Влияние метаболических нарушений на терапевтическую эффективность и токсичность амиодарона: механизмы и перспективы коррекции

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.

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