The 12 references with contexts in paper V. Smirnov V., E. Egorenkov A., L. Krasnykh M., G. Vasilenko F., G. Ramenskaya V., В. Смирнов В., Е. Егоренков А., Л. Красных М., Г. Василенко Ф., Г. Раменская В. (2018) “Определение активности ферментов метаболизма лекарственных средств - перспектива использования в клинической практике // Determination of the activity of drug-metabolizing enzymes - the prospects for their use in clinical practice” / spz:neicon:vedomostincesmp:y:2016:i:4:p:28-32

1
Kukes VG. The metabolism of medicines: clinical and pharmacological aspects. Moscow: Reafarm; 2004 (in Russian).
Total in-text references: 3
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    Îäíàêî èçîôåðìåíòû öèòîõðîìà Ð450 ìîæíî îáíàðóæèòü è â äðóãèõ îðãàíàõ: êèøå÷íèêå, ïî÷êàõ, ëåãêèõ, íàäïî÷å÷íèêàõ, ãîëîâíîì ìîçãå, êîæå, ïëàöåíòå, ìèîêàðäå. Âàæíåéøèì ñâîéñòâîì öèòîõðîìà Ð450 ÿâëÿåòñÿ ñïîñîáíîñòü ìåòàáîëèçèðîâàòü ïðàêòè÷åñêè âñå èçâåñòíûå õèìè÷åñêèå ñîåäèíåíèÿ. Íàèáîëåå âàæíîé ðåàêöèåé ïðè ýòîì ÿâëÿåòñÿ ãèäðîêñèëèðîâàíèå
    Exact
    [1]
    Suffix
    . Öèòîõðîì Ð450 èìååò ìíîæåñòâî èçîôîðì — èçîôåðìåíòîâ, êîòîðûõ íà äàííûé ìîìåíò âûäåëåíî áîëåå 1000. Èçîôåðìåíòû öèòîõðîìà Ð450 ïî êëàññèôèêàöèè Nebert (1987) ïðèíÿòî ðàçäåëÿòü ïî áëèçîñòè (ãîìîëîãèè) íóêëåîòèä/àìèíîêèñëîòíîé ïîñëåäîâàòåëüíîñòè íà ñåìåéñòâà, à ïîñëåäíèå, â ñâîþ î÷åðåäü, íà ïîäñåìåéñòâà.

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    Íåñìîòðÿ íà âñå îáèëèå ñóùåñòâóþùèõ ôåðìåíòîâ ìåòàáîëèçìà, íåïîñðåäñòâåííî â ìåòàáîëèçìå ëåêàðñòâåííûõ ñðåäñòâ ãëàâíóþ ðîëü èãðàþò íå áîëåå 10 èçîôåðìåíòîâ CYP, ïðè ýòîì äàííûå èçîôåðìåíòû îòâå÷àþò çà ìåòàáîëèçì ïðàêòè÷åñêè âñåõ èçâåñòíûõ ëåêàðñòâåííûõ ñðåäñòâ, à èìåííî 95 %
    Exact
    [1–3]
    Suffix
    . Òàê, íàïðèìåð, âêëàä îäíîãî èç èçîôåðìåíòîâ, CYP3A4, â îáùèå ïðîöåññû ìåòàáîëèçìà ñîñòàâëÿåò 35 %, ïðè ýòîì îí ìåòàáîëèçèðóåò ëåêàðñòâåííûå ñðåäñòâà ðàçëè÷íûõ ôàðìàêîëîãè÷åñêèõ ãðóïï. Îñòàëüíûå èçîôåðìåíòû èìåþò áîëåå óçêèé íàáîð ñïåöèôè÷íûõ âåùåñòâ-ñóáñòðàòîâ, îäíàêî ïðîöåíò èõ âêëàäà â ìåòàáîëèçì òàêæå çíà÷èòåëåí.

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    Ñâÿçûâàÿñü ñ áåëêàìè ïëàçìû ïðàêòè÷åñêè ïîëíîñòüþ (94–99 %), îí ìåòàáîëèçèðóåòñÿ èçîôåðìåíòîì CYP3A4 ñ ïîÿâëåíèåì àêòèâíûõ ìåòàáîëèòîâ. Äàííîå ËÑ î÷åíü ÷àñòî èñïîëüçóþò â èññëåäîâàíèÿõ, ñâÿçàííûõ ñ èçó÷åíèåì àêòèâíîñòè êàêèõ-ëèáî èçîôåðìåíòîâ öèòîõðîìà P450, åñëè íåîáõîäèìî ñíèçèòü àêòèâíîñòü CYP3A4
    Exact
    [1, 12]
    Suffix
    . Ëîâàñòàòèí — ãèïîëèïèäåìè÷åñêîå ñðåäñòâî èç ãðóïïû ñòàòèíîâ, èíãèáèòîð ÃÌÃ-ÊîÀ-ðåäóêòàçû. ßâëÿåòñÿ ïðîëåêàðñòâîì, ïîñêîëüêó èìååò â ñâîåé ñòðóêòóðå çàêðûòîå ëàêòîíîâîå êîëüöî, êîòîðîå ïîñëå ïîñòóïëåíèÿ â îðãàíèçì ãèäðîëèçóåòñÿ.

2
Kukes VG, Bochkov NP, eds. Clinical pharmacogenetics. Moscow: GEOTAR; 2007 (in Russian).
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    öèòîõðîìà Ð450 ïî êëàññèôèêàöèè Nebert (1987) ïðèíÿòî ðàçäåëÿòü ïî áëèçîñòè (ãîìîëîãèè) íóêëåîòèä/àìèíîêèñëîòíîé ïîñëåäîâàòåëüíîñòè íà ñåìåéñòâà, à ïîñëåäíèå, â ñâîþ î÷åðåäü, íà ïîäñåìåéñòâà. Òàêèì îáðàçîì, íà ñåãîäíÿøíèé äåíü íàñ÷èòûâàåòñÿ îêîëî 36 ñåìåéñòâ è 29 ïîäñåìåéñòâ. Ó êàæäîãî èçîôåðìåíòà CYP èìåþòñÿ ñâîÿ ðîëü â ïðîöåññå ìåòàáîëèçìà êñåíîáèîòèêîâ è ñâîé ñïåöèôè÷åñêèé ñóáñòðàò
    Exact
    [2]
    Suffix
    . Íåñìîòðÿ íà âñå îáèëèå ñóùåñòâóþùèõ ôåðìåíòîâ ìåòàáîëèçìà, íåïîñðåäñòâåííî â ìåòàáîëèçìå ëåêàðñòâåííûõ ñðåäñòâ ãëàâíóþ ðîëü èãðàþò íå áîëåå 10 èçîôåðìåíòîâ CYP, ïðè ýòîì äàííûå èçîôåðìåíòû îòâå÷àþò çà ìåòàáîëèçì ïðàêòè÷åñêè âñåõ èçâåñòíûõ ëåêàðñòâåííûõ ñðåäñòâ, à èìåííî 95 % [1–3].

4
Hocum BT, White JR, Heck JW, Thirumaran RK, Moyer N, Newman R, Ashcraft K. Cytochrome P450 gene and drug interaction analysis in patients referred for pharmacogenetic testing. Am J Health Syst Pharm. 2016; 73(2): 61–7.
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    Ðÿä ôàðìàêîãåíåòè÷åñêèõ èññëåäîâàíèé ïîçâîëèë ñíèçèòü ðèñê âîçíèêíîâåíèÿ íåæåëàòåëüíûõ ðåàêöèé âñëåäñòâèå ïåðåäîçèðîâêè ïðåïàðàòàìè ñ óçêèì òåðàïåâòè÷åñêèì îêíîì, êàê, íàïðèìåð, âàðôàðèí, íåêîòîðûå ïñèõîàêòèâíûå ËÑ è äð.
    Exact
    [4]
    Suffix
    . Îñíîâíûìè íåäîñòàòêàìè ãåíîòèïè÷åñêîãî ìåòîäà îïðåäåëåíèÿ àêòèâíîñòè èçîôåðìåíòîâ CYP ÿâëÿåòñÿ òî, ÷òî äàííûå îá àêòèâíîñòè ñîáèðàþòñÿ áåç ó÷åòà âëèÿíèÿ îêðóæàþùèõ ôàêòîðîâ íà îðãàíèçì. Ïîñêîëüêó ãåíåòè÷åñêàÿ èíôîðìàöèÿ íå ìåíÿåòñÿ âî âðåìåíè, òî è àêòèâíîñòü ôåðìåíòîâ, îïðåäåëÿåìàÿ ìåòîäîì ãåíîòèïèðîâàíèÿ, íå ìåíÿåòñÿ âî âðåìåíè.

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    ìíîãèõ ËÑ ðàçíûõ ôàðìàêîëîãè÷åñêèõ ãðóïï: íåñòåðîèäíûå ïðîòèâîâîñïàëèòåëüíûå ïðåïàðàòû (ÍÏÂÏ), àíòèêîàãóëÿíòû, ïåðîðàëüíûå ãèïîãëèêåìè÷åñêèå ñðåäñòâà è äð. ×èñëî «ìåäëåííûõ »ìåòàáîëèçàòîðîâ ïî ýòîìó èçîôåðìåíòó ñîñòàâëÿåò ïðèìåðíî 1–3 % ñðåäè åâðîïåéöåâ è 5 % ñðåäè ðîññèÿí, ÷òî îáóñëîâëèâàåò âîçíèêíîâåíèå íåæåëàòåëüíûõ ðåàêöèé ó ýòèõ ëþäåé ïî ïðè÷èíå äàííîé îñîáåííîñòè èõ îðãàíèçìà
    Exact
    [4]
    Suffix
    .  êà÷åñòâå âåùåñòâà-ñóáñòðàòà äàííîãî èçîôåðìåíòà áûë âûáðàí ëîçàðòàí — ëåêàðñòâåííîå ñðåäñòâî, äèóðåòèê, èíãèáèòîð ðåöåïòîðîâ àíãèîòåíçèíà II òèïà. Äàííûé ïðåïàðàò áûë âûáðàí â ñâÿçè ñ åãî îòíîñèòåëüíîé äåøåâèçíîé, áåçîïàñíîñòüþ è âîçìîæíîñòüþ ìàêñèìàëüíî òî÷íî îïðåäåëèòü åãî êîíöåíòðàöèþ â áèîæèäêîñòÿõ îðãàíèçìà.

5
Samer CF, Lorenzini KI, Rollason V, Daali Y, Desmeules JA. Applications of CYP450 testing in the clinical setting. Mol Diagn Ther. 2013; 17(3): 165–84.
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    Ïîñêîëüêó ãåíåòè÷åñêàÿ èíôîðìàöèÿ íå ìåíÿåòñÿ âî âðåìåíè, òî è àêòèâíîñòü ôåðìåíòîâ, îïðåäåëÿåìàÿ ìåòîäîì ãåíîòèïèðîâàíèÿ, íå ìåíÿåòñÿ âî âðåìåíè. Òàêèì îáðàçîì, äàííûå ãåíîòèïèðîâàíèÿ íåîáõîäèìî ïîäòâåðæäàòü èçó÷åíèåì àêòèâíîñòè ôåðìåíòîâ ìåòàáîëèçìà â ðåàëüíîì, òåêóùåì âðåìåíè
    Exact
    [5]
    Suffix
    . Ñóáñòðàòíàÿ ñïåöèôè÷íîñòü îïðåäåëåííûõ ôåðìåíòîâ ìåòàáîëèçìà ËÑ ïîçâîëèëà ðàçðàáîòàòü ìåòîäû èõ ôåíîòèïèðîâàíèÿ. Àêòèâíîñòü òîãî èëè èíîãî ôåðìåíòà ìåòàáîëèçìà îïðåäåëÿåòñÿ ïî ôàðìàêîêèíåòèêå åãî ñïåöèôè÷åñêîãî ñóáñòðàòà, íàçûâàåìîãî «ìàðêåðíûì »ñóáñòðàòîì, ïóòåì èçìåðåíèÿ åãî êîíöåíòðàöèè è êîíöåíòðàöèè åãî ìåòàáîëèòà â ïëàçìå êðîâè èëè â ìî÷å.

6
Khojasteh SC, Prabhu S, Kenny JR, Halladay JS, Lu AY. Chemical inhibitors of cytochrome P450 isoforms in human liver microsomes: a re-evaluation of P450 isoform selectivity. Eur J Drug Metab Pharmacokinet. 2011; 36(1): 1–16.
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    Íà îñíîâàíèè ýòèõ äàííûõ ðàññ÷èòûâàåòñÿ òàê íàçûâàåìûé «ìåòàáîëè÷åñêèé »èíäåêñ, ðàâíûé îòíîøåíèþ êîíöåíòðàöèè ËÑ ê êîíöåíòðàöèè åãî ìåòàáîëèòà, êîòîðûé íåïîñðåäñòâåííî äàåò èíôîðìàöèþ îá àêòèâíîñòè ñîîòâåòñòâóþùåãî ôåðìåíòà ìåòàáîëèçìà
    Exact
    [6]
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    . Ôåíîòèïèðîâàíèå ïîçâîëÿåò, èçó÷àÿ äèíàìèêó êîíöåíòðàöèè ËÑ îäíîâðåìåííî ñ èõ ìåòàáîëèòàìè, îïðåäåëèòü, ñâÿçàíî ëè çíà÷èòåëüíîå îòêëîíåíèå êîíöåíòðàöèè ËÑ â êðîâè ó ïàöèåíòà (îò ñðåäíèõ òåðàïåâòè÷åñêèõ çíà÷åíèé) ñ èçìåíåíèÿìè íà ñòàäèè âñàñûâàíèÿ ëåêàðñòâåííîãî ïðåïàðàòà èëè íà ñòàäèè åãî ìåòàáîëèçìà.

7
Emoto C, Murayama N, Rostami-Hodjegan A, Yamazaki H. Methodologies for investigating drug metabolism at the early drug discovery stage: prediction of hepatic drug clearance and P450 contribution. Curr Drug Metab. 2010; 11(8): 678–85.
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    Ôåíîòèïèðîâàíèå ïîçâîëÿåò àíàëèçèðîâàòü âîçìîæíîñòü âçàèìîäåéñòâèÿ íåñêîëüêèõ ËÑ ïðè èõ ñîâìåñòíîì ïðèìåíåíèè çà ñ÷åò ïåðåêðåñòíîãî óâåëè÷åíèÿ èëè óìåíüøåíèÿ àêòèâíîñòè ðàçëè÷íûõ ôåðìåíòîâ ìåòàáîëèçìà. Ïîìèìî ïðî÷åãî, ôåíîòèïèðîâàíèå ïîçâîëÿåò îïðåäåëèòü ñòåïåíü âëèÿíèÿ îòäåëüíûõ ïèùåâûõ ïðîäóêòîâ, íàïèòêîâ, êóðåíèÿ è ïðî÷èõ âíåøíèõ ôàêòîðîâ íà àêòèâíîñòü èçîôåðìåíòîâ öèòîõðîìà Ð450
    Exact
    [7, 8]
    Suffix
    . Òàêèì îáðàçîì, íàèáîëåå ïîëíóþ è èíôîðìàòèâíóþ êàðòèíó àêòèâíîñòè èçîôåðìåíòîâ öèòîõðîìà Ð450 ïðåäîñòàâëÿåò ìåòîä ôåíîòèïèðîâàíèÿ. Àâòîðàìè áûë ðàçðàáîòàí ðÿä ôåíîòèïè÷åñêèõ ìåòîäèê îïðåäåëåíèÿ àêòèâíîñòè ðàçëè÷íûõ èçîôåðìåíòîâ CYP (êàê ñîâìåñòíî íåñêîëüêèõ èçîôåðìåíòîâ, òàê è ïî îòäåëüíîñòè).

8
Spaggiari D, Geiser L, Daali Y, Rudaz S. A cocktail approach for assessing the in vitro activity of human cytochrome P450s: an overview of current methodologies. J Pharm Biomed Anal. 2014; 101: 221–37.
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    Ôåíîòèïèðîâàíèå ïîçâîëÿåò àíàëèçèðîâàòü âîçìîæíîñòü âçàèìîäåéñòâèÿ íåñêîëüêèõ ËÑ ïðè èõ ñîâìåñòíîì ïðèìåíåíèè çà ñ÷åò ïåðåêðåñòíîãî óâåëè÷åíèÿ èëè óìåíüøåíèÿ àêòèâíîñòè ðàçëè÷íûõ ôåðìåíòîâ ìåòàáîëèçìà. Ïîìèìî ïðî÷åãî, ôåíîòèïèðîâàíèå ïîçâîëÿåò îïðåäåëèòü ñòåïåíü âëèÿíèÿ îòäåëüíûõ ïèùåâûõ ïðîäóêòîâ, íàïèòêîâ, êóðåíèÿ è ïðî÷èõ âíåøíèõ ôàêòîðîâ íà àêòèâíîñòü èçîôåðìåíòîâ öèòîõðîìà Ð450
    Exact
    [7, 8]
    Suffix
    . Òàêèì îáðàçîì, íàèáîëåå ïîëíóþ è èíôîðìàòèâíóþ êàðòèíó àêòèâíîñòè èçîôåðìåíòîâ öèòîõðîìà Ð450 ïðåäîñòàâëÿåò ìåòîä ôåíîòèïèðîâàíèÿ. Àâòîðàìè áûë ðàçðàáîòàí ðÿä ôåíîòèïè÷åñêèõ ìåòîäèê îïðåäåëåíèÿ àêòèâíîñòè ðàçëè÷íûõ èçîôåðìåíòîâ CYP (êàê ñîâìåñòíî íåñêîëüêèõ èçîôåðìåíòîâ, òàê è ïî îòäåëüíîñòè).

9
Lo MW, Goldberg MR, McCrea JB, Lu H, Furtek CI, Bjornsson TD. Pharmacokinetics of losartan, an angiotensin II receptor antagonist, and its active metabolite EXP3174 in humans. Clin Pharmacol Ther. 1995; 58(6): 641–9.
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    Äàííûé ïðåïàðàò áûë âûáðàí â ñâÿçè ñ åãî îòíîñèòåëüíîé äåøåâèçíîé, áåçîïàñíîñòüþ è âîçìîæíîñòüþ ìàêñèìàëüíî òî÷íî îïðåäåëèòü åãî êîíöåíòðàöèþ â áèîæèäêîñòÿõ îðãàíèçìà.  ïðîöåññå ìåòàáîëèçìà (ðèñ. 1) ïîä äåéñòâèåì èçîôåðìåíòà CYP2C9 ëîçàðòàí ïðåâðàùàåòñÿ â ñâîé ìåòàáîëèò — ëîçàðòàíîâóþ êèñëîòó, èëè Å-3174
    Exact
    [9]
    Suffix
    . Âàæíóþ ðîëü â ìåòàáîëèçìå ëîçàðòàíà èãðàåò òàêæå èçîôåðìåíò CYP3A4, ìåòàáîëèçèðóÿ íåêîòîðóþ äîëþ ëîçàðòàíà, ïîýòîìó ñóäèòü îá àêòèâíîñòè CYP2C9 ëèøü ïî ìåòàáîëè÷åñêîìó èíäåêñó ïàðû ëîçàðòàí/E-3174 íåâåðíî; íåîáõîäèìî òàêæå îïðåäåëèòü àêòèâíîñòü èçîôåðìåíòà CYP3A4 è ïðîâåñòè êîððåêòèðîâêó ðàññ÷åòîâ.

10
Stearns RA, Chakravarty PK, Chen R, Chiu SH. Biotransformation of losartan to its active carboxylic acid metabolite in human liver microsomes. Role of cytochrome P4502C and 3A subfamily members. Drug metabolism and disposition: the biological fate of chemicals. Drug Metab Dispos. 1995; 23(2): 207–15.
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    Äëÿ îïðåäåëåíèÿ àêòèâíîñòè èçîôåðìåíòà CYP3A4 èñïîëüçóåòñÿ êîðòèçîë, ÿâëÿþùèéñÿ ýíäîãåííûì âåùåñòâîì-ñóáñòðàòîì äàííîãî èçîôåðìåíòà. Êîðòèçîë ïîä âëèÿíèåì CYP3A4 ìåòàáîëèçèðóåòñÿ â 6-b-ãèäðîêñèêîðòèçîë
    Exact
    [10, 11]
    Suffix
    . Áûëà ðàçðàáîòàíà ìåòîäèêà ñîâìåñòíîãî êîëè÷åñòâåííîãî îïðåäåëåíèÿ âûøåïåðå÷èñëåííûõ âåùåñòâ â ìî÷å ìåòîäîì âûñîêîýôôåêòèâíîé æèäêîñòíîé õðîìàòîãðàôèè (ÂÝÆÕ) ñ ìàññ-ñïåêòðîìåòðè÷åñêèì äåòåêòèðîâàíèåì.

11
Yun CH, Lee HS, Lee H, Rho JK, Jeong HG, Guengerich FP. Oxidation of the angiotensin II receptor antagonist losartan (DuP 753) in human liver microsomes. Role of cytochrome P4503A(4) in formation of the active metabolite EXP3174. Drug Metab Dispos. 1995; 23(2): 207–15.
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    Äëÿ îïðåäåëåíèÿ àêòèâíîñòè èçîôåðìåíòà CYP3A4 èñïîëüçóåòñÿ êîðòèçîë, ÿâëÿþùèéñÿ ýíäîãåííûì âåùåñòâîì-ñóáñòðàòîì äàííîãî èçîôåðìåíòà. Êîðòèçîë ïîä âëèÿíèåì CYP3A4 ìåòàáîëèçèðóåòñÿ â 6-b-ãèäðîêñèêîðòèçîë
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    [10, 11]
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    . Áûëà ðàçðàáîòàíà ìåòîäèêà ñîâìåñòíîãî êîëè÷åñòâåííîãî îïðåäåëåíèÿ âûøåïåðå÷èñëåííûõ âåùåñòâ â ìî÷å ìåòîäîì âûñîêîýôôåêòèâíîé æèäêîñòíîé õðîìàòîãðàôèè (ÂÝÆÕ) ñ ìàññ-ñïåêòðîìåòðè÷åñêèì äåòåêòèðîâàíèåì.

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Choi JS, Choi I, Choi DH. Effects of nifedipine on the pharmacokinetics of repaglinide in rats: possible role of CYP3A4 and P-glycoprotein inhibition by nifedipine. Pharmacol Rep. 2013; 65(5): 1422–30.
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    Ñâÿçûâàÿñü ñ áåëêàìè ïëàçìû ïðàêòè÷åñêè ïîëíîñòüþ (94–99 %), îí ìåòàáîëèçèðóåòñÿ èçîôåðìåíòîì CYP3A4 ñ ïîÿâëåíèåì àêòèâíûõ ìåòàáîëèòîâ. Äàííîå ËÑ î÷åíü ÷àñòî èñïîëüçóþò â èññëåäîâàíèÿõ, ñâÿçàííûõ ñ èçó÷åíèåì àêòèâíîñòè êàêèõ-ëèáî èçîôåðìåíòîâ öèòîõðîìà P450, åñëè íåîáõîäèìî ñíèçèòü àêòèâíîñòü CYP3A4
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    [1, 12]
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    . Ëîâàñòàòèí — ãèïîëèïèäåìè÷åñêîå ñðåäñòâî èç ãðóïïû ñòàòèíîâ, èíãèáèòîð ÃÌÃ-ÊîÀ-ðåäóêòàçû. ßâëÿåòñÿ ïðîëåêàðñòâîì, ïîñêîëüêó èìååò â ñâîåé ñòðóêòóðå çàêðûòîå ëàêòîíîâîå êîëüöî, êîòîðîå ïîñëå ïîñòóïëåíèÿ â îðãàíèçì ãèäðîëèçóåòñÿ.

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Zong H, Zhuge B, Lu X, Huo X, Fang H, Song J, Sun J. Characterization of a novel cytochrome P450 from Amycolatopsis sp. CGMCC1149 for hydroxylation of lovastatin. Biotechnol Appl Biochem. 2015; 62(1): 9–16. AUTHORS
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    Ïîäâåðãàåòñÿ èíòåíñèâíîìó ìåòàáîëèçìó ïðè «ïåðâè÷íîì ïðîõîæäåíèè »÷åðåç ïå÷åíü, îêèñëÿÿñü äî íåñêîëüêèõ ìåòàáîëèòîâ, ÷àñòü èç êîòîðûõ ôàðìàêîëîãè÷åñêè àêòèâíà. Îñíîâíûì ôåðìåíòîì â ýòèõ ïðîòåêàþùèõ ðåàêöèÿõ ÿâëÿåòñÿ èçîôåðìåíò CYP2C9
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    [13]
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    . Ïîñëåäîâàòåëüíîñòü îòáîðà îáðàçöîâ ïðîá ìî÷è ó ïàöèåíòîâ.Ïåðâûé îòáîð ïðîá ïðîâîäèëè â ìîìåíò ïîñòóïëåíèÿ ïàöèåíòà â ñòàöèîíàð äî íà÷àëà ôàðìàêîòåðàïèè. Âå÷åðîì íàêàíóíå èññëåäîâàíèÿ ïàöèåíò ïðèíèìàë òàáëåòêó ëîçàðòàíà (äîçà 50 ìã), çàïèâàÿ îäíèì ñòàêàíîì âîäû.