safetyriskБезопасность и риск фармакотерапииSafety and Risk of Pharmacotherapy2312-78212619-1164Federal State Budgetary Institution ‘Scientific Centre for Expert Evaluation of Medicinal Products’ of the Ministry of Health of the Russian Federation (FSBI ‘SCEEMP’)10.30895/2312-7821-2025-475safetyrisk-475Research ArticleГЛАВНАЯ ТЕМА: БЕЗОПАСНОСТЬ ПАЦИЕНТА: КАК ДОКЛИНИЧЕСКИЕ ДАННЫЕ И ПОСТРЕГИСТРАЦИОННЫЙ ФАРМАКОНАДЗОР ФОРМИРУЮТ СОВРЕМЕННЫЙ ЛАНДШАФТ ФАРМАКОТЕРАПИИMAIN TOPIC: PATIENT SAFETY: THE WAY PRECLINICAL DATA AND POST-AUTHORISATION PHARMACOVIGILANCE SHAPE MODERN PHARMACOTHERAPEUTIC LANDSCAPEОценка безопасности лекарственных средств в отношении сердечно-сосудистой системы в доклинических исследованиях in vivo: обзорCardiovascular Safety Assessment of Medicines in Preclinical In vivo Studies: A Reviewhttps://orcid.org/0000-0002-9846-8335СултановаК. Т.SultanovaK. T.

Султанова Кира Тимуровна, канд. мед. наук

ул. Заводская, д. 3, к. 245, Всеволожский район, г.п. Кузьмоловский, Ленинградская обл., 188663

Kira T. Sultanova, Cand. Sci. (Med.)

3/245 Zavodskaya St., Kuzmolovsky urban-type settlement, Vsevolozhsky district, Leningrad Region 188663

sultanova.kt@doclinika.ruhttps://orcid.org/0000-0002-9828-3242МирошниковМ. В.MiroshnikovM. V.

Мирошников Михаил Владимирович, канд. мед. наук

ул. Заводская, д. 3, к. 245, Всеволожский район, г.п. Кузьмоловский, Ленинградская обл., 188663

Mihail V. Miroshnikov, Cand. Sci. (Med.)

3/245 Zavodskaya St., Kuzmolovsky urban-type settlement, Vsevolozhsky district, Leningrad Region 188663

miroshnikov.mv@doclinika.ruhttps://orcid.org/0000-0002-5386-7551БородинаА. Ю.BorodinaA. Yu.

Бородина Антонина Юрьевна

ул. Заводская, д. 3, к. 245, Всеволожский район, г.п. Кузьмоловский, Ленинградская обл., 188663

Antonina Yu. Borodina

3/245 Zavodskaya St., Kuzmolovsky urban-type settlement, Vsevolozhsky district, Leningrad Region 188663

borodina.ay@doclinika.ruhttps://orcid.org/0000-0001-8379-0279СимоноваЕ. В.SimonovaE. V.

Симонова Елизавета Владимировна

ул. Заводская, д. 3, к. 245, Всеволожский район, г.п. Кузьмоловский, Ленинградская обл., 188663

Elizaveta V. Simonova

3/245 Zavodskaya St., Kuzmolovsky urban-type settlement, Vsevolozhsky district, Leningrad Region 188663

selizabiet98@mail.ruhttps://orcid.org/0000-0003-1299-0200УстенкоЖ. Ю.UstenkoZh. Yu.

Устенко Жанна Юрьевна, канд. вет. наук

ул. Заводская, д. 3, к. 245, Всеволожский район, г.п. Кузьмоловский, Ленинградская обл., 188663

Zhanna Yu. Ustenko, Cand. Sci. (Vet.)

3/245 Zavodskaya St., Kuzmolovsky urban-type settlement, Vsevolozhsky district, Leningrad Region 188663

ustenko.ju@doclinika.ruhttps://orcid.org/0000-0002-1448-921XМазукинаЕ. В.MazukinaE. V.

Мазукина Елизавета Владимировна

ул. Заводская, д. 3, к. 245, Всеволожский район, г.п. Кузьмоловский, Ленинградская обл., 188663

Elizaveta V. Mazukina

3/245 Zavodskaya St., Kuzmolovsky urban-type settlement, Vsevolozhsky district, Leningrad Region 188663

mazukina.ev@doclinika.ruhttps://orcid.org/0000-0003-1451-7716КрышеньК. Л.KryshenK. L.

Крышень Кирилл Леонидович, канд. биол. наук

ул. Заводская, д. 3, к. 245, Всеволожский район, г.п. Кузьмоловский, Ленинградская обл., 188663

Kirill L. Kryshen, Cand. Sci. (Biol.)

3/245 Zavodskaya St., Kuzmolovsky urban-type settlement, Vsevolozhsky district, Leningrad Region 188663

kryshen.kl@doclinika.ruhttps://orcid.org/0000-0001-7478-4942МатичинА. А.MatichinA. A.

Матичин Александр Алексеевич

ул. Заводская, д. 3, к. 245, Всеволожский район, г.п. Кузьмоловский, Ленинградская обл., 188663

Aleksandr A. Matichin

3/245 Zavodskaya St., Kuzmolovsky urban-type settlement, Vsevolozhsky district, Leningrad Region 188663

matichin.aa@doclinika.ruhttps://orcid.org/0000-0003-3176-6386МакароваМ. Н.MakarovaM. N.

Макарова Марина Николаевна, д-р мед. наук

ул. Заводская, д. 3, к. 245, Всеволожский район, г.п. Кузьмоловский, Ленинградская обл., 188663

Marina N. Makarova, Dr. Sci. (Med.)

3/245 Zavodskaya St., Kuzmolovsky urban-type settlement, Vsevolozhsky district, Leningrad Region 188663

makarova.mn@doclinika.ruhttps://orcid.org/0000-0002-2447-7888МакаровВ. Г.MakarovV. G.

Макаров Валерий Геннадьевич, д-р мед. наук, профессор

ул. Заводская, д. 3, к. 245, Всеволожский район, г.п. Кузьмоловский, Ленинградская обл., 188663

Valery G. Makarov, Dr. Sci. (Med.), Professor

3/245 Zavodskaya St., Kuzmolovsky urban-type settlement, Vsevolozhsky district, Leningrad Region 188663

makarov.vg@doclinika.ruАкционерное общество «Научно-производственное объединение «ДОМ ФАРМАЦИИ»РоссияResearch-and-manufacturing company “HOME OF PHARMACY”Russian Federation202529092025133263278Copyright © Султанова К.Т., Мирошников М.В., Бородина А.Ю., Симонова Е.В., Устенко Ж.Ю., Мазукина Е.В., Крышень К.Л., Матичин А.А., Макарова М.Н., Макаров В.Г., 20252025Султанова К.Т., Мирошников М.В., Бородина А.Ю., Симонова Е.В., Устенко Ж.Ю., Мазукина Е.В., Крышень К.Л., Матичин А.А., Макарова М.Н., Макаров В.Г.Sultanova K.T., Miroshnikov M.V., Borodina A.Y., Simonova E.V., Ustenko Z.Y., Mazukina E.V., Kryshen K.L., Matichin A.A., Makarova M.N., Makarov V.G.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/475ВВЕДЕНИЕ

ВВЕДЕНИЕ. Оценка безопасности лекарственных средств в отношении сердечно-сосудистой системы с использованием моделей in vivo является необходимым этапом доклинических исследований, которая проводится либо в исследованиях фармакологической безопасности, либо в рамках токсикологических исследований. В дизайне исследований фармакологической безопасности в первую очередь подразумевается оценка потенциала исследуемого вещества замедлять реполяризацию желудочков сердца без углубленного изучения возможного структурного повреждения сердца и сосудов. При этом в токсикологических исследованиях, как правило, не оцениваются электрофизиологические параметры. В нормативной документации Евразийского экономического союза и Международного совета по гармонизации (ICH) отсутствуют подробные указания по использованию специфических маркеров нарушений функционирования сердечно-сосудистой системы.

ЦЕЛЬ

ЦЕЛЬ. Разработка комплексного подхода по оценке кардио- и васкулотоксичности лекарственных препаратов в доклинических исследованиях in vivo.

ОБСУЖДЕНИЕ

ОБСУЖДЕНИЕ. Для оценки функционального состояния сердечно-сосудистой системы могут быть использованы как мелкие лабораторные животные (грызуны), так и более крупные, такие как кролики, хорьки, собаки, карликовые свиньи и приматы. Токсические эффекты изучаемых лекарственных препаратов в отношении сердца и сосудов у животных могут проявляться в виде изменений в физиологическом, биохимическом или структурном статусах систем или органов, поэтому оценка функционального состояния сердечно-сосудистой системы должна опираться на совокупность инструментальных, лабораторных и гистологических методов. В первую очередь применимы физиологические и лабораторные исследования. Рекомендовано проводить электрокардиографию, измерение частоты сердечных сокращений и артериального давления, а также количественно оценивать маркеры нарушения функций и структурного повреждения клеток. Для более глубокого анализа рекомендуется применять гистологические и иммуногистохимические исследования тканей сердца и сосудов, чтобы оценить изменения на тканевом и клеточном уровнях.

ВЫВОДЫ

ВЫВОДЫ. Эффективным способом обнаружения нарушений сердечно-сосудистой системы является применение комплексного подхода, который, с одной стороны, позволяет всесторонне оценить возможные токсические проявления лекарственного средства, а с другой — увеличивает трансляционной потенциал данных, получаемых на доклиническом этапе исследований.

INTRODUCTION

INTRODUCTION. The cardiovascular safety evaluation of medicines using in vivo models is a necessary preclinical step that is performed either in safety pharmacology studies or in toxicity studies. The design of safety pharmacology studies primarily involves assessing the potential of a test substance to prolong cardiac ventricular repolarisation, without in-depth investigation of potential structural damage to the heart and blood vessels. Toxicity studies usually do not include electrophysiological testing. The regulatory standards of the Eurasian Economic Union (EAEU) and the International Council for Harmonisation (ICH) lack detailed guidance on the use of specific markers of cardiovascular dysfunction.

AIM

AIM. This study aimed to develop an integrated approach to assessing the cardiac and vascular toxicity of medicinal products in preclinical in vivo studies.

DISCUSSION

DISCUSSION. Cardiovascular function can be assessed in both small laboratory animals (rodents) and larger animals, such as rabbits, ferrets, dogs, minipigs, and primates. The toxic effects of a test medicinal product on the cardiovascular system of animals may be manifested as physiological, biochemical, and structural changes in the systems and organs. Therefore, the assessment of cardiovascular function should be based on a combination of instrumental, laboratory, and histological methods. First of all, physiological and laboratory studies are applicable. It is recommended to perform electrocardiography, heart rate and blood pressure measurements, and quantification of markers of cardiovascular dysfunction and structural cell damage. For more in-depth analysis, histological and immunohistochemical studies of cardiac and vascular tissues are recommended to assess changes at the tissue and cellular levels.

CONCLUSIONS

CONCLUSIONS. An effective strategy for detecting cardiovascular disorders is the use of an integrated approach that, on the one hand, facilitates a comprehensive assessment of the possible toxic effects of a medicinal product and, on the other hand, increases the translational potential of the data obtained at the preclinical stage of research.

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