Annals of the Russian academy of medical sciencesAnnals of the Russian academy of medical sciencesВестник Российской академии медицинских наук0869-60472414-3545"Paediatrician" Publishers LLC121410.15690/vramn1214CARDIOLOGY AND CARDIOVASCULAR SURGERY: CURRENT ISSUESАКТУАЛЬНЫЕ ВОПРОСЫ КАРДИОЛОГИИ И СЕРДЕЧНО-СОСУДИСТОЙ ХИРУРГИИReview ArticleClinical pharmacology technologies for personalization of cardiovascular diseases drug treatment: focus on direct oral anticoagulantsКлинико-фармакологические технологии персонализации фармакотерапии сердечно-сосудистых заболеваний: фокус на прямые оральные антикоагулянтыhttps://orcid.org/0000-0002-4496-368078013891354525-7556SychevDmitry A.СычевДмитрий Алексеевич
Russian Federation

MD, PhD, Professor

Член-корреспондент РАН, Доктор медицинских наук, профессор

dmitrysychevrmapo@gmail.comhttps://orcid.org/0000-0002-2970-34427282-6014SychevIgor N.СычевИгорь Николаевич
Russian Federation

MD, PhD

кандидат медицинских наук

sychevigor@mail.ruhttps://orcid.org/0000-0002-9307-4994571896436358308-7599MirzaevKarin B.МирзаевКарин Бадавиевич
Russian Federation

MD, PhD

кандидат медицинских наук

karin05doc@yandex.ruhttps://orcid.org/0000-0003-2511-0655571942027497095-1630RytkinEric I.РыткинЭрик Игоревич
Russian Federation

PhD Student

Аспирант кафедры клинической фармакологии и терапии

erytkin@gmail.comhttps://orcid.org/0000-0002-2295-7167566744707009435-7794IvashchenkoDmitriy V.ИващенкоДмитрий Владимирович
Russian Federation

MD, PhD

кандидат медицинских наук

dvi1991@yandex.ruhttps://orcid.org/0000-0003-2043-58483212-7905BureIrina V.БуреИрина Владимировна
Russian Federation

PhD

bureira@mail.ruhttps://orcid.org/0000-0003-0623-72638357-5770OtdelenovVitaliy A.ОтделеновВиталий Александрович
Russian Federation

PhD

кандидат медицинских наук

vitotd@ya.ruRussian Medical Academy of Continuous Professional EducationРоссийская медицинская академия непрерывного профессионального образования19112019041220197452993060410201928102019Copyright ©; 2019, "Paediatrician" Publishers LLCCopyright ©; 2019, Издательство "Педиатръ"2019"Paediatrician" Publishers LLCИздательство "Педиатръ"https://vestnikramn.spr-journal.ru/jour/about/submissionshttps://vestnikramn.spr-journal.ru/jour/article/view/1214

One of the main causes for adverse reactions development is not taking into account the pharmacokinetics of drugs and the dose. Pharmacokinetics of drugs is mostly defined by the cytochrome P-450 isoenzymes activity, carboxylesterases and many other isoenzymes of drug metabolism, as well as ADME transporters (P-gp etc.) which take part in the process of drug metabolism. The activity of these isoenzymes is defined by the genetic aspects of patients and non-genetic aspects such as comorbidity and drug-drug interactions. The development of complex algorithms for personalization of therapy based on the results of pharmacogenetic studies and in the form of a decision support system will play an important role in reduction of adverse drug reactions. A lot can be achieved for personalization of Direct Oral Anticoagulants for treatment of cardiovascular diseases. New approaches are being developed based on the results of pharmacogenetic and pharmacokinetic testing that will help diminish adverse effects of drugs.

Одной из важных причин развития ятрогенных лекарственных поражений внутренних органов является недоучет врачами при выборе лекарственных средств (ЛС) и их режимов дозирования индивидуальных особенностей фармакокинетики препаратов в организме пациента, которая во многом определяется активностью ферментативных систем биотрансформации ЛС (ферменты I фазы ― изоферменты цитохрома Р-450, карбоксиэстеразы и др., ферменты II фазы ― N-ацетилтрансфераза и др.) и активностью транспортеров, участвующих в процессах всасывания, распределения и выведения ЛС (Р-гликопротеин, транспортеры органических анионов и катионов). При этом активность этих систем зависит от генетических особенностей пациентов (полиморфизмы соответствующих генов ― предмет изучения фармакогенетики) и негенетических факторов, таких как сопутствующие заболевания и состояния, а также межлекарственных взаимодействий. С этих позиций разработка комплексных подходов к прогнозированию и профилактике развития ятрогенных лекарственных поражений внутренних органов с использованием как фармакогенетических (уже активно проводятся), так и фармакокинетических (мониторинг равновесных концентраций лекарств в биологических жидкостях, малоинвазивная оценка активности ферментативных систем, и прежде всего изоферментов цитохрома Р-450) исследований, которые будут доступны врачам (в т.ч. с помощью информационных технологий ― за счет разработки компьютеризированной системы поддержки принятия клинических решений), позволит им персонализировать применение лекарств, сводя к минимуму нежелательные лекарственные реакции и снижая тем самым инвалидизацию и смертность от них. Таким образом, актуальными представляются комплексные (фармакогенетические и фармакокинетические) подходы к прогнозированию и профилактике (на основе создания алгоритмов выбора ЛС и их режимов дозирования) ятрогенных лекарственных поражений внутренних органов у пациентов с социально значимыми заболеваниями.

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