gastro-jРоссийский журнал гастроэнтерологии, гепатологии, колопроктологииRussian Journal of Gastroenterology, Hepatology, Coloproctology1382-43762658-6673«Gastro» LLCgastro-j-1317Research ArticleЛЕКЦИИ И ОБЗОРЫLECTURES AND REVIEWSБезопасность пантопразола с позиций лекарственного взаимодействияPantoprazole – safety in drug-drug interactionШихЕ. В.ShikhE. V.СычевД. А.SychevD. A.ГБОУ ВПО «Первый Московский государственный медицинский университет им. И.М. Сеченова» Минздравсоцразвития РФРоссияState educational government-financed institution of higher professional education Sechenov First Moscow state medical university of the Russian federation Ministry of Health and Social DevelopmentRussian Federation201230092012225412Copyright © Ших Е.В., Сычев Д.А., 20122012Ших Е.В., Сычев Д.А.Shikh E.V., Sychev D.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.gastro-j.ru/jour/article/view/1317

Цель обзора. Провести сравнительный анализ путей метаболизма ингибиторов протонной помпы (ИПП) с целью выявления препарата с минимальной степенью влияния на активность изофермента цитохрома CYP2C19 для повышения безопасности проведения комбинированной терапии с лекарственными средствами, метаболизирующимися этим изоферментом.Основные положения. Пантопразол метаболизируется CYP2C19 и CYP3A4, однако из всех ИПП он обладает минимальной аффинностью к этим ферментам. Первичный метаболит пантопразола (4–гидроксипантопразол, образуемый под влиянием системы CYP) далее вступает во II фазу биотрансформации, которая заключается в конъюгации с сульфатом и протекает в цитозоле. II фаза биотрансформации пантопразола не зависит от системы цитохромов. Этим объясняют более низкую способность пантопразола, по сравнению с другими ИПП, к взаимодействию с лекарственными препаратами, метаболизирующимися CYP2C19 и CYP3A4.Подтверждением этого является относительная безопасность комбинации клопидогрела с пантопразолом у пациентов с заболеваниями сердечно-сосудистой системы, продемонстрированная в клинических наблюдениях последних лет.Заключение. Имеющиеся на сегодняшний день данные исследований in vitro и in vivo позволяют считать пантопразол (Нольпаза) наиболее безопасным для применения в комплексной терапии с целью минимизации нежелательных реакций, возникающих в результате межлекарственного взаимодействия.

The aim of review

The aim of review. To carry out comparative analysis of metabolic pathways of proton pump inhibitors (PPI), to determine the agent with lowest effect on activity of cytochrome CYP2C19 isoenzyme for improvement of safety of combined treatment by pharmaceuticals metabolized by this isoenzyme.

Key points

Key points. Pantoprazole is metabolized by CYP2C19 and CYP3A4, however, it has the lowest affinity to these enzymes of all PPIs. The primary metabolite of pantoprazole (the CYP system product 4-hydroxypantoprazole) enters next cytosolic phase of biotransformation i.e. conjugation to sulfate. Second phase of pantoprazole biotransformation does not depend on cytochrome system. It explains lower degree of interaction to CYP2C19 and CYP3A4-metabolized drugs for pantoprazole, in comparison to other PPIs. This is proved by relative safety of clopidogrel to pantoprazole combination in patients with cardio-vascular diseases, demonstrated in clinical studies of the last years.

Conclusion

Conclusion. Data of investigations, available for the present time, in vitro and in vivo allow to consider pantoprazole (Nolpaza) as the most safe drug for application in complex therapy to reduce the drug interaction-associated adverse effects.

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