The 21 references with contexts in paper E. Sokova A., I. Mazerkina A., O. Demidova A., T. Aleksandrova V., Е. Сокова А., И. Мазеркина А., О. Демидова А., Т. Александрова В. (2018) “Особенности клинической фармакологии лекарственных средств, применяемых для фармакотерапии ВИЧ-инфекции во время беременности // Clinical pharmacology aspects of drugs for hiv-infected pregnant women” / spz:neicon:vedomostincesmp:y:2017:i:3:p:150-154

1
Darak S, Parchure R, Darak T, Talavlikar R, Kulkarni S, Kulkarni V. Advances in the prevention of mother-to-child transmission of HIV and resulting clinical and programmatic implications. Research and Reports in Neonatology 2014; 4: 111–23.
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    Íåñìîòðÿ íà ýòî, íà÷èíàÿ ñ 2003 ãîäà êîëè÷åñòâî äåòåé, çàáîëåâøèõ îò ÂÈ×-èíôèöèðîâàííûõ ìàòåðåé, óìåíüøèëîñü, ÷òî ñâÿçûâàþò ñ øèðîêèì ïðèìåíåíèåì õèìèîïðîôèëàêòèêè âåðòèêàëüíîé ïåðåäà÷è ÂÈ×-èíôåêöèè è âûïîëíåíèåì ýëåêòèâíîãî êåñàðåâà ñå÷åíèÿ
    Exact
    [1]
    Suffix
    . Ðåøåíèå î ïðîâåäåíèè àíòèðåòðîâèðóñíîé òåðàïèè (ÀÐÂÒ) ó ÂÈ×-èíôèöèðîâàííîé áåðåìåííîé æåíùèíû ÿâëÿåòñÿ êîìïëåêñíîé ïðîáëåìîé, ïîñêîëüêó îïðåäåëÿåòñÿ íå òîëüêî ñîâîêóïíîñòüþ ýïèäåìèîëîãè÷åñêèõ, êëèíè÷åñêèõ è ëàáîðàòîðíûõ ïîêàçàòåëåé, íî è ôèçèîëîãè÷åñêèìè îñîáåííîñòÿìè âî âðåìÿ áåðåìåííîñòè, êîòîðûå ïðåäîïðåäåëÿþò èçìåíåíèÿ ôàðìàêîêèíåòè÷åñêîãî ïðîôèëÿ, è, ñîîòâåòñòâåííî, ïîòåíöèàëüíóþ òîêñè÷

2
Roustit M, Jlaiel M, Leclercq P, Stanke-Labesque F. Pharmacokinetics and therapeutic drug monitoring of antiretrovirals in pregnant women. Br J Clin Pharmacol. 2008; 66(2): 179–95.
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  1. In-text reference with the coordinate start=3563
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    Âî âðåìÿ áåðåìåííîñòè îòìå÷àåòñÿ ðàçíîíàïðàâëåííîå èçìåíåíèå àêòèâíîñòè ìíîãèõ ïå÷åíî÷íûõ ôåðìåíòîâ, ó÷àñòâóþùèõâIèIIôàçàõ ìåòàáîëèçìà ëåêàðñòâåííûõ ñðåäñòâ (ËÑ), ÷òî ïðèâîäèò ê èçìåíåíèþ èõ ôàðìàêîêèíåòèêè, âêëþ÷àÿ è ÀÐÂÏ
    Exact
    [2–4]
    Suffix
    . Âîçðàñòàíèå ïî÷å÷íîãî êðîâîòîêà ó áåðåìåííîé ìîæåò ïðèâîäèòü ê óâåëè÷åíèþ êëèðåíñà ËÑ, êîòîðûå ýêñêðåòèðóþòñÿ ïî÷êàìè, íàïðèìåð íóêëåîçèäíûå/íóêëåîòèäíûå èíãèáèòîðû îáðàòíîé òðàíñêðèïòàçû (ÍÈÎÒ). Êðîìå òîãî, âàæíûì àñïåêòîì ïðèìåíåíèÿ ÀÐÂÏ ÿâëÿåòñÿ èõ âçàèìîäåéñòâèå ñ òðàíñïîðòåðàìè èç ñåìåéñòâà ABC è/èëè SLC, êîòîðîå èãðàåò âàæíóþ ðîëü â ìîäèôèêàöèè ôàðìàêîêèíåòè÷åñêèõ è ôàðìàêîäèíàìè÷åñêèõ ïðî

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    Êðîìå òîãî, âàæíûì àñïåêòîì ïðèìåíåíèÿ ÀÐÂÏ ÿâëÿåòñÿ èõ âçàèìîäåéñòâèå ñ òðàíñïîðòåðàìè èç ñåìåéñòâà ABC è/èëè SLC, êîòîðîå èãðàåò âàæíóþ ðîëü â ìîäèôèêàöèè ôàðìàêîêèíåòè÷åñêèõ è ôàðìàêîäèíàìè÷åñêèõ ïðîöåññîâ è, ñîîòâåòñòâåííî, èçìåíåíèè ýôôåêòèâíîñòè è áåçîïàñíîñòè âûñîêîàêòèâíîé àíòèðåòðîâèðóñíîé òåðàïèè (ÂÀÐÂÒ)
    Exact
    [2–4]
    Suffix
    . ÎÁÙÈÅ ÏÐÈÍÖÈÏÛ ÀÍÒÈÐÅÒÐÎÂÈÐÓÑÍÎÉ ÒÅÐÀÏÈÈ Àíòèðåòðîâèðóñíóþ òåðàïèþ ðåêîìåíäóþò âñåì ÂÈ×-èíôèöèðîâàííûì ïàöèåíòàì, âêëþ÷àÿ áåðåìåííûõ æåíùèí, íåçàâèñèìî îò èììóííîãî, êëèíè÷åñêîãî è âèðóñîëîãè÷åñêîãî ñòàòóñà [5].

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    Îíè õîðîøî ïðîíèêàþò ÷åðåç ïëàöåíòó ê ïëîäó, áûñòðî ïðîíèêàþò â ãðóäíîå ìîëîêî (èíäåêñ ìîëîêî/ïëàçìà ñîñòàâëÿåò 2,56 äëÿ ëàìèâóäèíà è 0,4 äëÿ çèäîâóäèíà). Áåðåìåííîñòü íå èçìåíÿåò â çíà÷èòåëüíîé ñòåïåíè ôàðìàêîêèíåòè÷åñêèå ïàðàìåòðû ýòèõ ïðåïàðàòîâ
    Exact
    [2, 4]
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    . Êëèíè÷åñêèå äàííûå ïî áåçîïàñíîñòè ïðèìåíåíèÿ ïðè áåðåìåííîñòè ïîëó÷åíû òîëüêî äëÿ çèäîâóäèíà, ëàìèâóäèíà, äèäàíîçèíà è ñòàâóäèíà.  èññëåäîâàíèè áîëåå 1000 äîêóìåíòèðîâàííûõ ñëó÷àåâ ïðèìåíåíèÿ çèäîâóäèíà ïðè áåðåìåííîñòè íå âûÿâëåíî çíà÷èòåëüíîãî òåðàòîãåííîãî äåéñòâèÿ.

4
Mattison DR. Clinical pharmacology during pregnancy. Amsterdam: Elsevier; 2013.
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  1. In-text reference with the coordinate start=7875
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    Îíè õîðîøî ïðîíèêàþò ÷åðåç ïëàöåíòó ê ïëîäó, áûñòðî ïðîíèêàþò â ãðóäíîå ìîëîêî (èíäåêñ ìîëîêî/ïëàçìà ñîñòàâëÿåò 2,56 äëÿ ëàìèâóäèíà è 0,4 äëÿ çèäîâóäèíà). Áåðåìåííîñòü íå èçìåíÿåò â çíà÷èòåëüíîé ñòåïåíè ôàðìàêîêèíåòè÷åñêèå ïàðàìåòðû ýòèõ ïðåïàðàòîâ
    Exact
    [2, 4]
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    . Êëèíè÷åñêèå äàííûå ïî áåçîïàñíîñòè ïðèìåíåíèÿ ïðè áåðåìåííîñòè ïîëó÷åíû òîëüêî äëÿ çèäîâóäèíà, ëàìèâóäèíà, äèäàíîçèíà è ñòàâóäèíà.  èññëåäîâàíèè áîëåå 1000 äîêóìåíòèðîâàííûõ ñëó÷àåâ ïðèìåíåíèÿ çèäîâóäèíà ïðè áåðåìåííîñòè íå âûÿâëåíî çíà÷èòåëüíîãî òåðàòîãåííîãî äåéñòâèÿ.

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     èññëåäîâàíèè áîëåå 1000 äîêóìåíòèðîâàííûõ ñëó÷àåâ ïðèìåíåíèÿ çèäîâóäèíà ïðè áåðåìåííîñòè íå âûÿâëåíî çíà÷èòåëüíîãî òåðàòîãåííîãî äåéñòâèÿ. Ïî äàííûì Ðåãèñòðà áåðåìåííîñòåé ïðè ïðèìåíåíèè ÀÐÂÒ (ÑØÀ), ÷àñòîòà ïîðîêîâ ðàçâèòèÿ äëÿ çèäîâóäèíà íå ïðåâûøàåò 2,8 %, äëÿ ëàìèâóäèíà — 3 %, äëÿ ñòàâóäèíà — 2,2 %
    Exact
    [4]
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    . Îñòàëüíûå ÍÈÎÒ ñ÷èòàþòñÿ àëüòåðíàòèâíûìè ïðåïàðàòàìè âî âðåìÿ áåðåìåííîñòè ó ÂÈ×-èíôèöèðîâàííûõ æåíùèí. Âîçäåéñòâèå íà îðãàíèçì ìàòåðè ýìòðèöèòàáèíà è òåíîôîâèðà (êàòåãîðèÿ Â) ñíèæàåòñÿ â III òðèìåñòðå ïî ñðàâíåíèþ ñ ïîñëåðîäîâûì ïåðèîäîì, îäíàêî êîíöåíòðàöèè ïðåïàðàòîâ îñòàþòñÿ íà óðîâíå òåðàïåâòè÷åñêèõ è êîððåêöèè ðåæèìà äîçèðîâàíèÿ â III òðèìåñòðå íå òðåáóåòñÿ [11].

5
Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents. Department of Health and Human Services [Internet]. 2016 [cited 2017 Jul 10]. Available from: https://goo.gl/ RpJPfc.
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  1. In-text reference with the coordinate start=4295
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    ÎÁÙÈÅ ÏÐÈÍÖÈÏÛ ÀÍÒÈÐÅÒÐÎÂÈÐÓÑÍÎÉ ÒÅÐÀÏÈÈ Àíòèðåòðîâèðóñíóþ òåðàïèþ ðåêîìåíäóþò âñåì ÂÈ×-èíôèöèðîâàííûì ïàöèåíòàì, âêëþ÷àÿ áåðåìåííûõ æåíùèí, íåçàâèñèìî îò èììóííîãî, êëèíè÷åñêîãî è âèðóñîëîãè÷åñêîãî ñòàòóñà
    Exact
    [5]
    Suffix
    . ÀÐÂÒ ñíèæàåò çàáîëåâàåìîñòü è ñìåðòíîñòü è ó ïàöèåíòîâ ñ âûñîêèì êîëè÷åñòâîì CD4-ëèìôîöèòîâ [6]. Öåëü àíòèðåòðîâèðóñíîé òåðàïèè ïðè áåðåìåííîñòè ñîñòîèò â òîì, ÷òîáû, ñ îäíîé ñòîðîíû, ïðåäîòâðàòèòü ïåðåäà÷ó ÂÈ× îò ìàòåðè ðåáåíêó, à ñ äðóãîé – îáåñïå÷èòü îïòèìàëüíîå ëå÷åíèå áåðåìåííîé, êîòîðîå ñîïðîâîæäàëîñü áû ïî âîçìîæíîñòè ìèíèìàëüíûì íåæåëàòåëüíûì äåéñòâèåì ïðåïàðàòà íà îðãàíèçì ìàòåðè è åùå

6
Lundgren JD, Babiker AG, Gordin F, Emery S, Grund B, Sharma S, et al. Initiation of antiretroviral therapy in early asymptomatic HIV Infection. ¹ Engl J Med. 2015; 373(9): 795–807.
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    ÎÁÙÈÅ ÏÐÈÍÖÈÏÛ ÀÍÒÈÐÅÒÐÎÂÈÐÓÑÍÎÉ ÒÅÐÀÏÈÈ Àíòèðåòðîâèðóñíóþ òåðàïèþ ðåêîìåíäóþò âñåì ÂÈ×-èíôèöèðîâàííûì ïàöèåíòàì, âêëþ÷àÿ áåðåìåííûõ æåíùèí, íåçàâèñèìî îò èììóííîãî, êëèíè÷åñêîãî è âèðóñîëîãè÷åñêîãî ñòàòóñà [5]. ÀÐÂÒ ñíèæàåò çàáîëåâàåìîñòü è ñìåðòíîñòü è ó ïàöèåíòîâ ñ âûñîêèì êîëè÷åñòâîì CD4-ëèìôîöèòîâ
    Exact
    [6]
    Suffix
    . Öåëü àíòèðåòðîâèðóñíîé òåðàïèè ïðè áåðåìåííîñòè ñîñòîèò â òîì, ÷òîáû, ñ îäíîé ñòîðîíû, ïðåäîòâðàòèòü ïåðåäà÷ó ÂÈ× îò ìàòåðè ðåáåíêó, à ñ äðóãîé – îáåñïå÷èòü îïòèìàëüíîå ëå÷åíèå áåðåìåííîé, êîòîðîå ñîïðîâîæäàëîñü áû ïî âîçìîæíîñòè ìèíèìàëüíûì íåæåëàòåëüíûì äåéñòâèåì ïðåïàðàòà íà îðãàíèçì ìàòåðè è åùå íå ðîäèâøåãîñÿ ðåáåíêà [7, 8].

7
Recommendations for use of antiretroviral drugs in pregnant HIV-1-infected women for maternal health and interventions to reduce perinatal HIV transmission in the United States [Internet]. 2016 [cited 2017 Jul 10]. Available from: https:// goo.gl/5VKzKy.
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    Öåëü àíòèðåòðîâèðóñíîé òåðàïèè ïðè áåðåìåííîñòè ñîñòîèò â òîì, ÷òîáû, ñ îäíîé ñòîðîíû, ïðåäîòâðàòèòü ïåðåäà÷ó ÂÈ× îò ìàòåðè ðåáåíêó, à ñ äðóãîé – îáåñïå÷èòü îïòèìàëüíîå ëå÷åíèå áåðåìåííîé, êîòîðîå ñîïðîâîæäàëîñü áû ïî âîçìîæíîñòè ìèíèìàëüíûì íåæåëàòåëüíûì äåéñòâèåì ïðåïàðàòà íà îðãàíèçì ìàòåðè è åùå íå ðîäèâøåãîñÿ ðåáåíêà
    Exact
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    . Ó áåðåìåííûõ æåíùèí âûáîð ðåæèìà ÀÐÂÒ äîëæåí ïðåäóñìàòðèâàòü íàëè÷èå ðåçèñòåíòíîñòè âèðóñíîãî ïðîôèëÿ, áåçîïàñíîñòü è ýôôåêòèâíîñòü ïðåïàðàòîâ äëÿ ìàòåðè è ïëîäà, ïîòåíöèàëüíóþ âîçìîæíîñòü âçàèìîäåéñòâèÿ ñ äðóãèìè ËÑ è ôàðìàêîêèíåòè÷åñêèå äàííûå ïðè áåðåìåííîñòè.

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    Ñîâðåìåííîå ñîñòîÿíèå âîïðîñà ïî ïðîôèëàêòèêå, ëå÷åíèþ ÂÈ×-èíôåêöèè âî âðåìÿ áåðåìåííîñòè è ïðîâåäåíèþ ìåðîïðèÿòèé ïî ñîêðàùåíèþ ïåðèíàòàëüíîãî ÂÈ×-èíôèöèðîâàíèÿ â ÑØÀ ïðåäñòàâëåíî â ñîîòâåòñòâóþùèõ ðåêîìåíäàöèÿõ
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    . Ïðîôèëàêòèêà ïåðåäà÷è ÂÈ×-èíôåêöèè îò ìàòåðè ðåáåíêó (ÏÏÌÐ) – êîìïëåêñíàÿ çàäà÷à, óñïåõ ðåøåíèÿ êîòîðîé ñêëàäûâàåòñÿ èç âûïîëíåíèÿ ñëåäóþùèõ ýòàïîâ: ïåðâè÷íàÿ ïðîôèëàêòèêà ÂÈ×-èíôåêöèè ó æåíùèí ðåïðîäóêòèâíîãî âîçðàñòà; ðàííåå âûÿâëåíèå ÂÈ×-èíôåêöèè ó æåíùèí ðåïðîäóêòèâíîãî âîçðàñòà; íàçíà÷åíèå ÀÐÂÒ ÂÈ×-èíôèöèðîâàííûì æåíùèíàì, ïëàíèðóþùèì áåðåìåííîñòü; íàçíà÷åíèå ÀÐÂÒ âñåì ÂÈ×-èíôèöèðîâàííûì

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    Ýòî ïîâûøàåò âåðîÿòíîñòü òîêñè÷åñêîãî äåéñòâèÿ ïðåïàðàòîâ è âûçûâàåò íåîáõîäèìîñòü ïðîâåäåíèÿ òåðàïåâòè÷åñêîãî ëåêàðñòâåííîãî ìîíèòîðèíãà äëÿ ïîäáîðà èíäèâèäóàëüíûõ äîç èíãèáèòîðîâ ïðîòåàç íà ïðîòÿæåíèè âñåãî ãåñòàöèîííîãî ïåðèîäà áåðåìåííîñòè. Ñàêâèíàâèð â êîìáèíàöèè ñ ðèòîíàâèðîì ÿâëÿåòñÿ åùå îäíîé àëüòåðíàòèâîé äëÿ ïðèìåíåíèÿ âî âðåìÿ áåðåìåííîñòè
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    . Ó ñàêâèíàâèðà îòìå÷àåòñÿ âûñîêàÿ ñâÿçü ñ áåëêàìè (98 %), ïðåïàðàò ÿâëÿåòñÿ îäíîâðåìåííî ñóáñòðàòîì è èíãèáèòîðîì CYP3A4 è ãëèêîïðîòåèíà Ð,Ò1/2ñîñòàâëÿåò 12 ÷. Ðåçóëüòàòû ïðîâîäèâøèõñÿ èññëåäîâàíèé íå âûÿâèëè çíà÷èìûõ ðàçëè÷èé â ôàðìàêîêèíåòè÷åñêèõ ïàðàìåòðàõ êîìáèíàöèè ñàêâèíàâèð/ðèòîíàâèð ìåæäó II, III òðèìåñòðîì áåðåìåííîñòè è ïîñëåðîäîâûì ïåðèîäîì, ïîýòîìó íåò íåîáõîäèìîñòè èçìåíåíèé ðåêîìåíä

8
Zhuravleva EO, Velts NYu, Zatolochina KE, Glagolev SV, Polivanov VA, Darmostukova MA, et al. Analysis of spontaneous reports of adverse reactions, developed in the use of drugs during pregnancy.Safety and Risk of Pharmacotherapy 2017; 5(2): 61–69 (in Russian).
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    Öåëü àíòèðåòðîâèðóñíîé òåðàïèè ïðè áåðåìåííîñòè ñîñòîèò â òîì, ÷òîáû, ñ îäíîé ñòîðîíû, ïðåäîòâðàòèòü ïåðåäà÷ó ÂÈ× îò ìàòåðè ðåáåíêó, à ñ äðóãîé – îáåñïå÷èòü îïòèìàëüíîå ëå÷åíèå áåðåìåííîé, êîòîðîå ñîïðîâîæäàëîñü áû ïî âîçìîæíîñòè ìèíèìàëüíûì íåæåëàòåëüíûì äåéñòâèåì ïðåïàðàòà íà îðãàíèçì ìàòåðè è åùå íå ðîäèâøåãîñÿ ðåáåíêà
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    [7, 8]
    Suffix
    . Ó áåðåìåííûõ æåíùèí âûáîð ðåæèìà ÀÐÂÒ äîëæåí ïðåäóñìàòðèâàòü íàëè÷èå ðåçèñòåíòíîñòè âèðóñíîãî ïðîôèëÿ, áåçîïàñíîñòü è ýôôåêòèâíîñòü ïðåïàðàòîâ äëÿ ìàòåðè è ïëîäà, ïîòåíöèàëüíóþ âîçìîæíîñòü âçàèìîäåéñòâèÿ ñ äðóãèìè ËÑ è ôàðìàêîêèíåòè÷åñêèå äàííûå ïðè áåðåìåííîñòè.

9
The use of antiretroviral drugs as part of a set of measures aimed at preventing the transmission of HIV from mother to child. Clinical recommendations (protocol of treatment) of the Ministry of Health of the Russian Federation. Available from: http://minzdrav.midural.ru/uploads/1120%D0%B0.pdf (in Russian).
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    ÀÐÂÏ, êîòîðûå ðåêîìåíäóþòñÿ äëÿ íàçíà÷åíèÿ â îáùåé ïîïóëÿöèè, â ðÿäå ñëó÷àåâ íå íàçíà÷àþòñÿ áåðåìåííûì æåíùèíàì â ñâÿçè ñ îãðàíè÷åííîñòüþ îïûòà èõ ïðèìåíåíèÿ, òî åñòü ñëåäóåò íàçíà÷àòü òîëüêî òå ÀÐÂÏ, êîòîðûå èñïûòàíû ìíîãîëåòíåé ïðàêòèêîé. Êîìáèíèðîâàííàÿ òåðàïèÿ ÀÐÂÏ â òå÷åíèå âñåé áåðåìåííîñòè ÿâëÿåòñÿ ñòàíäàðòîì ëå÷åíèÿ, êîòîðûé îòðàæåí â êëèíè÷åñêèõ ðåêîìåíäàöèÿõ Ìèíçäðàâà Ðîññèè
    Exact
    [9]
    Suffix
    . Ñîâðåìåííîå ñîñòîÿíèå âîïðîñà ïî ïðîôèëàêòèêå, ëå÷åíèþ ÂÈ×-èíôåêöèè âî âðåìÿ áåðåìåííîñòè è ïðîâåäåíèþ ìåðîïðèÿòèé ïî ñîêðàùåíèþ ïåðèíàòàëüíîãî ÂÈ×-èíôèöèðîâàíèÿ â ÑØÀ ïðåäñòàâëåíî â ñîîòâåòñòâóþùèõ ðåêîìåíäàöèÿõ [7].

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    Prefix
    çàäà÷à, óñïåõ ðåøåíèÿ êîòîðîé ñêëàäûâàåòñÿ èç âûïîëíåíèÿ ñëåäóþùèõ ýòàïîâ: ïåðâè÷íàÿ ïðîôèëàêòèêà ÂÈ×-èíôåêöèè ó æåíùèí ðåïðîäóêòèâíîãî âîçðàñòà; ðàííåå âûÿâëåíèå ÂÈ×-èíôåêöèè ó æåíùèí ðåïðîäóêòèâíîãî âîçðàñòà; íàçíà÷åíèå ÀÐÂÒ ÂÈ×-èíôèöèðîâàííûì æåíùèíàì, ïëàíèðóþùèì áåðåìåííîñòü; íàçíà÷åíèå ÀÐÂÒ âñåì ÂÈ×-èíôèöèðîâàííûì áåðåìåííûì; íàçíà÷åíèå ÀÐÂÒ â ðîäàõ; íàçíà÷åíèå ÀÐÂÒ ðåáåíêó
    Exact
    [9]
    Suffix
    . Ñóùåñòâóþò 4 ãðóïïû àíòèðåòðîâèðóñíûõ ïðåïàðàòîâ [10]: 1) íóêëåîçèäíûå/íóêëåîòèäíûå èíãèáèòîðû îáðàòíîé òðàíñêðèïòàçû (ÍÈÎÒ). Ê íèì îòíîñÿòñÿ: çèäîâóäèí (Retrovir®), ëàìèâóäèí (Epivir®), àáàêàâèð (Ziagen®), äèäàíîçèí/ddI (Videx®), ñòàâóäèí/d4T (Zerit®), ýìòðèöèòàáèí (Emtriva®), çàëüöèòàáèí (HIVID®) è òåíîôîâèð (Viread®).

10
Schaefer C, Spielmann H, Vetter K. Drug therapy during pregnancy and lactation. Moscow: Logosfera; 2010 (in Russian).
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    âûïîëíåíèÿ ñëåäóþùèõ ýòàïîâ: ïåðâè÷íàÿ ïðîôèëàêòèêà ÂÈ×-èíôåêöèè ó æåíùèí ðåïðîäóêòèâíîãî âîçðàñòà; ðàííåå âûÿâëåíèå ÂÈ×-èíôåêöèè ó æåíùèí ðåïðîäóêòèâíîãî âîçðàñòà; íàçíà÷åíèå ÀÐÂÒ ÂÈ×-èíôèöèðîâàííûì æåíùèíàì, ïëàíèðóþùèì áåðåìåííîñòü; íàçíà÷åíèå ÀÐÂÒ âñåì ÂÈ×-èíôèöèðîâàííûì áåðåìåííûì; íàçíà÷åíèå ÀÐÂÒ â ðîäàõ; íàçíà÷åíèå ÀÐÂÒ ðåáåíêó [9]. Ñóùåñòâóþò 4 ãðóïïû àíòèðåòðîâèðóñíûõ ïðåïàðàòîâ
    Exact
    [10]
    Suffix
    : 1) íóêëåîçèäíûå/íóêëåîòèäíûå èíãèáèòîðû îáðàòíîé òðàíñêðèïòàçû (ÍÈÎÒ). Ê íèì îòíîñÿòñÿ: çèäîâóäèí (Retrovir®), ëàìèâóäèí (Epivir®), àáàêàâèð (Ziagen®), äèäàíîçèí/ddI (Videx®), ñòàâóäèí/d4T (Zerit®), ýìòðèöèòàáèí (Emtriva®), çàëüöèòàáèí (HIVID®) è òåíîôîâèð (Viread®).

11
Best B, Stek A, Hu C, Burchett SK, Rossi SS, Smith E, et al. High-dose Lopinavir and standard dose emtricitabine pharmacokinetics during pregnancy and postpartum. 15th Conference on Retroviruses and Opportunistic Infections, February 3–6, 2008, Boston, MA, USA.
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    Âîçäåéñòâèå íà îðãàíèçì ìàòåðè ýìòðèöèòàáèíà è òåíîôîâèðà (êàòåãîðèÿ Â) ñíèæàåòñÿ â III òðèìåñòðå ïî ñðàâíåíèþ ñ ïîñëåðîäîâûì ïåðèîäîì, îäíàêî êîíöåíòðàöèè ïðåïàðàòîâ îñòàþòñÿ íà óðîâíå òåðàïåâòè÷åñêèõ è êîððåêöèè ðåæèìà äîçèðîâàíèÿ â III òðèìåñòðå íå òðåáóåòñÿ
    Exact
    [11]
    Suffix
    . Èç ïðåäñòàâèòåëåé ïåðâîãî ïîêîëåíèÿ ÍÍÈÎÒ äåëàâèðäèí â íàñòîÿùåå âðåìÿ íå ïðèìåíÿåòñÿ. Êëèíè÷åñêèå äàííûå î ïðèìåíåíèè âî âðåìÿ áåðåìåííîñòè ïîëó÷åíû òîëüêî äëÿ ýôàâèðåíçà è íåâèðàïèíà. Ó ýôàâèðåíçà (êàòåãîðèÿ D) îòìå÷àåòñÿ âûñîêàÿ ñâÿçü ñ áåëêàìè (>99 %), ïðåïàðàò ìåòàáîëèçèðóåòñÿ CYP3A4 è 2B6, èíäóöèðóåò èçîôåðìåíò CYP3A4,Ò1/2 ñîñòàâëÿåò 40–55 ÷.

12
Capparelli EV, Aweeka F, Hitti J, Stek A, Hu C, Burchett SK, et al. Chronic administration of Nevirapine during pregnancy: impact of pregnancy on pharmacokinetics. HIV Med. 2008; 9(4): 214–20.
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    Íåâèðàïèí õîðîøî ïðîíèêàåò ÷åðåç ïëàöåíòó, à êîíöåíòðàöèÿ â ãðóäíîì ìîëîêå ñîñòàâëÿåò 76 % îò êîíöåíòðàöèè ïðåïàðàòà â ïëàçìå êðîâè ìàòåðè. Èññëåäîâàíèÿ, ïðîâåäåííûå â ÑØÀ, íå ïðîäåìîíñòðèðîâàëè èçìåíåíèé ôàðìàêîêèíåòèêè âî âðåìÿ áåðåìåííîñòè, ïîýòîìó åãî ðåêîìåíäóþò ïðèìåíÿòü â ñòàíäàðòíûõ äîçàõ
    Exact
    [12]
    Suffix
    . Èíôîðìàöèÿ ïî ïðèìåíåíèþ ïðåïàðàòîâ ÍÍÈÎÒ âòîðîãî ïîêîëåíèÿ â êà÷åñòâå ÀÐÂÒ îãðàíè÷åíà â ñâÿçè ñ îòñóòñòâèåì äàííûõ ïî ôàðìàêîêèíåòèêå, ñòåïåíè ïðîõîæäåíèÿ ÷åðåç ïëàöåíòó è ïðîíèêíîâåíèþ â ãðóäíîå ìîëîêî.

13
Lugt J, Colbers A, Molto J, Hawkins D, van der Ende M, Vogel M, et al. The pharmacokinetics, safety and efficacy of boosted Saquinavir tablets in HIV type-1-infected pregnant women. Antivir Ther. 2009; 14(3): 443–50.
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    Ðåçóëüòàòû ïðîâîäèâøèõñÿ èññëåäîâàíèé íå âûÿâèëè çíà÷èìûõ ðàçëè÷èé â ôàðìàêîêèíåòè÷åñêèõ ïàðàìåòðàõ êîìáèíàöèè ñàêâèíàâèð/ðèòîíàâèð ìåæäó II, III òðèìåñòðîì áåðåìåííîñòè è ïîñëåðîäîâûì ïåðèîäîì, ïîýòîìó íåò íåîáõîäèìîñòè èçìåíåíèé ðåêîìåíäóåìîãî ðåæèìà äîçèðîâàíèÿ ñàêâèíàâèð 1000 ìã/ðèòîíàâèð 100 ìã äâà ðàçà/ñóòêè
    Exact
    [13]
    Suffix
    .  ñëó÷àå ðàçâèòèÿ òîëåðàíòíîñòè ê îñíîâíûì ïðåïàðàòàì èç ãðóïïû èíãèáèòîðîâ ïðîòåàç äëÿ õèìèîïðîôèëàêòèêè âåðòèêàëüíîé ïåðåäà÷è ÂÈ×-èíôåêöèè ïðèìåíÿþò íåëôèíàâèð. Ñîâðåìåííûé ïîäõîä ê ïðîôèëàêòèêå âåðòèêàëüíîé ïåðåäà÷è ÂÈ×-èíôåêöèè îò ìàòåðè ðåáåíêó ïðåäïîëàãàåò ïðèìåíåíèå âûñîêîàêòèâíîé àíòèðåòðîâèðóñíîé òåðàïèè — ÂÀÐÂÒ, êîòîðàÿ ïðåäóñìàòðèâàåò êîìáèíàöèþ ÍÈÎÒ âìåñòå ñ ÍÍÈÎÒ èëè èíãèáèòîðàìè ïð

14
Cock KM, Fowler MG, Mercier E, de Vincenzi I, Saba J, Hoff E, et al. Prevention of mother-to-child HIV transmission in resource-poor countries: translating research into policy and practice. JAMA 2000; 283(9): 1175–82.
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    Ñîâðåìåííûé ïîäõîä ê ïðîôèëàêòèêå âåðòèêàëüíîé ïåðåäà÷è ÂÈ×-èíôåêöèè îò ìàòåðè ðåáåíêó ïðåäïîëàãàåò ïðèìåíåíèå âûñîêîàêòèâíîé àíòèðåòðîâèðóñíîé òåðàïèè — ÂÀÐÂÒ, êîòîðàÿ ïðåäóñìàòðèâàåò êîìáèíàöèþ ÍÈÎÒ âìåñòå ñ ÍÍÈÎÒ èëè èíãèáèòîðàìè ïðîòåàç è âëèÿåò íà ðàçëè÷íûå ñòàäèè ðåïëèêàöèè ÂÈ×. Áûëî ïîêàçàíî, ÷òî ïðèìåíåíèå ÂÀÐÂÒ ïîçâîëÿåò ñíèçèòü âåðîÿòíîñòü èíôèöèðîâàíèÿ ðåáåíêà ñ 20–45 % äî 1 %
    Exact
    [14]
    Suffix
    .  ðÿäå èññëåäîâàíèé áûëî ïðîäåìîíñòðèðîâàíî, ÷òî áîëüøèíñòâî ïðåïàðàòîâ ÍÈÎÒ/ÍÍÈÎÒ âçàèìîäåéñòâóþò ñ ÀÂÑ-òðàíñïîðòåðàìè, îäíàêî õîðîøî ïðîíèêàþò ÷åðåç ïëàöåíòàðíûé áàðüåð, è êîíöåíòðàöèè ïðåïàðàòîâ ïðàêòè÷åñêè îäèíàêîâû â ïóïîâèíå ðåáåíêà è â êðîâè ìàòåðè [15, 16].

15
Flynn PM, Mirochnick M, Shapiro DE, Bardeguez A, Rodman J, Robbins B, et al. Pharmacokinetics and safety of single-dose Tenofovir disoproxil fumarate and Emtricitabine in HIV-1-infected pregnant women and their infants. Antimicrob Agents Chemother. 2011; 55(12): 5914–22.
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     ðÿäå èññëåäîâàíèé áûëî ïðîäåìîíñòðèðîâàíî, ÷òî áîëüøèíñòâî ïðåïàðàòîâ ÍÈÎÒ/ÍÍÈÎÒ âçàèìîäåéñòâóþò ñ ÀÂÑ-òðàíñïîðòåðàìè, îäíàêî õîðîøî ïðîíèêàþò ÷åðåç ïëàöåíòàðíûé áàðüåð, è êîíöåíòðàöèè ïðåïàðàòîâ ïðàêòè÷åñêè îäèíàêîâû â ïóïîâèíå ðåáåíêà è â êðîâè ìàòåðè
    Exact
    [15, 16]
    Suffix
    . Íàïðîòèâ, òðàíñïëàöåíòàðíîå ïðîõîæäåíèå èíãèáèòîðîâ ïðîòåàç î÷åíü îãðàíè÷åíî è ñîñòàâëÿåò ïðèìåðíî 0–0,2 äëÿ ðèòîíàâèðà, 0–0,1 äëÿ ëîïèíàâèðà è ìåíåå 0,3 äëÿ íåëôèíàâèðà, ñàêâèíàâèðà è èíäèíàâèðà [17].

16
Sokova EA. Monitoring post-approval drug safety in pregnancy: pharmacogenetic aspects. Safety and Risk of Pharmacotherapy 2015; (3): 30–35 (in Russian).
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     ðÿäå èññëåäîâàíèé áûëî ïðîäåìîíñòðèðîâàíî, ÷òî áîëüøèíñòâî ïðåïàðàòîâ ÍÈÎÒ/ÍÍÈÎÒ âçàèìîäåéñòâóþò ñ ÀÂÑ-òðàíñïîðòåðàìè, îäíàêî õîðîøî ïðîíèêàþò ÷åðåç ïëàöåíòàðíûé áàðüåð, è êîíöåíòðàöèè ïðåïàðàòîâ ïðàêòè÷åñêè îäèíàêîâû â ïóïîâèíå ðåáåíêà è â êðîâè ìàòåðè
    Exact
    [15, 16]
    Suffix
    . Íàïðîòèâ, òðàíñïëàöåíòàðíîå ïðîõîæäåíèå èíãèáèòîðîâ ïðîòåàç î÷åíü îãðàíè÷åíî è ñîñòàâëÿåò ïðèìåðíî 0–0,2 äëÿ ðèòîíàâèðà, 0–0,1 äëÿ ëîïèíàâèðà è ìåíåå 0,3 äëÿ íåëôèíàâèðà, ñàêâèíàâèðà è èíäèíàâèðà [17].

17
Gedeon C, Koren G. Designing pregnancy centered medications: drugs which do not cross the human placenta. Placenta 2006; 27(8): 861–8.
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    Íàïðîòèâ, òðàíñïëàöåíòàðíîå ïðîõîæäåíèå èíãèáèòîðîâ ïðîòåàç î÷åíü îãðàíè÷åíî è ñîñòàâëÿåò ïðèìåðíî 0–0,2 äëÿ ðèòîíàâèðà, 0–0,1 äëÿ ëîïèíàâèðà è ìåíåå 0,3 äëÿ íåëôèíàâèðà, ñàêâèíàâèðà è èíäèíàâèðà
    Exact
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    . Ýòîò ôàêò ìîæíî îáúÿñíèòü òåì, ÷òî ÈÏ ÿâëÿþòñÿ ñóáñòðàòàìè òðàíñïîðòåðîâ èç ñåìåéñòâà ABC è/èëè SLC [18]. Íåêîòîðûå ÀÐÂÏ îáëàäàþò ñïîñîáíîñòüþ èíãèáèðîâàòü òðàíñïîðòåðû èç ñåìåéñòâà ABC è/èëè SLC (íàïðèìåð, ýôàâèðåíç, íåâèðàïèí, àáàêàâèð èíãèáèðóþò ãëèêîïðîòåèí Ð) [19].

18
Sudhakaran S, Rayner CR, Li J, Kong DC, Gude NM, Nation RL. Inhibition of placental P-glycoprotein: impact on indinavir transfer to the foetus. Br J Clin Pharmacol. 2008; 65(5): 667–73.
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    Íàïðîòèâ, òðàíñïëàöåíòàðíîå ïðîõîæäåíèå èíãèáèòîðîâ ïðîòåàç î÷åíü îãðàíè÷åíî è ñîñòàâëÿåò ïðèìåðíî 0–0,2 äëÿ ðèòîíàâèðà, 0–0,1 äëÿ ëîïèíàâèðà è ìåíåå 0,3 äëÿ íåëôèíàâèðà, ñàêâèíàâèðà è èíäèíàâèðà [17]. Ýòîò ôàêò ìîæíî îáúÿñíèòü òåì, ÷òî ÈÏ ÿâëÿþòñÿ ñóáñòðàòàìè òðàíñïîðòåðîâ èç ñåìåéñòâà ABC è/èëè SLC
    Exact
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    . Íåêîòîðûå ÀÐÂÏ îáëàäàþò ñïîñîáíîñòüþ èíãèáèðîâàòü òðàíñïîðòåðû èç ñåìåéñòâà ABC è/èëè SLC (íàïðèìåð, ýôàâèðåíç, íåâèðàïèí, àáàêàâèð èíãèáèðóþò ãëèêîïðîòåèí Ð) [19]. Áûëî ïðîäåìîíñòðèðîâàíî, ÷òî àáàêàâèð, çèäîâóäèí, òåíîôîâèð àêòèâíî èíãèáèðóþò òðàíñïîðòåðû èç ñåìåéñòâà îðãàíè÷åñêèõ êàòèîíî⠗ OCT1, OCT2 è OCT3, êîòîðûå èãðàþò âàæíóþ ðîëü âî âñàñûâàíèè, ðàñïðåäåëåíèè è àêòèâíîé ñåêðåöèè ãèäðîôèëü

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    Ïðåäïîëàãàþò, ÷òî ðèòîíàâèð ìîæåò èíãèáèðîâàòü àêòèâíîñòü ïëàöåíòàðíûõ òðàíñïîðòåðî⠗ ãëèêîïðîòåèíà Ð è ïðîòåèíà ðåçèñòåíòíîñòè ðàêà ãðóäè, è, òàêèì îáðàçîì, óâåëè÷èâàåòñÿ ñòåïåíü âîçäåéñòâèÿ íà ïëîä äðóãèõ êîìïîíåíòîâ ÂÀÐÂÒ
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    [18]
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    . ÇÀÊËÞ×ÅÍÈÅ Èçìåíåíèÿ ôàðìàêîêèíåòè÷åñêîãî ïðîôèëÿ ÀÐÂÏ âî âðåìÿ áåðåìåííîñòè ïðåäîïðåäåëÿåò ïîòåíöèàëüíóþ òîêñè÷íîñòü àíòèðåòðîâèðóñíûõ ïðåïàðàòîâ äëÿ ìàòåðè è ïëîäà/íîâîðîæäåííîãî. Ýòî ïðåäïîëàãàåò íåîáõîäèìîñòü ïðîâåäåíèÿ òåðàïåâòè÷åñêîãî ëåêàðñòâåííîãî ìîíèòîðèíãà ÀÐÂÏ ó ÂÈ×-èíôèöèðîâàííûõ áåðåìåííûõ æåíùèí äëÿ ïîäáîðà èíäèâèäóàëüíûõ äîç èíãèáèòîðîâ ïðîòåàç íà ïðîòÿæåíèè âñåãî

19
Storch CH, Theile D, Lindenmaier H, Haefeli WE, Weiss J. Comparison of the inhibitory activity of anti-HIV drugs on P-glycoprotein. Biochem Pharmacol. 2007; 73(10): 1573–81.
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    Ýòîò ôàêò ìîæíî îáúÿñíèòü òåì, ÷òî ÈÏ ÿâëÿþòñÿ ñóáñòðàòàìè òðàíñïîðòåðîâ èç ñåìåéñòâà ABC è/èëè SLC [18]. Íåêîòîðûå ÀÐÂÏ îáëàäàþò ñïîñîáíîñòüþ èíãèáèðîâàòü òðàíñïîðòåðû èç ñåìåéñòâà ABC è/èëè SLC (íàïðèìåð, ýôàâèðåíç, íåâèðàïèí, àáàêàâèð èíãèáèðóþò ãëèêîïðîòåèí Ð)
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    . Áûëî ïðîäåìîíñòðèðîâàíî, ÷òî àáàêàâèð, çèäîâóäèí, òåíîôîâèð àêòèâíî èíãèáèðóþò òðàíñïîðòåðû èç ñåìåéñòâà îðãàíè÷åñêèõ êàòèîíî⠗ OCT1, OCT2 è OCT3, êîòîðûå èãðàþò âàæíóþ ðîëü âî âñàñûâàíèè, ðàñïðåäåëåíèè è àêòèâíîé ñåêðåöèè ãèäðîôèëüíûõ ËÑ â ìî÷ó [20].

20
Minuesa G, Volk C, Molina-Arcas M, Gorboulev V, Erkizia I, Arndt P, et al. Transport of lamivudine [(-)-beta-L-2¢,3¢-dideoxy-3¢-thiacytidine] and high-affinity interaction of nucleoside reverse transcriptase inhibitors with human organic cation transporters 1, 2, and 3. J Pharmacol Exp Ther. 2009; 329(1): 252–61.
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    Áûëî ïðîäåìîíñòðèðîâàíî, ÷òî àáàêàâèð, çèäîâóäèí, òåíîôîâèð àêòèâíî èíãèáèðóþò òðàíñïîðòåðû èç ñåìåéñòâà îðãàíè÷åñêèõ êàòèîíî⠗ OCT1, OCT2 è OCT3, êîòîðûå èãðàþò âàæíóþ ðîëü âî âñàñûâàíèè, ðàñïðåäåëåíèè è àêòèâíîé ñåêðåöèè ãèäðîôèëüíûõ ËÑ â ìî÷ó
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    . Ëîïèíàâèð, íåëôèíàâèð, ñàêâèíàâèð ñíèæàþò ñåêðåòîðíóþ àêòèâíîñòü ïðîòåèíà ðåçèñòåíòíîñòè ðàêà ãðóäè (BCRP) òðàíñïîðòåðà [21]. Òàêèì îáðàçîì, âçàèìîäåéñòâèå ÀÐÂÏ ñ ðàçëè÷íûìè òðàíñïîðòåðàìè ËÑ èãðàåò âàæíóþ ðîëü â ìîäèôèêàöèè ôàðìàêîêèíåòè÷åñêèõ è ôàðìàêîäèíàìè÷åñêèõ ïðîöåññîâ è, ñîîòâåòñòâåííî, ýôôåêòèâíîñòè è áåçîïàñíîñòè ÂÀÐÂÒ [22].

21
Weiss J, Rose J, Storch CH, Ketabi-Kiyanvash N, Sauer A, Haefeli WE, Efferth T. Modulation of human BCRP (ABCG2) activity by anti-HIV drugs. J Antimicrob Chemother. 2007; 59(2): 238–45.
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    Áûëî ïðîäåìîíñòðèðîâàíî, ÷òî àáàêàâèð, çèäîâóäèí, òåíîôîâèð àêòèâíî èíãèáèðóþò òðàíñïîðòåðû èç ñåìåéñòâà îðãàíè÷åñêèõ êàòèîíî⠗ OCT1, OCT2 è OCT3, êîòîðûå èãðàþò âàæíóþ ðîëü âî âñàñûâàíèè, ðàñïðåäåëåíèè è àêòèâíîé ñåêðåöèè ãèäðîôèëüíûõ ËÑ â ìî÷ó [20]. Ëîïèíàâèð, íåëôèíàâèð, ñàêâèíàâèð ñíèæàþò ñåêðåòîðíóþ àêòèâíîñòü ïðîòåèíà ðåçèñòåíòíîñòè ðàêà ãðóäè (BCRP) òðàíñïîðòåðà
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    . Òàêèì îáðàçîì, âçàèìîäåéñòâèå ÀÐÂÏ ñ ðàçëè÷íûìè òðàíñïîðòåðàìè ËÑ èãðàåò âàæíóþ ðîëü â ìîäèôèêàöèè ôàðìàêîêèíåòè÷åñêèõ è ôàðìàêîäèíàìè÷åñêèõ ïðîöåññîâ è, ñîîòâåòñòâåííî, ýôôåêòèâíîñòè è áåçîïàñíîñòè ÂÀÐÂÒ [22].

22
Gulati A, Gerk PM. Role of placental ATP-binding cassette (ABC) trasporters in antiretroviral therapy during pregnanacy. J Pharm Sci. 2009; 98(7): 2317–35. AUTHORS Federal State Budgetary Institution «Scientific Centre for Expert Evaluation of Medicinal Products» of the Ministry of Health
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    Òàêèì îáðàçîì, âçàèìîäåéñòâèå ÀÐÂÏ ñ ðàçëè÷íûìè òðàíñïîðòåðàìè ËÑ èãðàåò âàæíóþ ðîëü â ìîäèôèêàöèè ôàðìàêîêèíåòè÷åñêèõ è ôàðìàêîäèíàìè÷åñêèõ ïðîöåññîâ è, ñîîòâåòñòâåííî, ýôôåêòèâíîñòè è áåçîïàñíîñòè ÂÀÐÂÒ
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    . Íàïðèìåð, ðèòîíàâèð ÷àñòî âêëþ÷àþò â ñõåìû ÂÀÐÂÒ èç-çà ñïîñîáíîñòè èíãèáèðîâàòü ABC-òðàíñïîðòåðû è èçîôåðìåíòû ìåòàáîëèçìà öèòîõðîìà Ð450. Ýòî èíãèáèðîâàíèå ïðèâîäèò ê áîëåå âûñîêîé áèîäîñòóïíîñòè, áîëåå ìåäëåííîìó âûâåäåíèþ è, òàêèì îáðàçîì, ê ïîâûøåíèþ êîíöåíòðàöèè ñîâìåñòíî íàçíà÷àåìûõ ïðåïàðàòîâ.