Problems of Social Hygiene, Public Health and History of MedicineProblems of Social Hygiene, Public Health and History of Medicine0869-866X2412-2106Joint-Stock Company Chicot145010.32687/0869-866X-2024-32-2-173-179НеопределенThe pharmacogenetics as integral part of personalized medicine: problems and prospectsAmlaevK Rkum672002@mail.ruKhripunovaA Afktcz2007@yandex.ruMaksimenkoL Lllmaks@yandex.ruKhripunovaI Gigh2011@yandex.ruMaksimenkoE Vkatimax@yandex.ruStepanyanT Ostepanyan.tamara@list.ruThe Federal State Budget Educational Institution of Higher Education “The Stavropol State Medical University” of Minzdrav of Russia, 355017, Stavropol, Russia180420243222104202521042025Copyright © 2025,2025<p>The article considers issues of implementation into clinical practice the principles of 5P medicine in its part of individualization of therapeutic tactics considering genetic characteristics of patients. The analysis of studies concerning influence of allelic variations on metabolism, safety and tolerance of the most often prescribed medicinal preparations was implemented. The main assumptions of pharmacogenomics were considered. Despite broad perspective of applying obtained data in clinical practice, there are a number of unresolved problems related to accessibility of genetic testing to population, ambiguity of approaches to interpretation of obtaining results, ethical issues and legal regulation.</p>pharmacogenomicshealth carepersonalized medicinegenetic variationsmedicinal therapyфармакогеномиказдравоохранениеперсонализированная медицинагенетические вариантымедикаментозная терапия[Principi N., Petropulacos K., Esposito S. Impact of Pharmacogenomics in Clinical Practice. Pharmaceuticals (Basel). 2023;16(11):1596. doi: 10.3390/ph16111596][Shaaban S., Ji Y. Pharmacogenomics and health disparities, are we helping? Front. Genet. 2023;14:1099541. doi: 10.3389/fgene.2023.1099541][Thummel K. E., Lin Y. S. Sources of interindividual variability. In: Enzyme Kinetics in Drug Metabolism; Humana Press: Totowa, NJ, USA, 2014. P. 363–415.][Joy M. S. Impact of glomerular kidney diseases on the clearance of drugs. J. Clin. Pharmacol. 2012;52(Suppl. S1):23S–34S.][Weersink R. A., Bouma M., Burger D. M., Drenth J. P., Hunfeld N. G., Kranenborg M., Monster-Simons M. H., van Putten S. A., Metselaar H. J., Taxis K. Evaluating the safety and dosing of drugs in patients with liver cirrhosis by literature review and expert opinion. BMJ Open 2016;6:e012991.][Ruggiero A., Ariano A., Triarico S., Capozza M. A., Ferrara P., Attina G. Neonatal pharmacology and clinical implications. Drugs Context. 2019;8:212608.][Porta A., Esposito S., Menson E., Spyridis N., Tsolia M., Sharland M., Principi N. Off-label antibiotic use in children in three European countries. Eur. J. Clin. Pharmacol. 2010;66:919–27.][Kalow W., Tang B. K., Endrenyi L. Hypothesis: Comparisons of inter- and intra-individual variations can substitute for twin studies in drug research. Pharmacogenetics. 1998;8:283–9.][Relling M., Evans W. Pharmacogenomics in the clinic. Nature. 2015;526:343–50.][Wang C.-W., Preclaro I. A. C., Lin W.-H., Chung W.-H. An Updated Review of Genetic Associations with Severe Adverse Drug Reactions: Translation and Implementation of Pharmacogenomic Testing in Clinical Practice. Front. Pharmacol. 2022;13:886377.][European Medicines Agency. Use of Pharmacogenetic Methodologies in the Pharmacokinetic Evaluation of Medicinal Products — Scientific Guideline. Available at: https://www.ema.europa.eu/en/use-pharmacogenetic-methodologies-pharmacokinetic-evaluation-medicinal-products-scientific-guideline (accessed 01.09.2023).][U.S Food and Drug Administration. Administration Clinical Pharmacogenomics: Premarket Evaluation in Early-Phase Clinical Studies and Recommendations for Labeling. Available at: https://www.fda.gov/regulatory-information/search-fda-guidance-documents/clinical-pharmacogenomics-premarket-evaluation-early-phase-clinical-studies-and-recommendations (accessed 01.09.2023).][U. S. Food and Drug Administration. Table of Pharmacogenetic Associations. Available at: www.fda.gov/medical-devices/precision-medicine/table-pharmacogenetic-associations (accessed 01.09.2023).][Relling M. V., Klein T. E., Gammal R. S., Whirl-Carrillo M., Hoffman J. M., Caudle K. E. The Clinical Pharmacogenetics Implementation Consortium: 10 years later. Clin. Pharmacol. Ther. 2020;107:171–5.][Borobia A. M., Dapia I., Tong H. Y., Arias P., Munoz M., Tenorio J., Hernandez R., Garda Garda I., Gordo G., Ramnez E. Clinical Implementation of Pharmacogenetic Testing in a Hospital of the Spanish National Health System: Strategy and Experience over 3 Years. Clin. Transl. Sci. 2018;11:189–99.][Chen T., O’Donnell P. H., Middlestadt M., Ruhnke G. W., Danahey K., van Wijk X. M., Choksi A., Knoebel R., Hartman S., Yeo K. T. J. Implementation of pharmacogenomics into inpatient general medicine. Pharmacogenetics Genom. 2023;33:19–23.][Magavern E. F., Gurdasani D., Ng F. L., Lee S. S. J. Health equality, race and pharmacogenomics. Br. J. Clin. Pharmacol. 2022;88(1):27–33. doi: 10.1111/bcp. 14983][Popejoy A. B. Diversity in precision medicine and pharmacogenetics: Methodological and conceptual considerations for broadening participation. Pharmgenomics Pers. Med. 2019;12:257–71. doi: 10.2147/PGPM.S179742][Yang H. C., Chen C. W., Lin Y. T., Chu S. K. Genetic ancestry plays a central role in population pharmacogenomics. Commun. Biol. 2021;4:171. doi: 10.1038/s42003- 021-01681-6][Alzubiedi S., Saleh M. I. Pharmacogenetic-guided warfarin dosing algorithm in african-Americans. J. Cardiovasc Pharmacol. 2016;67:86–92. doi: 10.1097/FJC. 0000000000000317][Shendre A., Dillon C., Limdi N. A. Pharmacogenetics of warfarin dosing in patients of African and European ancestry. Pharmacogenomics. 2018;19:1357–71. doi: 10. 2217/pgs-2018-0146][Madla C. M., Gavins F. K. H., Merchant H. A., Orlu M., Murdan S., Basit A. W. Let’s talk about sex: Differences in drug therapy in males and females. Adv. Drug Deliv. Rev. 2021;175:113804. doi: 10.1016/j.addr.2021.05.014][Manteuffel M., Williams S., Chen W., Verbrugge R. R., Pittman D. G., Steinkellner A. Influence of patient sex and gender on medication use, adherence, and prescribing alignment with guidelines. J. Womens Health (Larchmt). 2014;23(2):112–9. doi: 10.1089/jwh.2012.3972][Ravindran T. S., Teerawattananon Y., Tannenbaum C., Vijayasingham L. Making pharmaceutical research and regulation work for women. BMJ. 2020;371:m3808. doi: 10. 1136/bmj.m3808][Mezzalira S., Toffoli G. The effects of sex on pharmacogenetically guided drug treatment. Pharmacogenomics. 2021;22(15):959–62. doi: 10.2217/pgs-2021-0088][Haas D. M., Marsh D. J., Dang D. T., Parker C. B., Wing D. A., Simhan H. N. Prescription and other medication use in pregnancy. Obstet. Gynecol. 2018;131(5):789–98. doi: 10.1097/AOG.0000000000002579][Betcher H. K., George A. L., Jr. Pharmacogenomics in pregnancy. Semin. Perinatol. 2020;44(3):151222. doi: 10.1016/j.semperi.2020.151222][Wall E. H., Hewitt S. C., Case L. K., Lin C. Y., Korach K. S., Teuscher C. The role of genetics in estrogen responses: A critical piece of an intricate puzzle. FASEB J. 2014;28(12):5042–54. doi: 10.1096/fj.14-260307][Moyer A. M., de Andrade M., Faubion S. S., Kapoor E., Dudenkov T., Weinshilboum R. M. SLCO1B1 genetic variation and hormone therapy in menopausal women. Menopause. 2018;25(8):877–82. doi: 10.1097/GME.0000000000001109][Vinogradova Y., Coupland C., Hippisley-Cox J. Use of hormone replacement therapy and risk of venous thromboembolism: Nested case-control studies using the QResearch and CPRD databases. BMJ. 2019;364:k4810. doi: 10.1136/bmj.k4810][Abou-Ismail M. Y., Citla Sridhar D., Nayak L. Estrogen and thrombosis: A bench to bedside review. Thromb. Res. 2020;192:40–51. doi: 10.1016/j.thromres.2020.05.008][Mauvais-Jarvis F., Berthold H. K., Campesi I., Carrero J. J., Dakal S., Franconi F. Sex- and gender-based pharmacological response to drugs. Pharmacol. Rev. 2021;73(2):730–62. doi: 10.1124/pharmrev.120.000206][Huebner T., Steffens M., Scholl C. Current status of the analytical validation of next generation sequencing applications for pharmacogenetic profiling. Mol. Biol. Rep. 2023;50:9587–99.][Koch B. C., van Schaik R. H., van Gelder T., Mathijssen R. H. Rotterdam Clinical Pharmacology Pharmacogenetics Group. Doubt about the feasibility of preemptive genotyping. Clin. Pharmacol. Ther. 2013;93:233.][Wang B., Canestaro W. J., Choudhry N. K. Clinical evidence supporting pharmacogenomic biomarker testing provided in US Food and Drug Administration drug labels. JAMA Intern. Med. 2014;174:1938–44.][Swen J. J., van der Wouden C. H., Manson L. E., Abdullah-Koolmees H., Blagec K., Blagus T., Bohringer S., Cambon-Thomsen A., Cecchin E., Cheung K. C. A 12-gene pharmacogenetic panel to prevent adverse drug reactions: An open-label, multicentre, controlled, cluster-randomised crossover implementation study. Lancet. 2023;401:347–56.][Karamperis K., Koromina M., Papantoniou P., Skokou M., Kanellakis F., Mitropoulos K., Vozikis A., Muller D. J., Patrinos G. P., Mitropoulou C. Economic evaluation in psychiatric pharmacogenomics: A systematic review. Pharmacogenom. J. 2021;21:533–41.][Frueh F. W. Back to the future: Why randomized controlled trials cannot be the answer to pharmacogenomics and personalized medicine. Pharmacogenomics. 2009;10:1077–81.][Visvanathan K., Hurley P., Bantug E., Brown P., Col N. F., Cuzick J., Davidson N. E., DeCensi A., Fabian C., Ford L. Use of pharmacologic interventions for breast cancer risk reduction: American Society of Clinical Oncology clinical practice guideline. J. Clin. Oncol. 2013;31:2942–62.][Relling M. V., Altman R. B., Goetz M. P., Evans W. E. Clinical implementation of pharmacogenomics: Overcoming genetic exceptionalism. Lancet Oncol. 2010;11:507–9.][Morris S. A., Alsaidi A. T., Verbyla A., Cruz A., Macfarlane C., Bauer J., Patel J. N. Cost Effectiveness of Pharmacogenetic Testing for Drugs with Clinical Pharmacogenetics Implementation Consortium (CPIC) Guidelines: A Systematic Review. Clin. Pharmacol. Ther. 2022;112:1318–28.][Kabbani D., Akika R., Wahid A., Daly A. K., Cascorbi I., Zgheib N. K. Pharmacogenomics in practice: A review and implementation guide. Front. Pharmacol. 2023;14:1189976.][Roberts T. A., Wagner J. A., Sandritter T., Black B. T., Gaedigk A., Stancil S. L. Retrospective review of pharmacogenetic testing at an academic children’s hospital. Clin. Transl. Sci. 2021;14(1):412–1. doi: 10.1111/cts.12895][Ramsey L. B., Namerow L. B., Bishop J. R., Hicks J. K., Bousman C., Croarkin P. E. Thoughtful clinical use of pharmacogenetics in child and adolescent psychopharmacology. J. Am. Acad. Child. Adolesc. Psychiatry. 2021;460(6):660–4. doi: 10. 1016/j.jaac.2020.08.006][Hoel R. W., Giddings Connolly R. M., Takahashi P. Y. Polypharmacy management in older patients. Mayo Clin. Proc. 2021;96(1):242–56. doi: 10.1016/j.mayocp. 2020.06.012][Malki M. A., Pearson E. R. Drug-drug-gene interactions and adverse drug reactions. Pharmacogenom. J. 2020;20(3):355–66. doi: 10.1038/s41397-019-0122-0][Inventor B. R., Paun O. Pharmacogenomics in older adults: An integrative review. Res. Gerontol. Nurs. 2021;14(4):211–20. doi: 10.3928/19404921-20210428-01][Karas Kuzelicki N., Prodan Zitnik I., Gurwitz D., Llerena A., Cascorbi I., Siest S., Simmaco M., Ansari M., Pazzagli M., Di Resta C. Pharmacogenomics education in medical and pharmacy schools: Conclusions of a global survey. Pharmacogenomics. 2019;20:643–57.][Leitch T. M., Killam S. R., Brown K. E., Katseanes K. C., George K. M., Schwanke C. Ensuring equity: Pharmacogenetic implementation in rural and tribal communities. Front. Pharmacol. 2022;13:953142. doi: 10.3389/fphar.2022.953142][Naik H., Palaniappan L., Ashley E. A., Scot S. A. Digital health applications for pharmacogenetic clinical trials. Genes. (Basel) 2020;11(11):1261. doi: 10.3390/genes11111261]