akusherstvoObstetrics, Gynecology and ReproductionАкушерство, Гинекология и Репродукция2313-73472500-3194IRBIS LLC10.17749/2313-7347.2019.13.2.164-173akusherstvo-565Research ArticleREVIEW ARTICLESНАУЧНЫЕ ОБЗОРЫRole of P-glycoprotein in the pharmacotherapy of pregnant womenРоль гликопротеина-Р в фармакотерапии беременныхhttps://orcid.org/0000-0002-5166-8372ПоповаН. М.PopovaN. M.

Попова Наталья Михайловна – к.м.н., старший преподаватель кафедры фармакологии с курсом фармации ФДПО

Natalya M. Popova – PhD, Senior Lecturer, Department of Pharmacology with Course of Pharmacy, Faculty of Continuous Professional Education

p34-66@yandex.ruhttps://orcid.org/0000-0003-1688-0017ЩулькинА. В.ShchulkinA. V.

Щулькин Алексей Владимирович – к.м.н., доцент кафедры фармакологии с курсом фармации ФДПО

Alexey V. Shchulkin – PhD, Associate Professor, Department of Pharmacology with Course of Pharmacy, Faculty of Continuous Professional Education

https://orcid.org/0000-0002-5618-7607ЧерныхИ. В.ChernykhI. V.

Черных Иван Владимирович – к.б.н., ассистент кафедры общей и фармацевтической химии

Ivan V. Chernykh – PhD (Biology), Assistant, Department of General and Pharmaceutical Chemistry

https://orcid.org/0000-0002-3984-8979ЕсенинаА. С.EseninaA. S.

Есенина Анна Сергеевна – студент

Anna S. Esenina – Medical Student

https://orcid.org/0000-0002-2246-4127ГрадинарьМ. М.GradinarM. M.

Градинарь Мария Михайловна – студент

Maria M. Gradinar – Medical Student

https://orcid.org/0000-0001-6887-4888ЯкушеваЕ. Н.YakushevaE. N.

Якушева Елена Николаевна – д.м.н., профессор, зав. кафедрой фармакологии с курсом фармации ФДПО

Elena N. Yakusheva – MD, PhD, Professor, Head of Department of Pharmacology with Course of Pharmacy, Faculty of Continuous Professional Education,

ФГБОУ ВО «Рязанский государственный медицинский университет имени академика И.П. Павлова» Министерства здравоохранения Российской ФедерацииРоссияRyazan State Medical University named after Аcademician I.P. Pavlov, Health Ministry of Russian FederationRussian Federation201904072019132164173Copyright © Popova N.M., Shchulkin A.V., Chernykh I.V., Esenina A.S., Gradinar M.M., Yakusheva E.N., 20192019Попова Н.М., Щулькин А.В., Черных И.В., Есенина А.С., Градинарь М.М., Якушева Е.Н.Popova N.M., Shchulkin A.V., Chernykh I.V., Esenina A.S., Gradinar M.M., Yakusheva E.N.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.gynecology.su/jour/article/view/565

This review addresses the function of the protein-transporter glycoprotein-P (Pgp, ABCB1 protein) and the expression of its encoding gene MDR1/mdr1 throughout the gestational period in humans and animals. We discuss the relationship between the transporter function and the hormone fluctuations during pregnancy. We cite studies on the association between the MDR1/mdr1 gene polymorphisms and the hemato-placental barrier permeability for Pgp substrates, as well as fetal malformations. Under a separate section, drugs commonly used in pregnant women are characterized in terms of their roles as substrates, inducers or inhibitors of the Pgp transporter.

В статье представлены результаты исследований функциональной активности белка-транспортера гликопротеина-Р (Рgp, ABCB1-белок) и экспрессии гена MDR1/mdr1, кодирующего его, на протяжении гестационного срока у различных видов животных и человека. Показана связь функционирования транспортера с изменениями уровней гормонов при беременности. Приведены результаты исследований, свидетельствующих о влиянии полиморфизмов гена MDR1/mdr1 на проницаемость гематоплацентарного барьера для субстратов Pgp и формирование пороков развития плода. Отдельный раздел посвящен анализу принадлежности лекарственных препаратов, наиболее часто используемых в фармакотерапии беременных, к субстратам, индукторам и ингибиторам транспортера.

гликопротеин-P (Pgp)АВСВ1-транспортерген MDR1беременностьфармакотерапиясубстратыиндукторыингибиторыP-glycoprotein (Pgp)ABCB1 transporterMDR1 genepregnancypharmacotherapysubstratesinducersinhibitorsРабота поддержана грантом Российского фонда фундаментальных исследований № А18-015-00259.The study was supported by the Russian Foundation for Вasic Research, grant № А18-015-00259.ReferencesЖуравлева Е.О., Вельц Н.Ю., Затолочина К.Э. и др. Анализ спонтанных сообщений о нежелательных реакциях, развившихся при применении лекарственных средств во время беременности. Безопасность и риск фармакотерапии. 2017;5(2):61–9.Zhuravleva E.O., Velts N.Yu., Zatolochina K.E. et al. Analysis of spontaneous reports of adverse reactions that have developed with the use of drugs during pregnancy. [Analiz spontannyh soobshchenij o nezhelatel'nyh reakciyah, razvivshihsya pri primenenii lekarstvennyh sredstv vo vremya beremennosti]. Bezopasnost' i risk farmakoterapii. 2017;5(2):61–9. (In Russ.).Радзинский В.Е., Точиев Г.Ф. Полипрагмазия в лечении беременных женщин. Фарматека. 2011;13:10–1.Radzinsky V.E., Tochiev G.F. Polypragmasy in the treatment of pregnant women. [Polipragmaziya v lechenii beremennyh zhenshchin]. Farmateka. 2011;13:10–1. (In Russ.).Adam M.P., Polifka J.E., Friedman J.M. Evolving knowledge of the teratogenicity of medications in human pregnancy. Am J Med Genet C Semin Med Genet. 2011;157(3):175–82. DOI: 10.1002/ajmg.c.30313.Adam M.P., Polifka J.E., Friedman J.M. Evolving knowledge of the teratogenicity of medications in human pregnancy. Am J Med Genet C Semin Med Genet. 2011;157(3):175–82. DOI: 10.1002/ajmg.c.30313.Стриженок Е.А., Гудков И.В., Страчунский Л.С. Применение лекарственных средств при беременности: результаты многоцентрового фармакоэпидемиологического исследования. Клиническая микробиология и антимикробная химиотерапия. 2017;9(2):162–75.Strizhenok E.A., Gudkov I.V., Strachunskiy L.S. The use of drugs in pregnancy: the results of a multicenter pharmacoepidemiological study. [Primenenie lekarstvennyh sredstv pri beremennosti: rezul'taty mnogocentrovogo farmakoepidemiologicheskogo issledovaniya]. Klinicheskaya mikrobiologiya i antimikrobnaya himioterapiya. 2017;9(2):162–75. (In Russ.).Шер С.А. Тератогенное воздействие лекарственных средств на организм будущего ребенка на этапе внутриутробного развития. Педиатрическая фармакология. 2011;8(6):57–9.Sher S.A. Teratogenic effects of medicines on the future child's organism at the stage of intrauterine development. [Teratogennoe vozdejstvie lekarstvennyh sredstv na organizm budushchego rebenka na etape vnutriutrobnogo razvitiya]. Pediatricheskaya farmakologiya. 2011;8(6):57–9. (In Russ.).Стецюк О.У., Андреева И.В. Применение макролидов при беременности и лактации. Клиническая микробиология и антимикробная химиотерапия. 2010;12(1):41–53.Stetsyuk O.U., Andreeva I.V. Emerging concepts in use of macrolides in pregnancy and lactation. [Primenenie makrolidov pri beremennosti i laktacii]. Klinicheskaya mikrobiologiya i antimikrobnaya himioterapiya. 2010;12(1):41–53. (In Russ.).Гацанога М.В., Черных И.В., Щулькин А.В. и др. Можно ли оценивать принадлежность лекарственных веществ к субстратам гликопротеина-P на самках кроликов породы шиншилла. Наука молодых (Eruditio Juvenium). 2016;(3):5–10.Gatsanoga M.V., Chernykh I.V., Shchulkin A.V. et al. The method of assessment of drugs belonging to the substrates of P- glycoprotein on female rabbits. [Mozhno li ocenivat' prinadlezhnost' lekarstvennyh veshchestv k substratam glikoproteina-P na samkah krolikov porody shinshilla]. Nauka molodyh (Eruditio Juvenium). 2016;(3):5–10. (In Russ.).Якушева Е.Н., Черных И.В., Щулькин А.В., Попова Н.М. Гликопротеин-Р: структура, физиологическая роль и молекулярные механизмы модуляции функциональной активности. Успехи физиологических наук. 2014;45(4):89–98.Yakusheva E.N., Chernykh I.V., Shchulkin A.V., Popova N.M. P-glycoprotein: structure, physiological role and molecular mechanisms of modulation functional activity. [Glikoprotein-P: struktura, fiziologicheskaya rol' i molekulyarnye mekhanizmy modulyacii funkcional'noj aktivnosti]. Uspekhi fiziologicheskih nauk. 2014;45(4):89–98. (In Russ.).Enders A.C., Blankenship T.N. Comparative placental structure. Adv Drug Deliv Rev. 1999;38(1):3–15.Enders A.C., Blankenship T.N. Comparative placental structure. Adv Drug Deliv Rev. 1999;38(1):3–15.Zhang H., Wu X., Wang H. et al. Effect of pregnancy on cytochrome P450 3a and P-glycoprotein expression and activity in the mouse: mechanisms, tissue specificity, and time course. Mol Pharmacol. 2008;74(3):714–23.Zhang H., Wu X., Wang H. et al. Effect of pregnancy on cytochrome P450 3a and P-glycoprotein expression and activity in the mouse: mechanisms, tissue specificity, and time course. Mol Pharmacol. 2008;74(3):714–23.Kalabis G.M., Kostaki A., Andrews M.H. et al. Multidrug resistance phosphoglycoprotein (ABCB1) in the mouse placenta: fetal protection. Biol Reprod. 2005;73:591–7.Kalabis G.M., Kostaki A., Andrews M.H. et al. Multidrug resistance phosphoglycoprotein (ABCB1) in the mouse placenta: fetal protection. Biol Reprod. 2005;73:591–7.Ceckova-Novotna M., Pavek P., Staud F. P-glycoprotein in the placenta: expression, localization, regulation and function. Reprod Toxicol. 2006;22(3):400–10.Ceckova-Novotna M., Pavek P., Staud F. P-glycoprotein in the placenta: expression, localization, regulation and function. Reprod Toxicol. 2006;22(3):400–10.Chung F.S., Eyall S., Muzi M. et al. Positron emission tomography imaging of tissue P-glycoprotein activity during pregnancy in the non-human primate. Вr J Pharmacol. 2010;159:394–404.Chung F.S., Eyall S., Muzi M. et al. Positron emission tomography imaging of tissue P-glycoprotein activity during pregnancy in the non-human primate. Вr J Pharmacol. 2010;159:394–404.Gil S., Saura R., Forestier F., Farinotti R. P-glycoprotein expression of the human placenta during pregnancy. Placenta. 2005;26:268–70.Gil S., Saura R., Forestier F., Farinotti R. P-glycoprotein expression of the human placenta during pregnancy. Placenta. 2005;26:268–70.Mathias A.A., Hitti J., Unadkat J.D. P-glycoprotein and breast cancer resistance protein expression in human placentae of various gestational ages. Am J Physiol Regul Integr Comp Physiol. 2005;289(4):R963–9.Mathias A.A., Hitti J., Unadkat J.D. P-glycoprotein and breast cancer resistance protein expression in human placentae of various gestational ages. Am J Physiol Regul Integr Comp Physiol. 2005;289(4):R963–9.Yang C.P., DePinho S.G., Greenberger L.M. et al. Progesterone interacts with P-glycoprotein in multidrug-resistant cells and in the endometrium of gravid uterus. J Biol Chem. 1989;264(2):782–8.Yang C.P., DePinho S.G., Greenberger L.M. et al. Progesterone interacts with P-glycoprotein in multidrug-resistant cells and in the endometrium of gravid uterus. J Biol Chem. 1989;264(2):782–8.Huang Q.T., Shynlova O., Kibschull M. et al. P-glycoprotein expression and localization in the rat uterus throughout gestation and labor. Reproduction. 2016;152(3):195–204.Huang Q.T., Shynlova O., Kibschull M. et al. P-glycoprotein expression and localization in the rat uterus throughout gestation and labor. Reproduction. 2016;152(3):195–204.Arceci R.J., Baas F., Raponi R.et al. Multidrug resistance gene expression is controlled by steroid hormones in the secretory epithelium of the uterus. Mol Reprod Develop. 1990;25:101–9.Arceci R.J., Baas F., Raponi R.et al. Multidrug resistance gene expression is controlled by steroid hormones in the secretory epithelium of the uterus. Mol Reprod Develop. 1990;25:101–9.Попова Н.М., Щулькин А.В., Черных И.В. и др. Функциональная активность гликопротеина-P у кроликов породы «Советская шиншилла» при беременности. Российский медико-биологический вестник им. aкад. И.П. Павлова. 2018;26(4):466–73.Popova N.M., Shchulkin A.V., Chernykh I.V. et al. P-glycoprotein functional activity in “Soviet Chinchilla” rabbits during pregnancy. [Funkcional'naya aktivnost' glikoproteina-P u krolikov porody «Sovetskaya shinshilla» pri beremennosti]. Rossijskij medikobiologicheskij vestnik im. akad. I.P. Pavlova. 2018;26(4):466–73. (In Russ.).Щулькин А.В., Черных И.В., Якушева Е.Н. и др. Влияние эстрадиола на функционирование ABCB1-белка в эксперименте. Вестник Уральской медицинской академической науки. 2017;14(4):427–34.Shchulkin A.V., Chernykh I.V., Yakusheva E.N. et al. Estradiol influence on functioning of ABCB1-protein in experiment. [Vliyanie estradiola na funkcionirovanie ABCB1-belka v eksperimente]. Vestnik Ural'skoj medicinskoj akademicheskoj nauki. 2017;14(4):427–34. (In Russ.).Щулькин А.В., Черных И.В., Якушева Е.Н. и др. Влияние прогестерона на функциональную активность гликопротеина-P в эксперименте. Химико-фармацевтический журнал. 2017;52(6):102–7.Shchulkin A.V., Chernykh I.V., Yakusheva E.N. et al. Progesterone influence on functional activity of glycoprotein-P in experiment. [Vliyanie progesterona na funkcional'nuyu aktivnost' glikoproteina-P v eksperimente]. Himiko-farmacevticheskij zhurnal. 2017;52(6):102–7. (In Russ.).Щулькин А.В., Якушева Е.Н., Черных И.В. и др. Влияние тестостерона на функциональную активность гликопротеина-P. Химико-фармацевтический журнал. 2017;51(9):3–7.Shchulkin A.V., Yakusheva E.N., Chernykh I.V. et al. Testosterone influence on functional activity of glycoprotein-P. [Vliyanie testosterona na funkcional'nuyu aktivnost' glikoproteina-P]. Himiko-farmacevticheskij zhurnal. 2017;51(9):3–7. (In Russ.).Lankas G.R., Wise L.D., Cartwright M.E. et al. Placental P-glycoprotein deficiency enhances susceptibility to chemically induced birth defects in mice. Reprod Toxicol. 1998;12:457–63.Lankas G.R., Wise L.D., Cartwright M.E. et al. Placental P-glycoprotein deficiency enhances susceptibility to chemically induced birth defects in mice. Reprod Toxicol. 1998;12:457–63.Smit J.W., Huisman M.T., van Tellingen O. et al. Absence or pharmacological blocking of placental P-glycoprotein profoundly increases fetal drug exposure. J Clin Invest. 1999;104:1441–7.Smit J.W., Huisman M.T., van Tellingen O. et al. Absence or pharmacological blocking of placental P-glycoprotein profoundly increases fetal drug exposure. J Clin Invest. 1999;104:1441–7.Hitzl M., Schaeffeler E., Hocher B. et al. Variable expression of P-glycoprotein in the human placenta and its association with mutations of the multidrug resistance 1 gene (MDR1, ABCB1). Pharmacogenetics. 2004;14:309–18.Hitzl M., Schaeffeler E., Hocher B. et al. Variable expression of P-glycoprotein in the human placenta and its association with mutations of the multidrug resistance 1 gene (MDR1, ABCB1). Pharmacogenetics. 2004;14:309–18.Tanabe M., Ieiri I., Nagata N. et al. Expression of P-glycoprotein in human placenta: relation to genetic polymorphism of the multidrug resistance (MDR)-1 gene. J Pharmacol Exp Ther. 2001;297(3):1137–43.Tanabe M., Ieiri I., Nagata N. et al. Expression of P-glycoprotein in human placenta: relation to genetic polymorphism of the multidrug resistance (MDR)-1 gene. J Pharmacol Exp Ther. 2001;297(3):1137–43.Obermann-Borst S.A., Isaacs A., Younes Z. et al. General maternal medication use, folic acid, the MDR1 C3435T polymorphism, and the risk of a child with a congenital heart defect. Am J Obstet Gynecol. 2011;204(3):236.e1–e8.Obermann-Borst S.A., Isaacs A., Younes Z. et al. General maternal medication use, folic acid, the MDR1 C3435T polymorphism, and the risk of a child with a congenital heart defect. Am J Obstet Gynecol. 2011;204(3):236.e1–e8.Bliek B.J.B., van Schaik R.H.N., van der Heiden I.P. et al. Maternal medication use, carriership of the ABCB1 3435C > T polymorphism and the risk of a child with clef lip with or without cleft palate. Am J Med Genet A. 2009;149A(10):2088–92.Bliek B.J.B., van Schaik R.H.N., van der Heiden I.P. et al. Maternal medication use, carriership of the ABCB1 3435C > T polymorphism and the risk of a child with clef lip with or without cleft palate. Am J Med Genet A. 2009;149A(10):2088–92.Li J., Wang Z., Chen Y.P. et al. Association of fetal but not maternal P-glycoprotein C3435T polymorphism with fetal growth and birth weight, a possible risk factor for cardiovascular diseases in later life. Clin Lab. 2012;58:1085–9.Li J., Wang Z., Chen Y.P. et al. Association of fetal but not maternal P-glycoprotein C3435T polymorphism with fetal growth and birth weight, a possible risk factor for cardiovascular diseases in later life. Clin Lab. 2012;58:1085–9.Сокова Е.А., Кукес В.Г. Значение изучения полиморфизма гена ABCB1, кодирующего гликопротеин-Р, для оценки отношения ожидаемой пользы к возможному риску применения бетаадреноблокаторов у русских беременных с хронической артериальной гипертензией. Биомедицина. 2014;(2):119–27.Sokova E.A., Kukes V.G. The significance of ABCB1 gene C3435T polymorphism study for the evaluation of benefit/risk beta-blockers treatment in Russian pregnant women with chronic hypertension. [Znachenie izucheniya polimorfizma gena ABCB1, kodiruyushchego glikoprotein-R, dlya ocenki otnosheniya ozhidaemoj pol'zy k vozmozhnomu risku primeneniya beta-adrenoblokatorov u russkih beremennyh s hronicheskoj arterial'noj gipertenziej]. Biomedicina. 2014;(2):119–27. (In Russ.).Диагностика и лечение сердечно-сосудистых заболеваний при беременности: Российские рекомендации, 2013. Российский кардиологический журнал. 2013;(4, приложение 1):1–40. Режим доступа: http://www.scardio.ru/content/Guidelines/ beremennie_rek_2013.pdf.Diagnosis and treatment of cardiovascular diseases during pregnancy: Russian recommendations, 2013. [Diagnostika i lechenie serdechnososudistyh zabolevanij pri beremennosti: Rossijskie rekomendacii, 2013]. Rossijskij kardiologicheskij zhurnal. 2013;(4, prilozhenie 1): 1–40. (In Russ.). Available at: http://www.scardio.ru/content/ Guidelines/beremennie_rek_2013.pdf.Кукес В.Г., Грачев С.В., Сычев Д.А., Раменская Г.В. Метаболизм лекарственных средств. Научные основы персонализированной медицины: руководство для врачей. М.: ГЭОТАР-Медиа, 2008. 304 с.Kukes V.G., Grachev S.V., Sychev D.A., Ramenskaya G.V. Metabolism of drugs. The scientific basis of personalized medicine: a guideline for physicians. Moskva: GEOTAR-Media, 2008. 304 p. (In Russ.).Bachmakov I., Werner U., Endress B. et al. Characterization of beta-adrenoceptor antagonists as substrates and inhibitors of the drug transporter P-glycoprotein. Fundam Clin Pharmacol. 2006;20(3):273–82.Bachmakov I., Werner U., Endress B. et al. Characterization of betaadrenoceptor antagonists as substrates and inhibitors of the drug transporter P-glycoprotein. Fundam Clin Pharmacol. 2006;20(3):273–82.Atkinson D.E., Brice-Bennett S., D’Souza S.W. Antiepileptic medication during pregnancy: does fetal genotypeaffect outcome? Pediatric Research. 2007;62(2):120–7.Atkinson D.E., Brice-Bennett S., D’Souza S.W. Antiepileptic medication during pregnancy: does fetal genotypeaffect outcome? Pediatric Research. 2007;62(2):120–7.Meador K.J., Baker G.A., Finnell R.H. et al. In utero antiepileptic drug exposure: fetal death and malformations. Neurology. 2006;67:407–12.Meador K.J., Baker G.A., Finnell R.H. et al. In utero antiepileptic drug exposure: fetal death and malformations. Neurology. 2006;67:407–12.Pennell P.B. Pregnancy in the woman with epilepsy: maternal and fetal outcomes. Semin Neurol. 2002;22:299–308.Pennell P.B. Pregnancy in the woman with epilepsy: maternal and fetal outcomes. Semin Neurol. 2002;22:299–308.Loscher W., Potschka H. Blood-brain barrier active efflux transporters: ATP-binding cassette gene family. NeuroRx. 2005;2(1):86–98.Loscher W., Potschka H. Blood-brain barrier active efflux transporters: ATP-binding cassette gene family. NeuroRx. 2005;2(1):86–98.Didziapetris R., Japertas P., Avdeef A., Petrauskas A. Classification analysis of P-glycoprotein substrate specificity. J Drug Target. 2003;11(7):391–406.Didziapetris R., Japertas P., Avdeef A., Petrauskas A. Classification analysis of P-glycoprotein substrate specificity. J Drug Target. 2003;11(7):391–406.Rahangdale L., Guerry S., Bauer H.M. et al. An observational cohort study of Chlamydia trachomatis treatment in pregnancy. Sex Transm Dis. 2006;33:106–10.Rahangdale L., Guerry S., Bauer H.M. et al. An observational cohort study of Chlamydia trachomatis treatment in pregnancy. Sex Transm Dis. 2006;33:106–10.Czeizel A.E., Rockenbauer M., Sorensen H.Y., Olsen J. A populationbased case-control teratologic study of oral erythromycin treatment during pregnancy. Reprod Toxicol. 1999;13:531–6.Czeizel A.E., Rockenbauer M., Sorensen H.Y., Olsen J. A populationbased case-control teratologic study of oral erythromycin treatment during pregnancy. Reprod Toxicol. 1999;13:531–6.Amsden G.W. Erythromycin, clarithromycin, and azithromycin: are the differences real? Clin Ther. 1996;18:56–72.Amsden G.W. Erythromycin, clarithromycin, and azithromycin: are the differences real? Clin Ther. 1996;18:56–72.Biaxin (Clarithromycin). Product Information. RxList. Internet Drug Index. Available at: http://www.rxlist.com/biaxin-drug.htm.Biaxin (Clarithromycin). Product Information. RxList. Internet Drug Index. Available at: http://www.rxlist.com/biaxin-drug.htm.Desmonts G., Couvreur J. Congenital toxoplasmosis: a prospective study of 378 pregnancies. New Engl J Med. 1974;50:1110–6.Desmonts G., Couvreur J. Congenital toxoplasmosis: a prospective study of 378 pregnancies. New Engl J Med. 1974;50:1110–6.Адамян Л.В., Афонина Л.Ю., Баранов И.И. и др. Применение антиретровирусных препаратов в комплексе мер, направленных на профилактику передачи ВИЧ от матери ребенку. Клинические рекомендации (протокол лечения). Проблемы репродукции. 2015;21(6S):215–45.Adamyan L.V., Afonina L.Yu., Baranov I.I. et al. The use of antiretroviral drugs in a set of measures aimed at preventing mother-to-child transmission of HIV. Clinical recommendations (treatment protocol). [Primenenie antiretrovirusnyh preparatov v komplekse mer, napravlennyh na profilaktiku peredachi VICh ot materi rebenku. Klinicheskie rekomendacii (protokol lecheniya)]. Problemy reprodukcii. 2015;21(6S):215–45. (In Russ.).Huisman M.T., Smit J.W., Schinkel A.H. Significance of P-glycoprotein for the pharmacology and clinical use of HIV protease inhibitors. AIDS. 2000;14(3):237–42.Huisman M.T., Smit J.W., Schinkel A.H. Significance of P-glycoprotein for the pharmacology and clinical use of HIV protease inhibitors. AIDS. 2000;14(3):237–42.Weiss J., Weis N., Ketabi-Kiyanvash N. et al. Comparison of the induction of P-glycoprotein activity by nucleotide,nucleoside, and non-nucleoside reverse transcriptase inhibitors. Eur J Pharmacol. 2008;579:104–9.Weiss J., Weis N., Ketabi-Kiyanvash N. et al. Comparison of the induction of P-glycoprotein activity by nucleotide,nucleoside, and non-nucleoside reverse transcriptase inhibitors. Eur J Pharmacol. 2008;579:104–9.Camus M., Delomenie C., Didier N. et al. Increased expression of MDR1 mRNAs and P-glycoprotein in placentas from HIV-1 infected women. Placenta. 2005;27:699–706.Camus M., Delomenie C., Didier N. et al. Increased expression of MDR1 mRNAs and P-glycoprotein in placentas from HIV-1 infected women. Placenta. 2005;27:699–706.Newell M.L. Mechanisms and timing of mother-to-child transmission of HIV-1. AIDS. 1998;12:831–7.Newell M.L. Mechanisms and timing of mother-to-child transmission of HIV-1. AIDS. 1998;12:831–7.Iqbal M., Audette M.C., Petropoulos S. et al. Placental drug transporters and their role in fetal protection. Placenta. 2012:33:137–42.Iqbal M., Audette M.C., Petropoulos S. et al. Placental drug transporters and their role in fetal protection. Placenta. 2012:33:137–42.

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