vedomostiregmedРегуляторные исследования и экспертиза лекарственных средствRegulatory Research and Medicine Evaluation3034-30623034-3453Federal State Budgetary Institution ‘Scientific Centre for Expert Evaluation of Medicinal Products’ of the Ministry of Health of the Russian Federation (FSBI ‘SCEEMP’)vedomostiregmed-105Research ArticleДОКЛИНИЧЕСКОЕ И КЛИНИЧЕСКОЕ ИЗУЧЕНИЕ ЛЕКАРСТВЕННЫХ СРЕДСТВPRECLINICAL AND CLINICAL STUDY OF MEDICINESФармакологическая регуляция активности изоферментов цитохромов P450 3A4 и P450 2C9 витаминами и природными соединениямиPharmacological regulation of the activity of cytochrome P450 3A4 AND P450 2C9 isoenzymes by vitamins and natural compoundsШихЕ. В.ShikhE. V.noemail@neicon.ruМаховаА. А.MakhovaA. A.noemail@neicon.ruШумянцеваВ. В.ShumyantsevaV. V.noemail@neicon.ruДемидоваО. А.DemidovaO. A.noemail@neicon.ruНаучный центр экспертизы средств медицинского примененияРоссияScientific Centre for Expert Evaluation of Medicinal ProductsRussian FederationПервый Московский государственный медицинский университет им. И. М. СеченоваРоссияI. M. Sechenov First Moscow State Medical UniversityRussian FederationНаучно-исследовательский институт биомедицинской химии им. В. Н. ОреховичаРоссияV. N. Orekhovich Scientific Research Institute of Biomedical ChemistryRussian Federation201613022018044247Copyright © Ших Е.В., Махова А.А., Шумянцева В.В., Демидова О.А., 20182018Ших Е.В., Махова А.А., Шумянцева В.В., Демидова О.А.Shikh E.V., Makhova A.A., Shumyantseva V.V., Demidova O.A.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.vedomostincesmp.ru/jour/article/view/105

Проведено исследование влияния витаминов, обладающих антиоксидантными свойствами (витамины A, E, C), витаминов группы B (B1, B2, B6), а также витаминоподобных веществ (коэнзим Q10, таурин и L-карнитин) на ферменты первой фазы метаболизма ксенобиотиков - цитохромы P450 3A4 и P450 2C9. В экспериментах с участием информированных добровольцев показано, что витамины группы В позволяют сократить длительность терапии нестероидным противовоспалительным препаратом диклофенака и снизить ежедневную потребность в нем. Показано также положительное влияние витаминов группы В на уменьшение болевого синдрома, позволяющее сократить длительность терапии и снизить ежедневную потребность в диклофенаке. Фармакодинамические и фармакокинетические данные подтверждены в экспериментах по исследованию электрокаталитической активности цитохрома P450 3A4 (CYP3A4) электрохимическими методами. Электрохимический подход для исследования каталитической активности цитохромов P450 и влияния витаминов и природных соединений на электрокатализ является чувствительным и эффективным сенсорным методом, позволяющим использовать низкие концентрации белка на электроде (до 10-15 моль/электрод), проводить анализ без участия белков-партнеров (цитохрома B5, НАДФН-зависимой редуктазы) и выявлять взаимодействие лекарственных препаратов в доклинических экспериментах. При сравнении влияния витаминов группы B (B1, B2, B6) в одинаковой концентрации (300 мкМ) по данным электрохимического анализа, рибофлавин (витамин B2) наиболее эффективно подавляет взаимодействие диклофенака с цитохромом P450 3A4. Витаминоподобное вещество таурин, обладающее антиоксидантными свойствами, и витамины-антиоксиданты стимулировали электрохимическое восстановление цитохромов P450 3A4 и P450 2C9. Полученные данные подтверждают возможность регуляции фармакокинетических параметров и выраженности фармакодинамического эффекта с помощью влияния витаминов на активность цитохромов P450 3A4 (CYP3A4) и P450 2C9 (CYP2C9).

The influence of vitamins with antioxidant properties (vitamins A, E, C), B vitamins (B1, B2, B6) and vitamin-like substances (coenzyme Q10, taurine and L-carnitine) on the enzymes of the first phase of xenobiotic metabolism - cytochromes P450 3A4 and P450 2C9 has been studied. The experiments with informed volunteers have shown that B vitamins can shorten the duration of nonsteroidal anti-inflammatory drug diclofenac therapy and reduce the daily need for it. The positive effect of B vitamins in reducing the pain syndrome, shortening the duration of therapy and reducing the need for daily intake of diclofenac. Pharmacodynamic and pharmacokinetic data have been confirmed by electrochemical tests of electrocatalytic activity of cytochrome P450 3A4 (CYP3A4). Electrochemical approach to the study of catalytic activity of cytochrome P450 and the impact of vitamins and natural compounds on electrocatalysis is an accurate and effective touch-sensitive method allowing to use low concentrations of protein at an electrode (10-15 mol/electrode), to conduct the analysis without using protein pairs (cytochrome B5, NADPH-dependent reductase) and to identify the interaction of drugs in preclinical studies. When comparing the influence of B vitamins (B1, B2, B6) in the same concentration (300 μM) according to the electrochemical analysis, riboflavin (vitamin B2) is most effectively inhibits the interaction of diclofenac with cytochrome P450 3A4. Vitamin-like substance taurine with antioxidant properties and antioxidant vitamins stimulated electrochemical reduction of cytochromes P450 3A4 and P450 2C9. The obtained data confirm that it is possible that the influence of vitamins on cytochromes P450 3A4 (CYP3A4) и P450 2C9 (CYP2C9) allows to regulate pharmacokinetic parameters and the pharmacodynamic effect intensity.

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