Фармакогенетика – молекулярные основы эффективной и безопасной лекарственной терапии

Сфармакогенетических феноменах, определяющих индивидуальные реакции на лекарственные средства в зависимости от наследственно детерминированных особенностей биотрансформации, взаимодействия с рецепторными образованиями, ферментными системами, практических возможностях прогноза индивидуальных эффектов. Механизмы взаимодействия лекарства с организмом человека, генетически обусловленные индивидуальные различия в эффектах лекарственных средств следует рассматривать как очередную закономерность, поскольку все фармакодинамические процессы, фармакокинетика и метаболизм лекарств опосредованы белковыми образованиями, рецепторами, сопряженными с ними ионными каналами, переносчиками, ферментами синтеза и метаболизма эндогенных лигандов рецепторов, различного рода модуляторами, включая пептидные, ферментами, метаболизирующими лекарства. Эти механизмы ДНК-зависимые, что определяет их индивидуальность, таким образом, ответ на действие лекарственного средства определяет совокупность генетических и внешних средовых факторов, но при этом приобретенные свойства модифицируют генетически зависимые механизмы. Выяснение роли генетических и средовых факторов для каждого пациента требуется проводить индивидуально. Важно знать наследственные механизмы формирования индивидуальных реакций на лекарственные средства.

1. Kostjuk S.A. Modern achievements and basic principles of epigenetics: simple about the complex. Medicinskie novosti, 2020, no. 9, pp. 4-8. (in Russian).

2. Kostjuk S.A. Genes of predisposition to multifactorial diseases and genetic polymorphism: what is it? Medicinskie novosti, 2020, no. 7, pp. 45-49. (in Russian).

3. Kostjuk S.A. Molecular biological methods in medicine: monograph. Minsk: BelMAPO, 2013, 327 p. (in Russian).

4. Kostjuk S.A. Predictive medicine and genetic testing methods. Medicinskie novosti, 2016, no. 4, pp. 11-14. (in Russian).

5. Kostjuk S.A. Modern directions of using molecular genetic analysis in diagnostics of rheumatic diseases. Medicinskie novosti. 2017, no. 11, pp. 18-23. (in Russian).

6. Kostjuk S.A. Diagnostic and prognostic value of molecular biological markers of oncogenesis and the effectiveness of antitumor therapy. Medicinskie novosti, 2016, no. 7, pp. 2-7. (in Russian).

7. Kostjuk S.A., Davidovskij S.V., Kostjuk D.D. et al. Genetic determination of human psychological characteristics. Medicinskie novosti. 2021, no. 6, pp. 28-32. (in Russian).

8. Kostjuk S.A., Davidovskij S.V., Kostjuk D.D. et al. Genetic control of susceptibility to suicide and aggressive behavior. Problemy zdorovja i jekologii, 2021, vol. 18, no. 3, pp. 23-32. (in Russian).

9. Sychev D.A., Kantemirova B.I. Modern biomarkers as tools for patient-oriented medicine: pharmacogenetics and beyond. Farmakogenetika i farmakogenomika, 2022, no. 1, pp. 3-5. (in Russian).

10. Sacristán J.A. Patient-centered medicine and patient-oriented research: improving health outcomes for individual patients. BMC Med Inform Decis Mak, 2013, no. 13, pp. 6. doi: 10.1186/1472-6947-13-6.

11. Sychev D.A. “Multiomic” Studies as a Promising Clinical Pharmacological Tool for Personalization of Socially Significant Diseases Pharmacotherapy in Russia. Personalized Psychiatry and Neurology, 2022, vol. 2, no. 2, pp. 1-2.

12. Ashihmin Ja.I. Translational Medicine: New Hope or a Cunning Plan of the Pharmaceutical Industry? Farmakogenetika i farmakogenomika, 2015, no. 1, pp. 40-44. (in Russian).

13. Kukesa V.G., Bochkova N.P eds. Clinical pharmacogenetics. M.: GJeOTAR-Media, 2007, 248 p. (in Russian).

14. Seredenin S.B. Lectures on pharmacogenetics. M.: MIA, 2004, 303 p. (in Russian).

15. Leonova M.V. Strategy and technologies for dissemination and implementation of pharmacogenomics in clinical practice: foreign experience. Farmakogenetika i farmakogenomika, 2024, no. 1, pp. 44-52. (in Russian).

16. Licinio L., Wong M.L. eds. Pharmacogenomics. The Search for Individualized Therapies. Weinheim (Germany): WILEY-VCH Verlag GmbH, 2002. 585 p.

17. Kukes V.G. Clinical pharmacology. M.: GJeOTAR-Media, 2008, 304 p. (in Russian).

18. Kalow W. Pharmacogenetics: Heredity and Response to Drugs. Philadelphia: W.B. Saunders, PA, 1962.

19. Miroshnikova V.V., Pchelina S.N., Donnikov M.Ju. et al. Genetic testing in cardiology using NGS panel: from disease risk assessment to pharmaco - ge netics. Farmakogenetika i farmakogenomika, 2023, no. 1, pp. 7-19. (in Russian).

20. Kostjuk S.A., Polujan O.S., Rudenkova T.V. Using real-time PCR to substantiate personalized laboratory diagnostic tactics and treatment regimens for multifactorial diseases based on identifying features of changes in the genomes of diploid organisms. Laboratornaja diagnostika. Vostochnaja Evropa, 2021, vol. 10, no. 2, pp. 146-158. (in Russian).

21. Davidouski S.V., Ibragimova Zh.A., Babenka A.S. et al. Experience of using the molecular genetic studies to assess the risk of suicide. Proceedings of the National Academy of Sciences of Belarus, Medical series. 2021, vol. 18, no. 4, pp. 483-490.

22. Kindmark A., Jawaid A., Harbron C.G. et al. Genome-wide pharmacogenetic investigation of a hepatic adverse event without clinical signs of immunopathology suggests an underlying immune pathogenesis. Pharmacogenomics J, 2008, vol. 8., no. 3, pp. 186-195.

23. Swen J.J., Huizinga T.W., Gelderblom H. et al. Translating Pharmacogenomics: Challenges on the Road to the Clinic. PLoS Med. 2007, vol. 4., no. 8, pp. e209.

24. Koh N.V., Cvetovskaja G.A., Novikova Ja.V. et al. Contribution of genetic markers to changes in the therapeutic dosage of warfarin]. Vestnik NGU. Serija: Biologija, klinicheskaja medicina, 2011, vol. 9, no. 4, pp. 148-155. (in Russian).

25. Wadelius M., Chen L.Y., Eriksson N. et al. Association of warfarin dose with genes involved in its action and metabolism. Human Genetics, 2007, vol. 121, no. 1, pp. 23-24.

26. Guidelines. Bioequivalence assessment of medicinal products. Moskva, 2008, 32 p. (in Russian).

27. Recommendations for pharmaceutical companies on studying biotransformation and transporters of new drugs: study design, data analysis and inclusion of information in instructions for use. М., 2009.

28. Matsui S. Genomic Biomarkers for Personalized Medicine: Development and Validation in Clinical Studies. Computational and Mathematical Methods in Medicine, 2013, vol. 2013, pp. 865980.

29. Reflection Paper on Pharmacogenomic Samples, Testing and Data Handling. London, 2007. 8 p.

30. Reflection Paper on the use of Pharmacogenetics in the Pharmacokinetic Evaluation of Medicinal Products. London: 2006. 7 p.

31. Guidance for Industry Clinical. Pharmacogenomics: Premarket Evaluation in Early-Phase Clinical Studies and Recommendations for Labeling. USA: Food and Drug Administration, 2013. 26 p.

32. Rudenkova T.V., Kostjuk S.A., Klimkovich N.N., Demidenko A.N. Polymorphism of cytochrome P450 genes in patients with acute lymphoblastic and acute myeloblastic leukemia. Laboratornaja diagnostika. Vostochnaja Evropa, 2023, vol. 12, no. 3, pp. 347-357. (in Russian).

33. US Food and Drug Administration. Table of Pharmacogenomic Biomarkers in Drug Labels. Available at: https://www.fda.gov/drugs/science-and-research-drugs/table-pharmacogenomic-biomarkers-drug-labeling (accessed 21.05.2025).

34. Weber W.W. Pharmacogenetics. Oxford: Oxford University Press, 1997. 344 p.

35. Kalow W., Meyer U.A., Tyndale R. eds. Pharmacogenomics. New York: Marcel Dekker, 2001. 403 p.