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’)10.30895/2312-7821-2021-9-2-85-94safetyrisk-211Research ArticleОБЗОРЫREVIEWSЖенский пол как фактор риска развития лекарственно-индуцированных заболеванийFemale Gender as a Risk Factor for the Development of Drug-Induced Diseaseshttps://orcid.org/0000-0002-4496-3680СычевД. А.SychevD. A.

Дмитрий Алексеевич Сычев, д-р мед. наук, профессор, член-корр. РАН

ул. Баррикадная, д. 2/1, стр. 1, Москва, 125993

Dmitry A. Sychev, Dr. Sci. (Med.), Professor, Corr. Member of RAS

2/1/1 Barrikadnaya St., Moscow 125993

rmapo@rmapo.ruhttps://orcid.org/0000-0002-0795-8225ОстроумоваО. Д.OstroumovaO. D.

Остроумова Ольга Дмитриевна, д-р мед. наук, профессор

ул. Баррикадная, д. 2/1, стр. 1, Москва, 125993

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

Olga D. Ostroumova, Dr. Sci. (Med.), Professor

2/1/1 Barrikadnaya St., Moscow 125993

8/2 Trubeczkaya St., Moscow 2119991

ostroumova.olga@mail.ruhttps://orcid.org/0000-0001-7168-3636ПереверзевА. П.PereverzevA. P.

Переверзев Антон Павлович, канд. мед. наук

ул. Баррикадная, д. 2/1, стр. 1, Москва, 125993

Anton Р. Pereverzev, Cand. Sci. (Med.)

2/1/1 Barrikadnaya St., Moscow 125993

acchirurg@mail.ruhttps://orcid.org/0000-0001-5801-3742КочетковА. И.KochetkovA. I.

Кочетков Алексей Иванович, канд. мед. наук

ул. Баррикадная, д. 2/1, стр. 1, Москва, 125993

Aleksey I. Kochetkov, Cand. Sci. (Med.)

2/1/1 Barrikadnaya St., Moscow 125993

ak_info@list.ruhttps://orcid.org/0000-0003-1499-247XОстроумоваТ. М.OstroumovaT. M.

Остроумова Татьяна Максимовна, канд. мед. наук

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

Tatiana M. Ostroumova, Cand. Sci. (Med.)

8/2 Trubeczkaya St., Moscow 2119991

t.ostroumova3@gmail.comhttps://orcid.org/0000-0003-4258-1889КлепиковаМ. В.KlepikovaM. V.

Клепикова Мария Викторовна, канд. мед. наук

ул. Баррикадная, д. 2/1, стр. 1, Москва, 125993

Maria V. Klepikova, Cand. Sci. (Med.)

2/1/1 Barrikadnaya St., Moscow 125993

pelageam@yandex.ruhttps://orcid.org/0000-0001-6573-4169ЭбзееваЕ. Ю.EbzeevaE. Yu.

Эбзеева Елизавета Юрьевна, канд. мед. наук, доцент

ул. Баррикадная, д. 2/1, стр. 1, Москва, 125993

Elizaveta Yu. Ebzeeva, Cand. Sci. (Med.), Associate Professor

2/1/1 Barrikadnaya St., Moscow 125993

veta67@mail.ruФедеральное государственное бюджетное образовательное учреждение дополнительного профессионального образования «Российская медицинская академия непрерывного профессионального образования» Министерства здравоохранения Российской ФедерацииРоссияRussian Medical Academy of Continuous Professional EducationRussian FederationФедеральное государственное бюджетное образовательное учреждение дополнительного профессионального образования «Российская медицинская академия непрерывного профессионального образования» Министерства здравоохранения Российской Федерации; Федеральное государственное автономное образовательное учреждение высшего образования «Первый Московский государственный медицинский университет имени И. М. Сеченова» Министерства здравоохранения Российской ФедерацииРоссияRussian Medical Academy of Continuous Professional Education; I. M. Sechenov First Moscow State Medical UniversityRussian FederationФедеральное государственное автономное образовательное учреждение высшего образования «Первый Московский государственный медицинский университет имени И. М. Сеченова» Министерства здравоохранения Российской ФедерацииРоссияI. M. Sechenov First Moscow State Medical UniversityRussian Federation202130042021928594Copyright © Сычев Д.А., Остроумова О.Д., Переверзев А.П., Кочетков А.И., Остроумова Т.М., Клепикова М.В., Эбзеева Е.Ю., 20212021Сычев Д.А., Остроумова О.Д., Переверзев А.П., Кочетков А.И., Остроумова Т.М., Клепикова М.В., Эбзеева Е.Ю.Sychev D.A., Ostroumova O.D., Pereverzev A.P., Kochetkov A.I., Ostroumova T.M., Klepikova M.V., Ebzeeva E.Y.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/211

Половая принадлежность пациента является одним из значимых факторов, влияющих на риск развития нежелательных реакций при применении лекарственных препаратов. По данным научной литературы, риск развития лекарственно-индуцированных симптомов, синдромов и заболеваний у женщин в 1,5–1,7 раза выше, чем у мужчин. Цель работы: анализ и систематизация данных о причинах, обуславливающих повышенный риск развития лекарственно-индуцированных заболеваний у лиц женского пола. Показано, что более высокий риск развития осложнений фармакотерапии при применении некоторых групп лекарственных препаратов у женщин обусловлен совокупностью факторов, оказывающих влияние на фармакокинетику и фармакодинамику, таких как анатомофизиологические особенности организма, особенности активности/экспрессии ферментов и транспортных белков. Более высокое процентное содержание жировой ткани и более низкое содержание воды в женском организме по сравнению с мужским влияет на объем распределения липофильных препаратов, например опиоидов и бензодиазепинов, вызывая их накопление в организме. У женщин более низкая, чем у мужчин, скорость экскреции и элиминации лекарственных средств почками, что может способствовать развитию нежелательных реакций при применении препаратов, которые выводятся из организма преимущественно с мочой. Изменения гормонального фона при приеме женщинами препаратов половых стероидов с целью заместительной терапии или контрацепции, а также колебания уровня эндогенных половых стероидных гормонов во время менструального цикла, беременности и в перименопаузе за счет связанных с ними изменений объема распределения препарата, активности ферментов цитохрома Р450 и скорости клубочковой фильтрации также могут оказывать влияние на фармакокинетику и фармакодинамику других лекарственных препаратов, что, в свою очередь, отражается на безопасности фармакотерапии. Для повышения безопасности фармакотерапии у лиц женского пола при выборе схемы лечения, в том числе режима дозирования и пути введения лекарственного препарата, необходимо учитывать выявленные особенности фармакокинетики и фармакодинамики лекарственных препаратов у данной категории пациентов.

Gender is an important factor affecting the risk of drug-induced adverse reactions in patients. According to scientific literature, the risk of drug-induced symptoms, syndromes, and diseases is 1.5–1.7 times higher in women than in men. The aim of the study was to analyse and systematise data on the factors responsible for increased risk of drug-induced diseases in women. It was demonstrated that the increased risk of complications in women following the use of certain pharmacological classes of drugs is associated with a combination of factors that affect pharmacokinetics and pharmacodynamics. These factors include anatomical and physiological characteristics, specificity of enzyme and transport protein activity/expression. Women, compared to men, have higher percentage of adipose tissue and lower percentage of water in the body, which affects the volume of distribution of lipophilic agents, such as opioids and benzodiazepines, resulting in their accumulation in the body. Women have a lower rate of renal excretion and elimination, as compared to men, which may lead to adverse reactions following the use of medicines with predominantly urinary excretion. Changes in the endocrine profile in women taking sex steroids as replacement therapy or a contraceptive measure, as well as fluctuations in endogenous sex steroids during the menstrual cycle, pregnancy, perimenopause, influence the volume of distribution, the activity of cytochrome P450 enzymes, and the glomerular filtration rate, and, thus, may affect the pharmacokinetics and pharmacodynamics of other medicinal products, which, in turn, affect the safety of pharmacotherapy. In order to increase the safety of pharmacotherapy in women, it is necessary to consider the revealed specific pharmacokinetic and pharmacodynamic parameters of the medicine in a given group of patients when selecting the treatment regimen, including the dosage regimen and routes of administration.

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