medsovetМедицинский СоветMeditsinskiy sovet = Medical Council2079-701X2658-5790REMEDIUM GROUP Ltd.10.21518/2079-701X-2018-21-204-209medsovet-2838Research ArticleПрактикаPracticeФармакогенетика нестероидных противовоспалительных препаратов: существующие проблемы для клинической практикиPharmacogenetics of non-steroidal anti-inflammatory drugs: existing problems for clinical practiceЛеоноваМ. В.LeonovaM. V.

Леонова Марина Васильевна – доктормедицинских наук, профессор, член-корреспондент РАЕН, клинический фармаколог, член Межрегиональной общественной организации Ассоциация клинических фармакологов России

117997, г. Москва,ул. Островитянова, д. 1

Leonova Marina Vasilievna – Dr. of Sci. (Med.), Professor, Corr.Member of RANS, Clinical Pharmacologist, Member of the Interregional Public Organization: Association of Clinical Pharmacologists of Russia

1 Ostrovityanova, Moscow, 117997 

anti23@mail.ruАлимоваЭ. Э.AlimovaE. E.

Алимова Эльмира Эрфановна – кандидат медицинских наук, доцент кафедры клинической фармакологии лечебного факультета

117997, г. Москва,ул. Островитянова, д. 1

Alimova Elmira Erfanovna – Cand. of Sci. (Med.), Associate Professor of the Department of Clinical Pharmacology, Faculty of General Medicine

1 Ostrovityanova, Moscow, 117997 

alimovaee@yandex.ruФедеральное государственное бюджетное образовательное учреждение высшего образования «Российский национальный исследовательский медицинский университет имени Н.И. Пирогова» Министерства здравоохранения Российской ФедерацииРоссияFederal State Budgetary Educational Institution of Higher Education “Pirogov Russian National Research Medical University” of the Ministry of Health of RussiaRussian Federation201820012019021204209Copyright © Леонова М.В., Алимова Э.Э., 20192019Леонова М.В., Алимова Э.Э.Leonova M.V., Alimova E.E.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.med-sovet.pro/jour/article/view/2838

НПВП относятся к наиболее часто применяемым лекарственным средствам в клинической практике для обезболивания при различных заболеваниях. К настоящему времени накоплен значительный научный материал по фармакогенетике НПВП и роли генетических факторов, которые могут влиять на фармакокинетику и фармакодинамику препаратов, изменяя эффективность и профиль токсичности. Наиболее клинически значимые изменения в фармакокинетике у носителей медленных аллелей CYP2С9*3 выявлены для целекоксиба и флурбипрофена, что определяет необходимость тестирования и снижения доз препаратов. Проведены исследования по изучению роли полиморфизма метаболизирующих ферментов CYP2C9, CYP2C8, UGT в развитии гастротоксичности и желудочно-кишечных кровотечений на фоне приема НПВП, а также гепатотоксичности диклофенака. Показана ассоциация «медленных» аллелей CYP2C8*3 и CYP2C9*2,*3 с риском развития желудочно-кишечных кровотечений, связанных с приемом НПВП, которые являются субстратами CYP2C9 и CYP2C8. Изучено воздействие вариантов аллелей PTGS1 (гена ЦОГ-1) и PTGS2 (гена ЦОГ-2) на фармакодинамику, эффективность и токсичность НПВП, в частности на выраженность аналгезирующего эффекта и кардиотоксичность препаратов. Таким образом, определены фармакогенетические предикторы неблагоприятных эффектов, которые пациенты могут испытывать, и необходимость коррекции дозы на основе генотипа пациента или индивидуализации выбора альтернативных НПВП для повышения эффективности обезболивания.

NSAIDs are the most commonly used drugs in clinical practice for pain relief in various diseases. To date, considerable scientific material has been accumulated on the pharmacogenetics of NSAIDs and the role of genetic factors that can influence the pharmacokinetics and pharmacodynamics of drugs, changing the efficacy and toxicity profile. The most clinically significant changes in pharmacokinetics in carriers of slow alleles of CYP2C9*3 have been identified for celecoxib and flurbiprofen, which determines the need for testing and lowering of drug doses. Studies were carried out to study the role of polymorphism of the metabolizing enzymes CYP2C9, CYP2C8, UGT in the development of gastrotoxicity and gastrointestinal bleeding during application NSAIDs, as well as diclofenac’s hepatotoxicity. The association of «slow» alleles CYP2C8*3 and CYP2C9*2,*3 with the risk of gastrointestinal bleeding associated with NSAID use, which are substrates of CYP2C9 and CYP2C8, is shown. The effect of variants of alleles PTGS1 (gene COX-1) and PTGS2 (gene COX-2) on pharmacodynamics, efficacy and toxicity of NSAIDs, in particular, the severity of the analgesic effect and cardiotoxicity of the drugs, was studied. In this way, pharmacogenetic predictors of adverse effects that patients can experience, and the need for dose adjustment based on the patient’s genotype, or individualizing the choice of alternative NSAIDs to increase the effectiveness of analgesia, have been determined.

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The authors declare that there are no conflicts of interest present.