phgenomicsФармакогенетика и фармакогеномикаPharmacogenetics and Pharmacogenomics2588-05272686-8849LLC "Izdatelstvo OKI"phgenomics-172Research ArticleАКТУАЛЬНЫЕ ОБЗОРЫCURRENT REVIEWИзучение активности изоферментов цитохрома Р450 для прогнозирования межлекарственных взаимодействий лекарственных средств в условиях полипрагмазииThe study of the activity of isoenzymes of cytochrome P450 for the prediction of drug-drug interactions of medicines in terms of polypharmacyСычёвД. А.SychevD. A.

г. Москва

Moscow

ОтделеновВ. А.OtdelenovV. A.

г. Москва

Moscow

ДенисенкоН. П.DenisenkoN. P.

г. Москва

Moscow

СмирновВ. В.SmirnovV. V.

г. Москва

Moscow

ФГБОУ ДПО Российская медицинская академия непрерывного профессионального образования Министерства здравоохранения Российской ФедерацииРоссияFSBEI FPE Russian Medical Academy of Continuous Professional Education of Ministry of Healthcare of the Russian FederationRussian FederationФГБОУ ДПО Российская медицинская академия непрерывного профессионального образования Министерства здравоохранения Российской ФедерацииРоссияFSBEI FPE Russian Medical Academy of Continuous Professional Education of Ministry of Healthcare of the Russian Federation,Russian FederationФГБОУ ВО Первый МГМУ им. И.М. Сеченова; Институт иммунологии ФМБА РоссииРоссияFirst Moscow State Medical University named after I.M. Sechenov; NRC Institute of Immunology FMBA of RussiaRussian Federation20162503202002411Copyright © Сычёв Д.А., Отделенов В.А., Денисенко Н.П., Смирнов В.В., 20202020Сычёв Д.А., Отделенов В.А., Денисенко Н.П., Смирнов В.В.Sychev D.A., Otdelenov V.A., Denisenko N.P., Smirnov V.V.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.pharmacogenetics-pharmacogenomics.ru/jour/article/view/172

Изоферменты цитохрома Р450 являются основными ферментами, катализирующими I фазу биотрансформации лекарственных средств, что, как правило, приводит к образованию гидрофильных и мало активных метаболитов. Наибольшую роль биотрансформации лекарственных средств играют CYP3A4, CYP2D6, CYP2C9, CYP2C19 и CYP1A2. Ингибирование и индукция изоферментов цитохрома Р450 под влиянием лекарственных средств является важным и клинически значимым механизмом фармакокинетического взаимодействия лекарственных средств. Изучение активности изоферментов цитохрома Р450 с помощью методов фенотипирования (определение концентраций их специфических субстратов и их метаболитов в биологических жидкостях) на фоне применения лекарственных средств позволяет предсказать неблагоприятные побочные реакции, возникающие в результате межлекарственных взаимодействий. Перспективным для клинической практики является использование для фенотипирования изоферментов цитохромов Р450 не экзогенных, а эндогенных субстратов (например, отношение кортизол/6-бета-гидроксикортизол в моче для оценки активности CYP3A4), что является максимально безопасным и малоинвазивным подходом для участников исследований.

Isozymes of cytochrome P450 enzymes are major catalyzing phase I biotransformation drugs that usually leads to the formation of hydrophilic and little active metabolites. The greatest role drugs play biotransformation CYP3A4, CYP2D6, CYP2C9, CYP2C19 and CYP1A2. Inhibition and induction of cytochrome P450 under the influence of drugs is an important and clinically relevant mechanism pharmacokinetics drug interactions. Study of the activity of isoenzymes of cytochrome P450 using phenotyping methods (determination of the concentration of specific substrates and metabolites thereof biological fluids) against application of drugs to predict adverse drug reactions resulting from drug-drug interactions. Promising for clinical practice is the use of phenotyping for the cytochrome P450 is not exogenous and endogenous substances (eg the ratio of cortisol / 6-beta-hydroxycortisol in urine to evaluate the activity of CYP3A4), which is the most safe and minimally invasive approach to research participants.

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