sibmedСибирский научный медицинский журналСибирский научный медицинский журнал2410-25122410-2520ИЦиГ СО РАН10.18699/SSMJ20250508sibmed-2440Research ArticleОБЗОРЫREVIEWSВлияние метаболических нарушений на терапевтическую эффективность и токсичность амиодарона: механизмы и перспективы коррекцииThe impact of metabolic disorders on the therapeutic efficacy and toxicity of amiodarone: mechanisms and management strategieshttps://orcid.org/0000-0001-8373-6109КозловЕ. Д.KozlovE. D.

Козлов Евгений Дмитриевич

430005, г. Саранск, ул. Большевистская, 68

Evgeniy D. Kozlov

430005, Saransk, Bolshevistskaya st., 68

dr.kozlov@yandex.ruhttps://orcid.org/0000-0003-1122-9532ЗорькинаА. В.ZorkinaA. V.

Зорькина Ангелина Владимировна, д.м.н., проф.

430005, г. Саранск, ул. Большевистская, 68

Angelina V. Zorkina, doctor of medical science, professor

430005, Saransk, Bolshevistskaya st., 68

wind-lina@mail.ruМордовский государственный университет им. Н.П. ОгареваРоссияOgarev Mordovia State UniversityRussian Federation20250411202545591110Copyright © Козлов Е.Д., Зорькина А.В., 20252025Козлов Е.Д., Зорькина А.В.Kozlov E.D., Zorkina A.V.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://sibmed.elpub.ru/jour/article/view/2440

Амиодарон является одним из наиболее эффективных и часто назначаемых антиаритмических препаратов класса III. Однако его фармакокинетика может нарушаться, а токсичность ‒ усугубляться при метаболических нарушениях. В обзоре представлены данные о том, что дислипидемия, ожирение и сахарный диабет 2 типа существенно влияют на фармакокинетику, фармакодинамику и токсический профиль амиодарона. Эти состояния изменяют связывание препарата с липопротеинами, активность цитохром P450-зависимых монооксигеназ и тканевое распределение, повышая риск кумуляции и токсических эффектов. Хроническая сердечная недостаточность усугубляет нарушение метаболизма и способствует мультисистемной токсичности. Современные клинические рекомендации не учитывают данные аспекты. Поэтому предложено более тщательно контролировать состояние данных пациентов и концентрацию препарата в плазме их крови (на индивидуальной основе), а также, в целом, назначать амиодарон с осторожностью. Перспективные направления включают проспективные клинические исследования амиодарона, математическое моделирование его фармакокинетики для персонализированного дозирования с учетом индекса массы тела, липидного профиля, коморбидной патологии, фармакогенетики (полиморфизмы цитохрома P450), а также поиск биомаркеров токсичности препарата.

Amiodarone is one of the most effective and commonly prescribed class III antiarrhythmic agents. However, its pharmacokinetics may be impaired and toxicity may be aggravated by metabolic disorders. The review presents data showing that dyslipidemia, obesity, and type 2 diabetes mellitus significantly affect pharmacokinetics, pharmacodynamics and toxic profile of amiodarone. These conditions alter the drug’s binding to lipoproteins, the activity of cytochrome P450- dependent monooxygenases and tissue distribution, thereby increasing the risk of accumulation and toxic effects. Chronic heart failure further impairs drug metabolism and contributes to multisystem toxicity. The current clinical guidelines do not adequately address these critical aspects. Therefore, more rigorous monitoring of these patients and their plasma drug concentration (on individual basis) is suggested, along with a generally more cautious approach to amiodarone use. Future perspectives include prospective clinical trials on amiodarone, physiologically based pharmacokinetic modeling for personalized dosing, based on body mass index, lipid profile, and comorbidities, pharmacogenomic studies (cytochrome P450 polymorphisms), as well as biomarker discovery for drug toxicity prediction.

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