Pharmacogenomics: an opportunity for safer and efficient pharmacotherapy
DOI:
https://doi.org/10.33448/rsd-v11i17.38884Keywords:
Pharmacogenetics; Pharmacogenomics; Adverse drug reactions; Genetic polymorphisms; Personalized medicine.Abstract
Responses to drugs are influenced by multiple factors, including health status, environmental influences, and genetic characteristics. The bioavailability of a drug can vary widely among individuals with a similar weight under the same drug dosage, which might result in toxicity and adverse drug reactions (ADRs). Genetic polymorphisms are known causes of interindividual differences in disease risk and treatment response in humans. In fact, a relevant number of associations between human genetic variants and predisposition to adverse events were described for diverse kinds of drug interactions, involving hundreds of proteins like receptors, transporters, and metabolizing enzymes. In this way, Pharmacogenetics and Pharmacogenomics emerged aiming to determine the genetic component responsible for drug response. A particular attention is showed if a treatment benefits (or harms) a particular subgroup, considering the interaction between treatment and genetic background. In this scenario, researchers have focused on better understanding personalized medicine, which holds the potential to maximize drug efficiency and minimize toxic effects. This review aims to introduce some principles, perspectives, and clinical applications of pharmacogenetics, emphasizing important findings and clinical applications that may contribute to therapeutical improvement.
References
Agundez, J. A. G., & Garcia-Martin, E. (2022). Editorial: Insights in Pharmacogenetics and Pharmacogenomics: 2021. Front Pharmacol, 13, 907131. doi:10.3389/fphar.2022.907131
Aithal, G. P., Day, C. P., Kesteven, P. J., & Daly, A. K. (1999). Association of polymorphisms in the cytochrome P450 CYP2C9 with warfarin dose requirement and risk of bleeding complications. Lancet, 353(9154), 717-719. doi:10.1016/S0140-6736(98)04474-2
Anastassopoulou, C., Gkizarioti, Z., Patrinos, G. P., & Tsakris, A. (2020). Human genetic factors associated with susceptibility to SARS-CoV-2 infection and COVID-19 disease severity. Hum Genomics, 14(1), 40. doi:10.1186/s40246-020-00290-4
Annett, S. (2021). Pharmaceutical drug development: high drug prices and the hidden role of public funding. Biol Futur, 72(2), 129-138. doi:10.1007/s42977-020-00025-5
Becker, M. L., & Leeder, J. S. (2010). Identifying genomic and developmental causes of adverse drug reactions in children. Pharmacogenomics, 11(11), 1591-1602. doi:10.2217/pgs.10.146
Bienfait, K., Chhibber, A., Marshall, J. C., Armstrong, M., Cox, C., Shaw, P. M., & Paulding, C. (2022). Current challenges and opportunities for pharmacogenomics: perspective of the Industry Pharmacogenomics Working Group (I-PWG). Hum Genet, 141(6), 1165-1173. doi:10.1007/s00439-021-02282-3
Cacabelos, R., Cacabelos, N., & Carril, J. C. (2019). The role of pharmacogenomics in adverse drug reactions. Expert Rev Clin Pharmacol, 12(5), 407-442. doi:10.1080/17512433.2019.1597706
Chen, Y., Zhou, D., Tang, W., Zhou, W., Al-Huniti, N., & Masson, E. (2018). Physiologically Based Pharmacokinetic Modeling to Evaluate the Systemic Exposure of Gefitinib in CYP2D6 Ultrarapid Metabolizers and Extensive Metabolizers. J Clin Pharmacol, 58(4), 485-493. doi:10.1002/jcph.1036
Chowbay, B., Cumaraswamy, S., Cheung, Y. B., Zhou, Q., & Lee, E. J. (2003). Genetic polymorphisms in MDR1 and CYP3A4 genes in Asians and the influence of MDR1 haplotypes on cyclosporin disposition in heart transplant recipients. Pharmacogenetics, 13(2), 89-95. doi:10.1097/00008571-200302000-00005
Cohen, M., Quintner, J., & van Rysewyk, S. (2018). Reconsidering the International Association for the Study of Pain definition of pain. Pain Rep, 3(2), e634. doi:10.1097/PR9.0000000000000634
Cohen, S. P., Vase, L., & Hooten, W. M. (2021). Chronic pain: an update on burden, best practices, and new advances. Lancet, 397(10289), 2082-2097. doi:10.1016/S0140-6736(21)00393-7
Collins, K. S., Raviele, A. L. J., Elchynski, A. L., Woodcock, A. M., Zhao, Y., Cooper-DeHoff, R. M., & Eadon, M. T. (2020). Genotype-Guided Hydralazine Therapy. Am J Nephrol, 51(10), 764-776. doi:10.1159/000510433
Cronin, P., Ryan, F., & Coughlan, M. (2008). Undertaking a literature review: a step-by-step approach. Br J Nurs, 17(1), 38-43. doi:10.12968/bjon.2008.17.1.28059
Destenaves, B., & Thomas, F. (2000). New advances in pharmacogenomics. Curr Opin Chem Biol, 4(4), 440-444. doi:10.1016/s1367-5931(00)00101-0
Edwards, I. R., & Aronson, J. K. (2000). Adverse drug reactions: definitions, diagnosis, and management. Lancet, 356(9237), 1255-1259. doi:10.1016/S0140-6736(00)02799-9
Evans, W. E., & Relling, M. V. (1999). Pharmacogenomics: translating functional genomics into rational therapeutics. Science, 286(5439), 487-491. doi:10.1126/science.286.5439.487
FDA. Table of Pharmacogenomic Biomarkers in Drug Labeling [Internet].
Feld, J. J., & Hoofnagle, J. H. (2005). Mechanism of action of interferon and ribavirin in treatment of hepatitis C. Nature, 436(7053), 967-972. doi:10.1038/nature04082
Fillingim, R. B., Wallace, M. R., Herbstman, D. M., Ribeiro-Dasilva, M., & Staud, R. (2008). Genetic contributions to pain: a review of findings in humans. Oral Dis, 14(8), 673-682. doi:10.1111/j.1601-0825.2008.01458.x
Fontes, F. L., de Araujo, L. F., Coutinho, L. G., Leib, S. L., & Agnez-Lima, L. F. (2015). Genetic polymorphisms associated with the inflammatory response in bacterial meningitis. BMC Med Genet, 16, 70. doi:10.1186/s12881-015-0218-6
Frudakis, T. N., Thomas, M. J., Ginjupalli, S. N., Handelin, B., Gabriel, R., & Gomez, H. J. (2007). CYP2D6*4 polymorphism is associated with statin-induced muscle effects. Pharmacogenet Genomics, 17(9), 695-707. doi:10.1097/FPC.0b013e328012d0a9
Fukuda, T., Nishida, Y., Imaoka, S., Hiroi, T., Naohara, M., Funae, Y., & Azuma, J. (2000). The decreased in vivo clearance of CYP2D6 substrates by CYP2D6*10 might be caused not only by the low-expression but also by low affinity of CYP2D6. Arch Biochem Biophys, 380(2), 303-308. doi:10.1006/abbi.2000.1936
Gardiner, S. J., & Begg, E. J. (2006). Pharmacogenetics, drug-metabolizing enzymes, and clinical practice. Pharmacol Rev, 58(3), 521-590. doi:10.1124/pr.58.3.6
Ge, D., Fellay, J., Thompson, A. J., Simon, J. S., Shianna, K. V., Urban, T. J., . . . Goldstein, D. B. (2009). Genetic variation in IL28B predicts hepatitis C treatment-induced viral clearance. Nature, 461(7262), 399-401. doi:10.1038/nature08309
Genomes Project, C., Abecasis, G. R., Altshuler, D., Auton, A., Brooks, L. D., Durbin, R. M., . . . McVean, G. A. (2010). A map of human genome variation from population-scale sequencing. Nature, 467(7319), 1061-1073. doi:10.1038/nature09534
Gjerdevik, M., Gjessing, H. K., Romanowska, J., Haaland, O. A., Jugessur, A., Czajkowski, N. O., & Lie, R. T. (2020). Design efficiency in genetic association studies. Stat Med, 39(9), 1292-1310. doi:10.1002/sim.8476
Goldspiel, B. R., Flegel, W. A., DiPatrizio, G., Sissung, T., Adams, S. D., Penzak, S. R., . . . McKeeby, J. W. (2014). Integrating pharmacogenetic information and clinical decision support into the electronic health record. J Am Med Inform Assoc, 21(3), 522-528. doi:10.1136/amiajnl-2013-001873
Grasmader, K., Verwohlt, P. L., Rietschel, M., Dragicevic, A., Muller, M., Hiemke, C., . . . Rao, M. L. (2004). Impact of polymorphisms of cytochrome-P450 isoenzymes 2C9, 2C19 and 2D6 on plasma concentrations and clinical effects of antidepressants in a naturalistic clinical setting. Eur J Clin Pharmacol, 60(5), 329-336. doi:10.1007/s00228-004-0766-8
Gupta, R., Srivastava, D., Sahu, M., Tiwari, S., Ambasta, R. K., & Kumar, P. (2021). Artificial intelligence to deep learning: machine intelligence approach for drug discovery. Mol Divers, 25(3), 1315-1360. doi:10.1007/s11030-021-10217-3
Hecht, J. R., Douillard, J. Y., Schwartzberg, L., Grothey, A., Kopetz, S., Rong, A., . . . Sidhu, R. (2015). Extended RAS analysis for anti-epidermal growth factor therapy in patients with metastatic colorectal cancer. Cancer Treat Rev, 41(8), 653-659. doi:10.1016/j.ctrv.2015.05.008
Hetherington, S., McGuirk, S., Powell, G., Cutrell, A., Naderer, O., Spreen, B., . . . Steel, H. (2001). Hypersensitivity reactions during therapy with the nucleoside reverse transcriptase inhibitor abacavir. Clin Ther, 23(10), 1603-1614. doi:10.1016/s0149-2918(01)80132-6
Ingelman-Sundberg, M. (2001). Pharmacogenetics: an opportunity for a safer and more efficient pharmacotherapy. J Intern Med, 250(3), 186-200. doi:10.1046/j.1365-2796.2001.00879.x
Ingelman-Sundberg, M. (2004). Human drug metabolising cytochrome P450 enzymes: properties and polymorphisms. Naunyn Schmiedebergs Arch Pharmacol, 369(1), 89-104. doi:10.1007/s00210-003-0819-z
International Warfarin Pharmacogenetics, C., Klein, T. E., Altman, R. B., Eriksson, N., Gage, B. F., Kimmel, S. E., . . . Johnson, J. A. (2009). Estimation of the warfarin dose with clinical and pharmacogenetic data. N Engl J Med, 360(8), 753-764. doi:10.1056/NEJMoa0809329
Jaja, C., Burke, W., Thummel, K., Edwards, K., & Veenstra, D. L. (2008). Cytochrome p450 enzyme polymorphism frequency in indigenous and native american populations: a systematic review. Community Genet, 11(3), 141-149. doi:10.1159/000113876
Johnson, J. A., Burkley, B. M., Langaee, T. Y., Clare-Salzler, M. J., Klein, T. E., & Altman, R. B. (2012). Implementing personalized medicine: development of a cost-effective customized pharmacogenetics genotyping array. Clin Pharmacol Ther, 92(4), 437-439. doi:10.1038/clpt.2012.125
Johnson, J. A., & Evans, W. E. (2002). Molecular diagnostics as a predictive tool: genetics of drug efficacy and toxicity. Trends Mol Med, 8(6), 300-305. doi:10.1016/s1471-4914(02)02354-7
Kamatani, Y., & Nakamura, Y. (2021). Genetic variations in medical research in the past, at present and in the future. Proc Jpn Acad Ser B Phys Biol Sci, 97(6), 324-335. doi:10.2183/pjab.97.018
Karki, R., Pandya, D., Elston, R. C., & Ferlini, C. (2015). Defining "mutation" and "polymorphism" in the era of personal genomics. BMC Med Genomics, 8, 37. doi:10.1186/s12920-015-0115-z
Kauf, T. L., Farkouh, R. A., Earnshaw, S. R., Watson, M. E., Maroudas, P., & Chambers, M. G. (2010). Economic efficiency of genetic screening to inform the use of abacavir sulfate in the treatment of HIV. Pharmacoeconomics, 28(11), 1025-1039. doi:10.2165/11535540-000000000-00000
Krau, S. D. (2013). Cytochrome p450, part 1: what nurses really need to know. Nurs Clin North Am, 48(4), 671-680. doi:10.1016/j.cnur.2013.09.002
Kristyanto, H., & Utomo, A. R. (2010). Pharmacogenetic application in personalized cancer treatment. Acta Med Indones, 42(2), 109-115.
Kuzgun, G., Basaran, R., Arioglu Inan, E., & Can Eke, B. (2020). Effects of insulin treatment on hepatic CYP1A1 and CYP2E1 activities and lipid peroxidation levels in streptozotocin-induced diabetic rats. J Diabetes Metab Disord, 19(2), 1157-1164. doi:10.1007/s40200-020-00616-y
Lazarou, J., Pomeranz, B. H., & Corey, P. N. (1998). Incidence of adverse drug reactions in hospitalized patients: a meta-analysis of prospective studies. JAMA, 279(15), 1200-1205. doi:10.1001/jama.279.15.1200
Lehmann, H., & Ryan, E. (1956). The familial incidence of low pseudocholinesterase level. Lancet, 271(6934), 124. doi:10.1016/s0140-6736(56)90869-8
Ma, Q., & Lu, A. Y. (2011). Pharmacogenetics, pharmacogenomics, and individualized medicine. Pharmacol Rev, 63(2), 437-459. doi:10.1124/pr.110.003533
Maksimovic, V., Pavlovic-Popovic, Z., Vukmirovic, S., Cvejic, J., Mooranian, A., Al-Salami, H., . . . Golocorbin-Kon, S. (2020). Molecular mechanism of action and pharmacokinetic properties of methotrexate. Mol Biol Rep, 47(6), 4699-4708. doi:10.1007/s11033-020-05481-9
Mallal, S., Phillips, E., Carosi, G., Molina, J. M., Workman, C., Tomazic, J., . . . Team, P.-S. (2008). HLA-B*5701 screening for hypersensitivity to abacavir. N Engl J Med, 358(6), 568-579. doi:10.1056/NEJMoa0706135
Mulder, T. A. M., van Eerden, R. A. G., de With, M., Elens, L., Hesselink, D. A., Matic, M., . . . van Schaik, R. H. N. (2021). CYP3A4( *)22 Genotyping in Clinical Practice: Ready for Implementation? Front Genet, 12, 711943. doi:10.3389/fgene.2021.711943
Nebert, D. W., & Russell, D. W. (2002). Clinical importance of the cytochromes P450. Lancet, 360(9340), 1155-1162. doi:10.1016/S0140-6736(02)11203-7
Nebert, D. W., Zhang, G., & Vesell, E. S. (2008). From human genetics and genomics to pharmacogenetics and pharmacogenomics: past lessons, future directions. Drug Metab Rev, 40(2), 187-224. doi:10.1080/03602530801952864
Noguchi, K., Katayama, K., & Sugimoto, Y. (2014). Human ABC transporter ABCG2/BCRP expression in chemoresistance: basic and clinical perspectives for molecular cancer therapeutics. Pharmgenomics Pers Med, 7, 53-64. doi:10.2147/PGPM.S38295
Norton, R. M. (2001). Clinical pharmacogenomics: applications in pharmaceutical R&D. Drug Discov Today, 6(4), 180-185. doi:10.1016/s1359-6446(00)01648-2
O'Rielly, D. D., & Rahman, P. (2015). Genetic, Epigenetic and Pharmacogenetic Aspects of Psoriasis and Psoriatic Arthritis. Rheum Dis Clin North Am, 41(4), 623-642. doi:10.1016/j.rdc.2015.07.002
Patel, J., Abd, T., Blumenthal, R. S., Nasir, K., & Superko, H. R. (2014). Genetics and personalized medicine--a role in statin therapy? Curr Atheroscler Rep, 16(1), 384. doi:10.1007/s11883-013-0384-y
Peters, J. L., Cooper, C., & Buchanan, J. (2015). Evidence used in model-based economic evaluations for evaluating pharmacogenetic and pharmacogenomic tests: a systematic review protocol. BMJ Open, 5(11), e008465. doi:10.1136/bmjopen-2015-008465
Qi, G., Zhang, J., Han, C., Zhou, Y., Li, D., & Ma, P. (2021). Genetic landscape of 125 pharmacogenes in Chinese from the Chinese Millionome Database. Sci Rep, 11(1), 19222. doi:10.1038/s41598-021-98877-x
Racoosin, J. A., Roberson, D. W., Pacanowski, M. A., & Nielsen, D. R. (2013). New evidence about an old drug--risk with codeine after adenotonsillectomy. N Engl J Med, 368(23), 2155-2157. doi:10.1056/NEJMp1302454
Roses, A. D. (2004). Pharmacogenetics and drug development: the path to safer and more effective drugs. Nat Rev Genet, 5(9), 645-656. doi:10.1038/nrg1432
Ross, S., Anand, S. S., Joseph, P., & Pare, G. (2012). Promises and challenges of pharmacogenetics: an overview of study design, methodological and statistical issues. JRSM Cardiovasc Dis, 1(1). doi:10.1258/cvd.2012.012001
Sabaawy, H. E. (2013). Genetic Heterogeneity and Clonal Evolution of Tumor Cells and their Impact on Precision Cancer Medicine. J Leuk (Los Angel), 1(4), 1000124. doi:10.4172/2329-6917.1000124
Sadhasivam, S., Chidambaran, V., Olbrecht, V. A., Esslinger, H. R., Zhang, K., Zhang, X., & Martin, L. J. (2014). Genetics of pain perception, COMT and postoperative pain management in children. Pharmacogenomics, 15(3), 277-284. doi:10.2217/pgs.13.248
Sagar, M., Bertilsson, L., Stridsberg, M., Kjellin, A., Mardh, S., & Seensalu, R. (2000). Omeprazole and CYP2C19 polymorphism: effects of long-term treatment on gastrin, pepsinogen I, and chromogranin A in patients with acid related disorders. Aliment Pharmacol Ther, 14(11), 1495-1502. doi:10.1046/j.1365-2036.2000.00835.x
Sasson, A. N., Ananthakrishnan, A. N., & Raman, M. (2021). Diet in Treatment of Inflammatory Bowel Diseases. Clin Gastroenterol Hepatol, 19(3), 425-435 e423. doi:10.1016/j.cgh.2019.11.054
Schafer, A. J., & Hawkins, J. R. (1998). DNA variation and the future of human genetics. Nat Biotechnol, 16(1), 33-39. doi:10.1038/nbt0198-33
Schnappauf, O. (2020). [Genetic diagnostics of autoinflammatory diseases]. Z Rheumatol, 79(7), 611-623. doi:10.1007/s00393-020-00847-7
Shojaei, S., Gardaneh, M., & Rahimi Shamabadi, A. (2012). Target points in trastuzumab resistance. Int J Breast Cancer, 2012, 761917. doi:10.1155/2012/761917
Somogyi, A. A., Barratt, D. T., & Coller, J. K. (2007). Pharmacogenetics of opioids. Clin Pharmacol Ther, 81(3), 429-444. doi:10.1038/sj.clpt.6100095
Stamp, L. K., Chapman, P. T., O'Donnell, J. L., Zhang, M., James, J., Frampton, C., . . . Roberts, R. L. (2010). Polymorphisms within the folate pathway predict folate concentrations but are not associated with disease activity in rheumatoid arthritis patients on methotrexate. Pharmacogenet Genomics, 20(6), 367-376. doi:10.1097/FPC.0b013e3283398a71
Stegemann, S. (2016). The future of pharmaceutical manufacturing in the context of the scientific, social, technological and economic evolution. Eur J Pharm Sci, 90, 8-13. doi:10.1016/j.ejps.2015.11.003
Talseth-Palmer, B. A., & Scott, R. J. (2011). Genetic variation and its role in malignancy. Int J Biomed Sci, 7(3), 158-171.
Tekola-Ayele, F., & Rotimi, C. N. (2015). Translational Genomics in Low- and Middle-Income Countries: Opportunities and Challenges. Public Health Genomics, 18(4), 242-247. doi:10.1159/000433518
Thomas, L., Raju, A. P., Chaithra, M, S. S., Varma, M., Saravu, K., . . . Rao, M. (2022). Influence of N-acetyltransferase 2 (NAT2) genotype/single nucleotide polymorphisms on clearance of isoniazid in tuberculosis patients: a systematic review of population pharmacokinetic models. Eur J Clin Pharmacol, 78(10), 1535-1553. doi:10.1007/s00228-022-03362-7
Thong, B. Y., Vultaggio, A., Rerkpattanapipat, T., & Schrijvers, R. (2021). Prevention of Drug Hypersensitivity Reactions: Prescreening and Premedication. J Allergy Clin Immunol Pract, 9(8), 2958-2966. doi:10.1016/j.jaip.2021.04.006
Thummel, K. E., & Wilkinson, G. R. (1998). In vitro and in vivo drug interactions involving human CYP3A. Annu Rev Pharmacol Toxicol, 38, 389-430. doi:10.1146/annurev.pharmtox.38.1.389
Tippenhauer, K., Philips, M., Largiader, C. R., Sariyar, M., & Burkle, T. (2020). Integrating Pharmacogenetic Decision Support into a Clinical Information System. Stud Health Technol Inform, 270, 618-622. doi:10.3233/SHTI200234
van der Wouden, C. H., Marck, H., Guchelaar, H. J., Swen, J. J., & van den Hout, W. B. (2022). Cost-Effectiveness of Pharmacogenomics-Guided Prescribing to Prevent Gene-Drug-Related Deaths: A Decision-Analytic Model. Front Pharmacol, 13, 918493. doi:10.3389/fphar.2022.918493
Veluchamy, A., Hebert, H. L., van Zuydam, N. R., Pearson, E. R., Campbell, A., Hayward, C., . . . Smith, B. H. (2021). Association of Genetic Variant at Chromosome 12q23.1 With Neuropathic Pain Susceptibility. JAMA Netw Open, 4(12), e2136560. doi:10.1001/jamanetworkopen.2021.36560
Verbelen, M., Weale, M. E., & Lewis, C. M. (2017). Cost-effectiveness of pharmacogenetic-guided treatment: are we there yet? Pharmacogenomics J, 17(5), 395-402. doi:10.1038/tpj.2017.21
Wang, B., Yang, L. P., Zhang, X. Z., Huang, S. Q., Bartlam, M., & Zhou, S. F. (2009). New insights into the structural characteristics and functional relevance of the human cytochrome P450 2D6 enzyme. Drug Metab Rev, 41(4), 573-643. doi:10.1080/03602530903118729
Wang, D., Guo, Y., Wrighton, S. A., Cooke, G. E., & Sadee, W. (2011). Intronic polymorphism in CYP3A4 affects hepatic expression and response to statin drugs. Pharmacogenomics J, 11(4), 274-286. doi:10.1038/tpj.2010.28
Waring, R. H. (2020). Cytochrome P450: genotype to phenotype. Xenobiotica, 50(1), 9-18. doi:10.1080/00498254.2019.1648911
Weng, Y., Li, C., Yang, T., Hu, B., Zhang, M., Guo, S., . . . Huang, Y. (2020). The challenge and prospect of mRNA therapeutics landscape. Biotechnol Adv, 40, 107534. doi:10.1016/j.biotechadv.2020.107534
Wessels, J. A., Kooloos, W. M., De Jonge, R., De Vries-Bouwstra, J. K., Allaart, C. F., Linssen, A., . . . Guchelaar, H. J. (2006). Relationship between genetic variants in the adenosine pathway and outcome of methotrexate treatment in patients with recent-onset rheumatoid arthritis. Arthritis Rheum, 54(9), 2830-2839. doi:10.1002/art.22032
Wilkinson, G. R. (2005). Drug metabolism and variability among patients in drug response. N Engl J Med, 352(21), 2211-2221. doi:10.1056/NEJMra032424
Wu, Y., Pan, L., Chen, Z., Zheng, Y., Diao, X., & Zhong, D. (2021). Metabolite Identification in the Preclinical and Clinical Phase of Drug Development. Curr Drug Metab, 22(11), 838-857. doi:10.2174/1389200222666211006104502
Yamamoto, P. A., Conchon Costa, A. C., Lauretti, G. R., & de Moraes, N. V. (2019). Pharmacogenomics in chronic pain therapy: from disease to treatment and challenges for clinical practice. Pharmacogenomics, 20(13), 971-982. doi:10.2217/pgs-2019-0066
Yang, S. C., Chen, C. B., Lin, M. Y., Zhang, Z. Y., Jia, X. Y., Huang, M., . . . Chung, W. H. (2021). Genetics of Severe Cutaneous Adverse Reactions. Front Med (Lausanne), 8, 652091. doi:10.3389/fmed.2021.652091
Zhao, M., Ma, J., Li, M., Zhang, Y., Jiang, B., Zhao, X., . . . Qin, S. (2021). Cytochrome P450 Enzymes and Drug Metabolism in Humans. Int J Mol Sci, 22(23). doi:10.3390/ijms222312808
Zhao, W., & Meng, H. (2022). Effects of genetic polymorphism of drug-metabolizing enzymes on the plasma concentrations of antiepileptic drugs in Chinese population. Bioengineered, 13(3), 7709-7745. doi:10.1080/21655979.2022.2036916
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