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<article article-type="research-article" dtd-version="1.3" xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xml:lang="en"><front><journal-meta><journal-id journal-id-type="publisher-id">rpcardio</journal-id><journal-title-group><journal-title xml:lang="en">Rational Pharmacotherapy in Cardiology</journal-title><trans-title-group xml:lang="ru"><trans-title>Рациональная Фармакотерапия в Кардиологии</trans-title></trans-title-group></journal-title-group><issn pub-type="ppub">1819-6446</issn><issn pub-type="epub">2225-3653</issn><publisher><publisher-name>«SILICEA-POLIGRAF» LLC</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="doi">10.20996/1819-6446-2021-02-04</article-id><article-id custom-type="elpub" pub-id-type="custom">rpcardio-2396</article-id><article-categories><subj-group subj-group-type="heading"><subject>Research Article</subject></subj-group><subj-group subj-group-type="section-heading" xml:lang="en"><subject>POINT OF VIEW</subject></subj-group><subj-group subj-group-type="section-heading" xml:lang="ru"><subject>ТОЧКА ЗРЕНИЯ</subject></subj-group></article-categories><title-group><article-title>Pharmacogenetics as a Way for Personalizing Diuretic Therapy: Focus on Torasemide</article-title><trans-title-group xml:lang="ru"><trans-title>Фармакогенетика как инструмент персонализации диуретической терапии: фокус на торасемид</trans-title></trans-title-group></title-group><contrib-group><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0001-5897-3532</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Гафурова</surname><given-names>Н. М.</given-names></name><name name-style="western" xml:lang="en"><surname>Gafurova</surname><given-names>N. M.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Гафурова Нупайсат Магомедовна </p><p>Москва</p><p>eLibrary SPIN 9049-3287</p></bio><bio xml:lang="en"><p>Nupaysat M. Gafurova</p><p>Moscow</p><p>eLibrary SPIN 9049-3287</p></bio><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0001-6589-7654</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Ших</surname><given-names>Е. В.</given-names></name><name name-style="western" xml:lang="en"><surname>Shikh</surname><given-names>E. V.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Ших Евгения Валерьевна </p><p>Москва</p><p>eLibrary SPIN 2397-8414</p></bio><bio xml:lang="en"><p>Evgenia V. Shikh</p><p>Moscow</p><p>eLibrary SPIN 2397-8414</p></bio><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-0795-8225</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Остроумова</surname><given-names>О. Д.</given-names></name><name name-style="western" xml:lang="en"><surname>Ostroumova</surname><given-names>O. D.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Остроумова Ольга Дмитриевна </p><p>Москва</p><p>eLibrary SPIN 3910-6585</p></bio><bio xml:lang="en"><p>Olga D. Ostroumova</p><p>Moscow</p><p>eLibrary SPIN 3910-6585</p></bio><email xlink:type="simple">nupa@mail.ru</email><xref ref-type="aff" rid="aff-2"/></contrib></contrib-group><aff-alternatives id="aff-1"><aff xml:lang="ru"><institution>Первый Московский государственный медицинский университет им. И.М. Сеченова (Сеченовский Университет)</institution><country>Россия</country></aff><aff xml:lang="en"><institution>I.M. Sechenov First Moscow State Medical University (Sechenov University)</institution><country>Russian Federation</country></aff></aff-alternatives><aff-alternatives id="aff-2"><aff xml:lang="ru"><institution>Первый Московский государственный медицинский университет им. И.М. Сеченова (Сеченовский Университет);&#13;
Российская медицинская академия непрерывного профессионального образования</institution><country>Россия</country></aff><aff xml:lang="en"><institution>I.M. Sechenov First Moscow State Medical University (Sechenov University);&#13;
Russian Medical Academy of Continuous Professional Education</institution><country>Russian Federation</country></aff></aff-alternatives><pub-date pub-type="collection"><year>2021</year></pub-date><pub-date pub-type="epub"><day>02</day><month>03</month><year>2021</year></pub-date><volume>17</volume><issue>1</issue><fpage>119</fpage><lpage>123</lpage><permissions><copyright-statement>Copyright &amp;#x00A9; Gafurova N.M., Shikh E.V., Ostroumova O.D., 2021</copyright-statement><copyright-year>2021</copyright-year><copyright-holder xml:lang="ru">Гафурова Н.М., Ших Е.В., Остроумова О.Д.</copyright-holder><copyright-holder xml:lang="en">Gafurova N.M., Shikh E.V., Ostroumova O.D.</copyright-holder><license xml:lang="ru" license-type="creative-commons-attribution" xlink:href="https://creativecommons.org/licenses/by/4.0/" xlink:type="simple"><license-p>Данная работа распространяется под лицензией Creative Commons Attribution 4.0.</license-p></license><license xml:lang="en" license-type="creative-commons-attribution" xlink:href="https://creativecommons.org/licenses/by/4.0/" xlink:type="simple"><license-p>This work is licensed under a Creative Commons Attribution 4.0 License.</license-p></license></permissions><self-uri xlink:href="https://www.rpcardio.online/jour/article/view/2396">https://www.rpcardio.online/jour/article/view/2396</self-uri><abstract><p>Optimizing diuretic therapy in patients with chronic heart failure is a complicated problem with many unresolved questions. Diuretics take an important place in the treatment of heart failure, which are used in almost 80% of cases. Currently, there are not enough clinical studies, which comparative effectiveness of loop diuretics, as well as studies aimed at personalizing diuretic therapy. Torasemide has several advantages over other loop diuretics; high bioavailability, longer half-life and duration of action provide predictable diuresis. The presence of favorable neurohormonal effects, consisting in a decrease of sympathetic activity and inhibition of the renin-angiotensin-aldosterone system, leads to the fact that hypokalemia rarely occurs. In addition, torasemide slows development of myocardial fibrosis and fosters reverse ventricular remodelling. The use of personalization methods is one of the ways to increase the efficiency and safety of pharmacotherapy with diuretics. The polymorphism of genes encoding systems of biotransformation and transporters of drug is an important factor that determines the individual characteristics of a patient. Pharmacogenetics of torasemide may be of significant importance for pharmacokinetics and pharmacodynamics, influencing the intensity of the diuretic effect and side effects. The clearance of torasemide after oral administration may vary by 47% due to genetic characteristics: the participation of the OATP1B1 polymorphism is approximately 15.5%, the CYP2C9 polymorphism is 20%, and the OAT1 and OAT4 polymorphisms are 10%. Due to the significant differences in the pharmacokinetics of torasemide, further study of the pharmacodynamic characteristics of torasemide in patients with genetic polymorphism is necessary.</p></abstract><trans-abstract xml:lang="ru"><p>Оптимизация диуретической терапии у пациентов с хронической сердечной недостаточностью является сложной задачей со многими нерешенными вопросами. В терапии сердечной недостаточности важное место занимают диуретики, которые применяются почти в 80% случаев. В настоящее время недостаточно клинических исследований по изучению сравнительной эффективности петлевых диуретиков, а также исследований, направленных на персонализацию диуретической терапии. Торасемид имеет ряд преимуществ по сравнению с другими петлевыми диуретиками: высокая биодоступность, более длительный период полувыведения и продолжительность действия обеспечивают предсказуемый диурез. Наличие благоприятных нейрогормональных эффектов, заключающихся в снижении симпатической активности и ингибировании ренин-ангиотензин-альдостероновой системы, приводит к тому, что торасемид редко вызывает гипокалиемию. Кроме того, торасемид замедляет фиброз миокарда и способствует обратному ремоделированию желудочков. Одним из путей повышения эффективности и безопасности фармакотерапии диуретиками является применение методов персонализации. Полиморфизм генов, кодирующих системы биотрансформации и транспортеров лекарственных средств, является важным фактором, определяющим индивидуальные особенности пациента. Фармакогенетика торасемида может иметь существенное значение для фармакокинетики и фармакодинамики, оказывая влияние на выраженность диуретического эффекта и побочных явлений. Клиренс торасемида при пероральном приеме варьирует на 46,7% вследствие генетических особенностей: доля участия полиморфизма OATP1B1 составляет 15,5%, полиморфизма CYP2C9 – примерно 20%, полиморфизма ОАТ1 и ОАТ4 – около 10%. Значимые различия в фармакокинетике торасемида указывают на необходимость дальнейшего изучения особенностей фармакодинамики и переносимости торасемида у пациентов с генетическими полиморфизмами.</p></trans-abstract><kwd-group xml:lang="ru"><kwd>петлевые диуретики</kwd><kwd>торасемид</kwd><kwd>полиморфизм CYP2C9</kwd><kwd>белки-транспортеры</kwd><kwd>фармакокинетика</kwd></kwd-group><kwd-group xml:lang="en"><kwd>loop diuretics</kwd><kwd>torasemide</kwd><kwd>CYP2C9 polymorphism</kwd><kwd>membrane transport proteins</kwd><kwd>pharmacokinetics</kwd></kwd-group></article-meta></front><back><ref-list><title>References</title><ref id="cit1"><label>1</label><citation-alternatives><mixed-citation xml:lang="ru">Braunwald E. The war against heart failure: the Lancet lecture. Lancet. 2015;385(9970):812-24. DOI:10.1016/S0140-6736(14)61889-4.</mixed-citation><mixed-citation xml:lang="en">Braunwald E. The war against heart failure: the Lancet lecture. Lancet. 2015;385(9970):812-24. 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