et al. (2014) ‘Association between severe toxicity of nilotinib and UGT1A1 polymorphisms in Japanese patients with chronic myelogenous leukemia’, International Journal of Clinical Oncology, 19(2), pp. 391–396. doi: 10.1007/s10147-013-0562-5.
Si, D. et al. (2014) ‘Association of common polymorphisms in b1-adrenergic receptor with antihypertensive response to carvedilol’, Journal of Cardiovascular Pharmacology, 64(4), pp. 306–309. doi: 10.1097/FJC.0000000000000119.
Siddoway, L. A. et al. (1987) ‘Polymorphism of propafenone metabolism and disposition in man: Clinical and pharmacokinetic consequences’, Circulation, 75(4), pp. 785–791. doi: 10.1161/01.CIR.75.4.785.
Siew, H. G. et al. (2007) ‘Impact of CYP2D6 genetic polymorphism on tramadol pharmacokinetics and pharmacodynamics’, Molecular Diagnosis and Therapy, 11(3), pp. 171–181. doi: 10.1007/bf03256239.
Soejima, M. et al. (2007) ‘Research article Association of the diplotype configuration at the N -acetyltransferase 2 gene with adverse events with co-trimoxazole in Japanese patients with systemic lupus erythematosus’, Arthritis Research & Therapy, 9(2). doi: https://arthritis-research.biomedcentral.com/articles/10.1186/ar2134.
Sotsuka, T. et al. (2011) ‘Association of isoniazid-metabolizing enzyme genotypes and isoniazid-induced hepatotoxicity in tuberculosis patients’, In Vivo, 25(5), pp. 803–812.
Suzumura, T. et al. (2012) ‘Reduced CYP2D6 function is associated with gefitinib-induced rash in patients with non-small cell lung cancer’, BMC Cancer, 12(1), p. 1. doi: 10.1186/1471-2407-12-568.
T P, A. (2009) ‘Pharmacogenomics: The Right Drug to the Right Person’, Journal of Clinical Medicine Research, 1(4), pp. 191–194. doi: 10.4021/jocmr2009.08.1255.
Takimoto, T. et al. (2013) ‘Polymorphisms of CYP2D6 gene and gefitinib-induced hepatotoxicity’, Clinical Lung Cancer, 14(5), pp. 502–507. doi: 10.1016/j.cllc.2013.03.003.
Tanaka, E. et al. (2002) ‘Adverse effects of sulfasalazine in patients with rheumatoid arthritis are associated with diplotype configuration at the N-acetyltransferase 2 gene’, Journal of Rheumatology, 29(12), pp. 2492–2499.
Vasudev, K. et al. (2017) ‘Genetic Determinants of Clozapine-Induced Metabolic Side Effects’, Canadian Journal of Psychiatry, 62(2), pp. 138–149. doi: 10.1177/0706743716670128.
Wee Chua, E., Harger, S. P. and Kennedy, M. A. (2019) ‘Metoclopramide-induced acute dystonic reactions may be associated with the CYP2D6 poor metaboliser status and pregnancy-related hormonal changes’, Frontiers in Pharmacology, 10(JULY), pp. 2–6. doi: 10.3389/fphar.2019.00931.
Weinshilboum, R. M. and Wang, L. (2017) ‘Pharmacogenomics: Precision Medicine and Drug Response’, Mayo Clinic Proceedings, 92(11), pp. 1711–1722. doi: 10.1016/j.mayocp.2017.09.001.
Westervelt, P. et al. (2014) ‘Drug–gene interactions: Inherent variability in drug maintenance dose requirements’, P and T, 39(9), pp. 630–637.
Xu, C. et al. (2016) ‘UGT1A1 gene polymorphism is associated with toxicity and clinical efficacy of irinotecan-based chemotherapy in patients with advanced colorectal cancer’, Cancer Chemotherapy and Pharmacology, 78(1), pp. 119–130. doi: 10.1007/s00280-016-3057-z.
Xu, C. F. et al. (2010) ‘Pazopanib-induced hyperbilirubinemia is associated with Gilbert’s syndrome UGT1A1 polymorphism’, British Journal of Cancer, 102(9), pp. 1371–1377. doi: 10.1038/sj.bjc.6605653.
Xu, C. F. et al. (2016) ‘HLA-B∗57:01 confers susceptibility to pazopanib-associated liver injury in patients with cancer’, Clinical Cancer Research, 22(6), pp. 1371–1377. doi: 10.1158/1078-0432.CCR-15-2044.
Yee, S. W. et al. (2018) ‘Influence of Transporter Polymorphisms on Drug Disposition and Response: A Perspective From the International Transporter Consortium’, Clinical Pharmacology & Therapeutics, 104(5), pp. 803–817. doi: 10.1002/cpt.1098.
Yu, B. N. et al. (2003) ‘Pharmacokinetics of citalopram in relation to genetic polymorphism of CYP2C19’, Drug Metabolism and Disposition, 31(10), pp. 1255–1259. doi: 10.1124/dmd.31.10.1255.
Zielin, E. (1998) ‘The arylamine N-acetyltransferase ( NAT2 ) polymorphism and the risk of adverse reactions to co-trimoxazole in children’, pp. 779–785. doi: https://doi.org/10.1007/s002280050551.