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’)10.30895/1991-2919-2019-9-3-162-166vedomostiregmed-235Research ArticleОБЗОРЫREVIEWSКлинико-фармакологические аспекты применения некоторых токолитических препаратов у беременных с угрозой преждевременных родовClinical Pharmacology Aspects of Some Tocolytic Drugs Used in Pregnant Women at Risk of Preterm Birthhttps://orcid.org/0000-0002-6389-2099СоковаЕ. А.SоkоvаE. A.

Сокова Елена Андреевна, канд. мед. наук, доцент

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

Elena A. Sokova, Cand. Sci. (Med.), Associate Professor

8/2 Petrovsky Blvd, Moscow 127051

sokova904@gmail.comhttps://orcid.org/0000-0001-6331-3109ЧиловаР. А.ChilovaR. A.

Чилова Раиса Алексеевна, д-р мед. наук, проф.

Трубецкая ул., д. 8, стр. 2, Москва, 119991

Raisa A. Chilova, Dr. Sci. (Med.), Professor

8/2 Trubetskaya St., Moscow 119991

https://orcid.org/0000-0003-0123-3044ДемидоваО. А.DemidovaO. A.

Демидова Ольга Александровна, канд. фарм. наук

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

Olga A. Demidova, Cand. Sci. (Pharm.)

8/2 Petrovsky Blvd, Moscow 127051

АкоповК. О.AkopovK. O.

Акопов Константин Олегович

Трубецкая ул., д. 8, стр. 2, Москва, 119991

Konstantin O. Akopov

8/2 Trubetskaya St., Moscow 119991

Федеральное государственное бюджетное учреждение «Научный центр экспертизы средств медицинского применения» Министерства здравоохранения Российской ФедерацииРоссияScientific Centre for Expert Evaluation of Medicinal ProductsRussian FederationФедеральное государственное автономное образовательное учреждение высшего образования «Первый Московский государственный медицинский университет им. И. М. Сеченова» Министерства здравоохранения Российской ФедерацииРоссияI. M. Sechenov First Moscow State Medical UniversityRussian Federation20192706201993162166Copyright © Сокова Е.А., Чилова Р.А., Демидова О.А., Акопов К.О., 20192019Сокова Е.А., Чилова Р.А., Демидова О.А., Акопов К.О.Sоkоvа E.A., Chilova R.A., Demidova O.A., Akopov K.O.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/235

Спонтанные преждевременные роды являются одной из актуальных проблем в акушерстве, поскольку продолжают оставаться основной причиной смертности и заболеваемости новорожденных во всем мире. Нерешенность вопросов этиологии, патогенеза и отсутствие лекарственных препаратов, применяемых по показаниям для лечения спонтанных преждевременных родов, обусловливает сложность проведения их рациональной фармакотерапии. С позиции клинической фармакологии проведен обзор данных научной литературы по проблеме рациональной фармакотерапии спонтанных преждевременных родов токолитическими лекарственными средствами — блокаторами медленных кальциевых каналов, ингибиторами циклооксигеназы. Приведены особенности фармакокинетики этих препаратов во время беременности. Обсуждаются фармакогенетические аспекты применения токолитиков у беременных женщин и их возможное клиническое значение. Показано, что существует значительная межиндивидуальная вариабельность концентрации нифедипина в плазме крови женщин с угрозой прерывания беременности в зависимости от генотипа CYP3A5. Продемонстрировано, что некоторые полиморфизмы CYP2C9 могут приводить к увеличению метаболического индекса, возрастанию клиренса индометацина и, соответственно, снижению его эффективности. В настоящее время рассматриваемый вопрос изучен недостаточно. Таким образом, необходимо дальнейшее исследование влияния различных генотипов CYP3A5 и CYP2C9 на эффективность и безопасность нифедипина и индометацина при их применении в акушерской практике как токолитиков.

Spontaneous preterm birth is one of the most pressing issues in obstetrics, as it remains one of the leading causes of newborn morbidity and mortality. Pending issues of aetiology, pathogenesis, and absence of medicinal products indicated for the treatment of spontaneous preterm labour pose a challenge for rational pharmacotherapy. The paper presents the results of a scientific literature review on the problem of rational pharmacotherapy of spontaneous preterm labour using tocolytic drugs — calcium channel blockers, cyclooxygenase inhibitors. The paper summarises specific pharmacokinetic parameters of these drugs during pregnancy. It discusses pharmacogenetic aspects of using tocolytic drugs in pregnant women and their potential clinical effects. It was demonstrated that women with threatened miscarriage had high interindividual variability in nifedipine plasma concentrations depending on CYP3A5 genotype. It was shown that certain genetic polymorphisms of CYP2C9 may lead to an increased metabolic rate and an increase in indomethacin clearance resulting in the reduction of its efficacy. Yet, there is minimal research regarding this issue. Therefore, further research is needed to assess the impact of CYP3A5 and CYP2C9 genotypes on the efficacy and safety of nifedipine and indomethacin used as tocolytic drugs in obstetrics.

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