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’)10.30895/1991-2919-2020-10-2-89-95vedomostiregmed-283Research ArticleОБЗОРЫREVIEWSТерапевтический лекарственный мониторинг, гено- и фенотипирование CYP2C9 при применении препаратов глибенкламида у больных сахарным диабетомTherapeutic Drug Monitoring, CYP2C9 Genotyping and Phenotyping in the Treatment of Diabetes with Glibenclamide Productshttps://orcid.org/0000-0002-7322-3323ГородецкаяГ. И.GorodetskayaG. I.

Городецкая Галина Ивановна.

Петровский б-р, д. 8, стр. 2, Москва, 127051

Galina I. Gorodetskaya

8/2 Petrovsky Blvd, Moscow 127051

gorodetskaya@expmed.ruhttps://orcid.org/0000-0002-1441-3418АрхиповВ. В.ArkhipovV. V.

Архипов Владимир Владимирович - доктор медицинских наук, профессор. 

Петровский б-р, д. 8, стр. 2, Москва, 127051

 

Vladimir V. Arkhipov - Dr. Sci. (Med.), Professor.

8/2 Petrovsky Blvd, Moscow 127051

arkhipov@expmed.ruhttps://orcid.org/0000-0002-8993-4808МельниковЕ. С.MelnikovE. S.

Мельников Евгений Сергеевич - кандидат фармацевтических наук. 

Evgeny S. Melnikov - Cand. Sci. (Pharm.).

8/2 Petrovsky Blvd, Moscow 127051

evgueniy.melnikov@gmail.comhttps://orcid.org/0000-0002-0528-3068РодинаТ. А.RodinaT. A.

Родина Татьяна Александровна - кандидат химических наук. 

Tatiana A. Rodina - Cand. Sci. (Chem.).

8/2 Petrovsky Blvd, Moscow 127051

semina_tatiana@mail.ruФедеральное государственное бюджетное учреждение «Научный центр экспертизы средств медицинского применения» Министерства здравоохранения Российской ФедерацииРоссияScientific Centre for Expert Evaluation of Medicinal ProductsRussian Federation2020210620201028995Copyright © Городецкая Г.И., Архипов В.В., Мельников Е.С., Родина Т.А., 20202020Городецкая Г.И., Архипов В.В., Мельников Е.С., Родина Т.А.Gorodetskaya G.I., Arkhipov V.V., Melnikov E.S., Rodina T.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/283

Вопросы рационального применения препаратов глибенкламида при лечении больных сахарным диабетом 2 типа продолжают оставаться актуальными. В статье представлена обобщенная характеристика основных групп препаратов глибенкламида, рассмотрены особенности его фармакогенетики. Глибенкламид метаболизируется ферментом цитохрома P450 2C9 (CYP2C9), лица с генетически обусловленной низкой активностью CYP2C9 подвержены повышенному риску гипогликемии. Носители аллелей CYP2C9*3 и CYP2C9*2 склонны к более высокой концентрации глибенкламида в крови и повышенной секреции инсулина. Для снижения риска гипогликемии при терапии глибен-кламидом могут быть использованы фармакогенетическое тестирование и мониторинг концентрации лекарственных препаратов у пациентов с помощью ВЭЖХ-МС. На основании анализа данных литературы выбрана методика, которая отличается простотой пробоподготовки, коротким временем анализа и широким аналитическим диапазоном для определяемых веществ. Данная методика может быть полезной как для изучения биоэквивалентности, так и для оценки взаимозаменяемости препаратов глибенкламида. Фармакокинетика глибенкламида характеризуется высокой межиндивидуальной вариабельностью. Это является фактором как повышенного риска гипогликемии, так и неэффективности препарата, поэтому при назначении глибенкламида врач должен внимательно следить за эффективностью и безопасностью терапии.

Rational use of glybenclamide products in the treatment of patients with type 2 diabetes remains a high-priority task. The paper offers a summary of the main groups of glibenclamide drugs and describes pharmacogenetics of glybenclamide. Glibenclamide is metabolized by the enzyme cytochrome P450 2C9 (CYP2C9). Individuals with genetically determined low CYP2C9 activity are at an increased risk of hypoglycaemia. Carriers of CYP2C9*3 and CYP2C9*2 alleles tend to have higher concentrations of glybenclamide in blood and increased insulin secretion. Pharmacogenetic testing of patients and drug concentration monitoring using HPLC-MS can help reduce the risk of hypoglycemia during glibenclamide treatment. Based on literature review the authors selected the method characterised by a simple sample preparation procedure, short analysis time, and a wide analytical range for the substances being determined. This method can be useful both for bioequivalence studies and evaluation of glibenclamide products interchangeability. Glibenclamide pharmacokinetics is characterised by high interindividual variability. This may lead to both an increased risk of hypoglycemia and drug inefficacy, therefore, when prescribing glibenclamide, a physician should carefully control the efficacy and safety of drug therapy.

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