ВВЕДЕНИЕ

safetyrisk

Безопасность и риск фармакотерапии

Safety and Risk of Pharmacotherapy

2312-78212619-1164

Federal State Budgetary Institution ‘Scientific Centre for Expert Evaluation of Medicinal Products’ of the Ministry of Health of the Russian Federation (FSBI ‘SCEEMP’)

10.30895/2312-7821-2026-519

safetyrisk-519

Research Article

ГЛАВНАЯ ТЕМА: ПСИХОТРОПНАЯ ТЕРАПИЯ И ФАРМАКОНАДЗОР: РИСКИ НЕЖЕЛАТЕЛЬНЫХ РЕАКЦИЙ, МЕТОДЫ ИХ ВЫЯВЛЕНИЯ И ПУТИ ПЕРСОНАЛИЗАЦИИ

MAIN TOPIC: PSYCHOTROPIC THERAPY AND PHARMACOVIGILANCE: RISKS OF ADVERSE REACTIONS, DETECTION METHODS, AND APPROACHES OF PERSONALIZATION

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

Cytochrome P450 Gene Polymorphisms and Their Influence on Antipsychotic Pharmacokinetics in Schizophrenia: A Review

https://orcid.org/0009-0002-8990-9810

Жукова

М. О.

Zhukova

M. O.

Жукова Мария Олеговна

ул. Островитянова, д. 1, Москва, 117997

Maria O. Zhukova

1 Ostrovityanov St., Moscow 117997

mashavar04@mail.ru

https://orcid.org/0000-0003-1754-9051

Киселева

Н. М.

Kiseleva

N. M.

Киселева Нина Михайловна, д-р биол. наук, доцент

ул. Островитянова, д. 1, Москва, 117997

Nina M. Kiseleva, Dr. Sci. (Biol.), Associate Professor

1 Ostrovityanov St., Moscow 117997

kiseleva_nm@rsmu.ru

Институт фармации и медицинской химии федерального государственного автономного образовательного учреждения высшего образования «Российский национальный исследовательский медицинский университет имени Н.И. Пирогова» Министерства здравоохранения Российской ФедерацииРоссияInstitute of Pharmacy and Medicinal Chemistry, N.I. Pirogov Russian National Research Medical UniversityRussian Federation

2026

06072026

142168177

2026

Жукова М.О., Киселева Н.М.

Zhukova M.O., Kiseleva N.M.

Данная работа распространяется под лицензией Creative Commons Attribution 4.0.

This work is licensed under a Creative Commons Attribution 4.0 License.

https://www.risksafety.ru/jour/article/view/519

ВВЕДЕНИЕ

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

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

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

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).

INTRODUCTION

INTRODUCTION. The activity of cytochrome P450 enzymes (CYP450), which play a key role in antipsychotic metabolism, influences treatment efficacy and safety. Individualized drug selection and dosage using pharmacogenetic testing is crucial for treatment safety.

AIM

AIM. This review aimed to systematize data on the effects of polymorphisms of the CYP2D6, CYP2C19, CYP1A2, and CYP3A4 genes encoding CYP450 enzymes on antipsychotic plasma concentrations and the risk of adverse drug reactions, for integration into personalized treatment algorithms.

DISCUSSION

DISCUSSION. Key factors determining the efficacy and safety of antipsychotic therapy are differences in metabolism caused by polymorphisms in CYP450 isoenzyme genes: CYP2D6, CYP2C19, and CYP1A2. Patient genotype determines the metabolic phenotype. Based on the level of CYP450 activity, four major metabolizer phenotypes are distinguished: poor, intermediate, normal (most common), and ultrarapid metabolizers. The extreme metabolizer phenotypes have the most significant impact on antipsychotic prescribing strategies, particularly for second- and third-generation antipsychotics. Genotypes that determine metabolic rate are also associated with sex and ethnicity.

CONCLUSIONS

CONCLUSIONS. Integrating pharmacogenetic testing (primarily CYP2D6 genotyping) into clinical practice enables optimization of antipsychotic selection and dosing, enhances the efficacy and safety of schizophrenia treatment, and reduces healthcare costs. Testing is recommended for patients with an inadequate treatment response, those who develop adverse drug reactions, and when clozapine or olanzapine therapy is planned (CYP1A2).

антипсихотикиклозапинрисперидонцитохром Р450CYP450нежелательные реакциифармакогенетикашизофренияпродуктивные симптомыполиморфизмы геновCYP2D6CYP2C19CYP1A2CYP3A4безопасность лекарственных средств

antipsychoticsclozapinerisperidonecytochrome P450CYP450adverse drug reactionspharmacogeneticsschizophreniaproductive symptomsgene polymorphismsCYP2D6CYP2C19CYP1A2CYP3A4drug safety

Работа выполнена без спонсорской поддержки

The study was performed without external funding

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