Омиксные биомаркеры эффективности и безопасности антипсихотиков: фокус на луразидон

Введение. Луразидон — атипичный антипсихотик с высоким сродством к 5-HT₂A-, 5-HT₇и DRD2-рецепторам, однако его применение ограничено межиндивидуальной вариабельностью фармакокинетики и дозозависимыми нежелательными явлениями. Мультиомиксные подходы открывают возможности для персонализированного дозирования.

Цель. Систематизировать данные о геномных, транскриптомных и эпигеномных биомаркерах, ассоциированных с эффективностью и безопасностью луразидона.

Методы. Проведён поиск в PubMed, Scopus и РИНЦ (2010–2026 гг.) по ключевым словам: lurasidone, pharmacogenomics, CYP3A4, HTR1A, microRNA, therapeutic drug monitoring. Из 187 идентифицированных публикаций после скрининга было отобрано 83 источника.

Результаты. Полиморфизм rs6295 гена HTR1A ассоциирован с эффективностью луразидона у европейцев с шизофренией. CYP3A4 — основной фермент метаболизма: CYP3A4*1G (rs2242480) значимо влияет на клиренс (CL/F: C/C — 330 л/ч, T/T — 441 л/ч); CYP3A4*15 требует коррекции дозы до 240 мг/сут у носителей. При печёночной недостаточности рекомендовано снижение до 20–40 мг/сут. Транскриптомные исследования выявили 1907 дифференциально экспрессирующихся генов, включая модуляцию PER1 и BMAL1, а также дисбаланс нейротрансмиттеров. МикроРНК (miR-181b, miR-21, miR-122) рассматриваются как перспективные биомаркеры ответа и активности CYP. Эффективность монотерапии при биполярной депрессии II типа не превышает 41,3 %.

Заключение. Наиболее клинически значимыми маркерами являются полиморфизмы CYP3A4 (rs2242480, CYP3A4*15) и HTR1A (rs6295), а также микроРНК. Требуются проспективные исследования для валидации мультиомиксных панелей в клинической практике.

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