Полиморфизмы генов цитохрома P450 и их влияние на фармакокинетику антипсихотиков при шизофрении: обзор

ВВЕДЕНИЕ. Активность ферментов системы цитохрома Р450 (CYP450), играющих ключевую роль в метаболизме антипсихотиков, оказывает влияние на эффективность и безопасность терапии шизофрении. Приоритетное значение для безопасности терапии имеет индивидуализация выбора препаратов и их дозы с использованием фармакогенетического тестирования.

ЦЕЛЬ. Систематизировать данные о влиянии полиморфизмов генов CYP2D6, CYP2C19, CYP1A2 и CYP3A4, кодирующих ферменты CYP450, на концентрацию антипсихотиков в плазме крови и риск нежелательных реакций для интеграции в персонализированные алгоритмы терапии.

ОБСУЖДЕНИЕ. Ключевыми факторами, определяющими эффективность и безопасность терапии антипсихотиками, являются различия в метаболизме, обусловленные полиморфизмами генов изоферментов CYP450: CYP2D6, CYP2C19, CYP1A2. Генотип пациента предопределяет фенотип метаболизма. В соответствии с уровнем активности ферментов системы CYP450 выделяют 4 основных типа метаболизаторов: медленный, промежуточный, нормальный (наиболее распространенный) и ультрабыстрый. Наиболее значимое влияние на стратегию назначения антипсихотиков, особенно второго и третьего поколений, оказывают крайние варианты метаболизаторов. Генотипы, носительство которых предопределяет скорость метаболизма, также ассоциированы с полом и этнической принадлежностью.

ВЫВОДЫ. Интеграция фармакогенетического тестирования (в первую очередь генотипирования CYP2D6) в клиническую практику позволяет оптимизировать выбор и дозирование антипсихотиков, повысить эффективность и безопасность терапии шизофрении, снизить экономические затраты. Рекомендуется проведение тестирования у пациентов с неудовлетворительным ответом на терапию, развитием нежелательных реакций или при планировании терапии клозапином/оланзапином (CYP1A2).

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