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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="ru"><front><journal-meta><journal-id journal-id-type="publisher-id">ssmu</journal-id><journal-title-group><journal-title xml:lang="ru">Бюллетень сибирской медицины</journal-title><trans-title-group xml:lang="en"><trans-title>Bulletin of Siberian Medicine</trans-title></trans-title-group></journal-title-group><issn pub-type="ppub">1682-0363</issn><issn pub-type="epub">1819-3684</issn><publisher><publisher-name>Siberian State Medical University, the Ministry of Healthcare of the Russian Federation</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="doi">10.20538/1682-0363-2019-4-119-126</article-id><article-id custom-type="elpub" pub-id-type="custom">ssmu-2564</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="ru"><subject>ОРИГИНАЛЬНЫЕ СТАТЬИ</subject></subj-group><subj-group subj-group-type="section-heading" xml:lang="en"><subject>ORIGINAL PAPERS</subject></subj-group></article-categories><title-group><article-title>Взаимосвязь полиморфизма CYP2C19*17 с показателями эффективности и безопасности диазепама у пациентов с синдромом отмены алкоголя</article-title><trans-title-group xml:lang="en"><trans-title>The relationship between the CYP2C19*17 genetic polymorphism and the efficacy and safety of diazepam in patients with alcohol withdrawal syndrome</trans-title></trans-title-group></title-group><contrib-group><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-4942-8556</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Скрябин</surname><given-names>В. Ю.</given-names></name><name name-style="western" xml:lang="en"><surname>Skryabin</surname><given-names>V. Yu.</given-names></name></name-alternatives><bio xml:lang="ru"><p>зав. 16-м наркологическим отделением,</p><p>109390, г. Москва, ул. Люблинская, 37/</p></bio><bio xml:lang="en"><p>Head of the Department No. 16,</p><p>37/1, Lyublinskaya Str., Moscow, 109390</p></bio><email xlink:type="simple">sardonios@yandex.ru</email><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-3964-9726</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Застрожин</surname><given-names>М. С.</given-names></name><name name-style="western" xml:lang="en"><surname>Zastrozhin</surname><given-names>M. S.</given-names></name></name-alternatives><bio xml:lang="ru"><p>канд. мед. наук, руководитель лаборатории генетики и фундаментальных исследований, 109390, г. Москва, ул. Люблинская, 37/1;</p><p>ассистент, кафедра наркологии, 125993, г. Москва, ул. Баррикадная, 2/1, стр. 1</p></bio><bio xml:lang="en"><p>PhD, Head of the Laboratory of Genetics and Fundamental, 37/1, Lyublinskaya Str., Moscow, 109390;</p><p>Assistant, Addiction Psychiatry Department, 2/1 Barrikadnaya Str., Moscow, 123995</p></bio><xref ref-type="aff" rid="aff-2"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-5621-8266</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Гришина</surname><given-names>Е. А.</given-names></name><name name-style="western" xml:lang="en"><surname>Grishina</surname><given-names>E. A.</given-names></name></name-alternatives><bio xml:lang="ru"><p>канд. биол. наук, зав. отделом молекулярно-биологических исследований,</p><p>125993, г. Москва, ул. Баррикадная, 2/1, стр. 1</p></bio><bio xml:lang="en"><p>PhD, Head of the Biomolecular Researchers Department,</p><p>2/1 Barrikadnaya Str., Moscow, 123995</p></bio><xref ref-type="aff" rid="aff-3"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0003-3505-8520</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Рыжикова</surname><given-names>К. А.</given-names></name><name name-style="western" xml:lang="en"><surname>Ryzhikova</surname><given-names>K. A.</given-names></name></name-alternatives><bio xml:lang="ru"><p>науч. сотрудник, отдел молекулярно-биологических исследований,</p><p>125993, г. Москва, ул. Баррикадная, 2/1, стр. 1</p></bio><bio xml:lang="en"><p>Researcher, Biomolecular Researchers Department Russian,</p><p>2/1 Barrikadnaya Str., Moscow, 123995</p></bio><xref ref-type="aff" rid="aff-3"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0003-1100-7817</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Шипицын</surname><given-names>В. В.</given-names></name><name name-style="western" xml:lang="en"><surname>Shipitsyn</surname><given-names>V. V.</given-names></name></name-alternatives><bio xml:lang="ru"><p>зам. директора по медицинской части,</p><p>109390, г. Москва, ул. Люблинская, 37/1</p></bio><bio xml:lang="en"><p>Deputy Director,</p><p>37/1, Lyublinskaya Str., Moscow, 109390</p></bio><xref ref-type="aff" rid="aff-4"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-6097-737X</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Барна</surname><given-names>И. В.</given-names></name><name name-style="western" xml:lang="en"><surname>Barna</surname><given-names>I. V.</given-names></name></name-alternatives><bio xml:lang="ru"><p>врач психиатр-нарколог, 16-е наркологическое отделение, </p><p>109390, г. Москва, ул. Люблинская, 37/1</p></bio><bio xml:lang="en"><p>Addiction Psychiatrist, Department No.16,</p><p>37/1, Lyublinskaya Str., Moscow, 109390</p></bio><xref ref-type="aff" rid="aff-4"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0003-1950-1043</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Галактионова</surname><given-names>Т. Е.</given-names></name><name name-style="western" xml:lang="en"><surname>Galaktionova</surname><given-names>T. E.</given-names></name></name-alternatives><bio xml:lang="ru"><p>врач психиатр-нарколог, 16-е наркологическое отделение,</p><p>109390, г. Москва, ул. Люблинская, 37/1</p></bio><bio xml:lang="en"><p>Addiction Psychiatrist, Department No.16, </p><p>37/1, Lyublinskaya Str., Moscow, 109390</p></bio><xref ref-type="aff" rid="aff-4"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-5450-244X</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Сорокин</surname><given-names>А. С.</given-names></name><name name-style="western" xml:lang="en"><surname>Sorokin</surname><given-names>A. S.</given-names></name></name-alternatives><bio xml:lang="ru"><p>лаборант-исследователь, молекулярно-генетическая лаборатория, </p><p>109390, г. Москва, ул. Люблинская, 37/1</p></bio><bio xml:lang="en"><p>Research Assistant, Laboratory of Genetics and Fundamental,</p><p>37/1, Lyublinskaya Str., Moscow, 109390</p></bio><xref ref-type="aff" rid="aff-4"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-8366-9732</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Брюн</surname><given-names>Е. А.</given-names></name><name name-style="western" xml:lang="en"><surname>Bryun</surname><given-names>E. A.</given-names></name></name-alternatives><bio xml:lang="ru"><p>президент, 109390, г. Москва, ул. Люблинская, 37/1;</p><p>д-р мед. наук, профессор, зав. кафедрой наркологии, 125993, г. Москва, ул. Баррикадная, 2/1, стр. 1</p></bio><bio xml:lang="en"><p>DM, Professor, President of the Moscow Department of Healthcare,</p><p>37/1, Lyublinskaya Str., Moscow, 109390;</p><p>2/1 Barrikadnaya Str., Moscow, 123995</p></bio><xref ref-type="aff" rid="aff-2"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-4496-3680</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Сычёв</surname><given-names>Д. А.</given-names></name><name name-style="western" xml:lang="en"><surname>Sychev</surname><given-names>D. A.</given-names></name></name-alternatives><bio xml:lang="ru"><p>д-р мед. наук, профессор, член-корр. РАН, зав. кафедрой клинической фармакологии и терапии, </p><p>125993, г. Москва, ул. Баррикадная, 2/1, стр. 1</p></bio><bio xml:lang="en"><p>DM, Professor, Corresponding Member of the Academy of Sciences of Russia, Head of Clinical Pharmacology and Therapy Department, </p><p>2/1 Barrikadnaya Str., Moscow, 123995</p></bio><xref ref-type="aff" rid="aff-3"/></contrib></contrib-group><aff-alternatives id="aff-1"><aff xml:lang="ru"><institution>Московский научно-практический центр (МНПЦ) наркологии Департамента здравоохранения Москвы (ДЗМ)1</institution><country>Россия</country></aff><aff xml:lang="en"><institution>Moscow Research and Practical Centre on Addictions of the Moscow Department of Healthcare</institution><country>Russian Federation</country></aff></aff-alternatives><aff-alternatives id="aff-2"><aff xml:lang="ru"><institution>Московский научно-практический центр (МНПЦ) наркологии Департамента здравоохранения Москвы (ДЗМ);&#13;
Российская медицинская академия непрерывного профессионального образования (РМАНПО)</institution><country>Россия</country></aff><aff xml:lang="en"><institution>Moscow Research and Practical Centre on Addictions of the Moscow Department of Healthcare;&#13;
Russian Medical Academy of Continuous Professional Education of the Ministry of Health of the Russian Federation</institution><country>Russian Federation</country></aff></aff-alternatives><aff-alternatives id="aff-3"><aff xml:lang="ru"><institution>Российская медицинская академия непрерывного профессионального образования (РМАНПО)</institution><country>Россия</country></aff><aff xml:lang="en"><institution>Russian Medical Academy of Continuous Professional Education of the Ministry of Health of the Russian Federation</institution><country>Russian Federation</country></aff></aff-alternatives><aff-alternatives id="aff-4"><aff xml:lang="ru"><institution>Московский научно-практический центр (МНПЦ) наркологии Департамента здравоохранения Москвы (ДЗМ)</institution><country>Россия</country></aff><aff xml:lang="en"><institution>Moscow Research and Practical Centre on Addictions of the Moscow Department of Healthcare</institution><country>Russian Federation</country></aff></aff-alternatives><pub-date pub-type="collection"><year>2019</year></pub-date><pub-date pub-type="epub"><day>14</day><month>01</month><year>2020</year></pub-date><volume>18</volume><issue>4</issue><fpage>119</fpage><lpage>126</lpage><permissions><copyright-statement>Copyright &amp;#x00A9; Скрябин В.Ю., Застрожин М.С., Гришина Е.А., Рыжикова К.А., Шипицын В.В., Барна И.В., Галактионова Т.Е., Сорокин А.С., Брюн Е.А., Сычёв Д.А., 2020</copyright-statement><copyright-year>2020</copyright-year><copyright-holder xml:lang="ru">Скрябин В.Ю., Застрожин М.С., Гришина Е.А., Рыжикова К.А., Шипицын В.В., Барна И.В., Галактионова Т.Е., Сорокин А.С., Брюн Е.А., Сычёв Д.А.</copyright-holder><copyright-holder xml:lang="en">Skryabin V.Y., Zastrozhin M.S., Grishina E.A., Ryzhikova K.A., Shipitsyn V.V., Barna I.V., Galaktionova T.E., Sorokin A.S., Bryun E.A., Sychev D.A.</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://bulletin.ssmu.ru/jour/article/view/2564">https://bulletin.ssmu.ru/jour/article/view/2564</self-uri><abstract><p>Цель исследования – изучение взаимосвязи полиморфизма гена CYP2C19 с показателямиэффективности и безопасности диазепама у пациентов с синдромом отмены алкоголя дляснижения риска развития дозозависимых нежелательных лекарственных реакций (НЛР) ифармакорезистентности.</p><sec><title>Материалы и методы</title><p>Материалы и методы. Исследование проведено на 30 русских пациентах мужского пола (среднийвозраст – (44,6 ± 10,4) года) с установленным диагнозом синдрома отмены алкоголя. Пациентыс целью терапии аффекта тревоги, страха и эмоциональной напряженности в рамках синдромаотмены алкоголя получали в течение 5 сут диазепам в форме раствора для внутримышечных и внутривенных инъекций в дозировке 30 мг/сут. Генотипирование производилось методом полимеразной цепной реакции в режиме реального времени с аллель-специфической гибридизацией. Оценкаэффективности и безопасности осуществлялась с помощью психометрических шкал и шкал оценкивыраженности НЛР: международной шкалы оценки тяжести синдрома отмены алкоголя CIWA-Ar,визуально-аналоговой шкалы оценки влечения к алкоголю, шкалы оценки побочного действия.</p></sec><sec><title>Результаты</title><p>Результаты. Установлены различия в показателе эффективности терапии у пациентов с разнымигенотипами по полиморфному маркеру -806C&gt;T гена CYP2C19: (CC) –12,0 [–15,0; –8,0], (CT + TT)–7,0 [–14,0; –5,0], p = 0,001. Баллы по шкале UKU, с помощью которой оценивалась безопасность,также различались: (CC) 8,0 [6,0; 12,0], (CT + TT) 6,0 [6,0; 12,0], p = 0,006.</p></sec><sec><title>Заключение</title><p>Заключение. Показано, что полиморфизм гена CYP2C19 может быть связан с показателямиэффективности и безопасности терапии диазепамом у пациентов с синдромом отмены алкоголя. Этонеобходимо учитывать при назначении данного лекарственного средства таким пациентам с цельюснижения риска развития нежелательных реакций и фармакорезистентности.</p></sec></abstract><trans-abstract xml:lang="en"><p>The aim of our study was to study the relationship between the CYP2C19 genetic polymorphism and the efficacy and safety of diazepam in patients with alcohol withdrawal syndrome in order to develop algorithms for optimizing the therapy of diazepam to reduce the risk of dose-dependent adverse drug reactions and pharmacoresistance.</p><sec><title>Materials and methods</title><p>Materials and methods. The study was conducted on 30 Russian male patients suffering from alcohol withdrawal syndrome. For the treatment of anxiety, fear and emotional tension, patients received diazepam in injections at a dosage of 30,0 mg / day for 5 days. Genotyping was performed by real-time polymerase chain reaction with allele-specific hybridization. The efficacy and safety assessment was performed using psychometric scales and scales for assessing the severity of adverse drug reactions: the Clinical Institute Withdrawal Assessment for Alcohol scale, the visual-analogue scale of the craving for alcohol, and the side-effect scale.</p></sec><sec><title>Results</title><p>Results. Based on the results of the study, we revealed the differences in the efficacy of therapy in patients with different CYP2C19 -806C&gt;T genotypes: (CC) –12,0 [–15,0; –8,0], (CT + TT) –7.0 [–14,0; –5,0], p = 0,001. The scores on the UKU scale, which was used to evaluate the safety of therapy, were also different: (CC) 8,0 [6,0; 12,0], (CT + TT) 6,0 [6,0; 12,0], p = 0,006.</p></sec><sec><title>Conclusion</title><p>Conclusion. The relationships between the CYP2C19 genetic polymorphism and the efficacy and safety of diazepam were demonstrated. This should be taken into consideration when prescribing this drug to such patients in order to reduce the risk of adverse drug reactions and pharmacoresistance. </p></sec></trans-abstract><kwd-group xml:lang="ru"><kwd>фармакогенетика</kwd><kwd>бензодиазепины</kwd><kwd>диазепам</kwd><kwd>биотрансформация</kwd><kwd>персонализированная медицина</kwd><kwd>CYP2C19</kwd><kwd>синдром отмены алкоголя</kwd></kwd-group><kwd-group xml:lang="en"><kwd>pharmacogenetics</kwd><kwd>benzodiazepines</kwd><kwd>diazepam</kwd><kwd>biotransformation</kwd><kwd>personalized medicine</kwd><kwd>CYP2C19</kwd><kwd>alcohol withdrawal syndrome</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">Fukasawa T., Suzuki A., Otani K. Effects of genetic polymorphism of cytochrome P450 enzymes on the pharmacokinetics of benzodiazepines. J. Clin. Pharm. 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