{"id":9959,"date":"2020-04-23T03:52:24","date_gmt":"2020-04-23T00:52:24","guid":{"rendered":"https:\/\/www.synevo.ro\/product\/variante-genetice-enzima-cyp2d6-citocrom-p450\/"},"modified":"2025-01-31T11:37:36","modified_gmt":"2025-01-31T09:37:36","slug":"variante-genetice-enzima-cyp2d6-citocrom-p450","status":"publish","type":"product","link":"https:\/\/old.synevo.md\/ru\/shop\/variante-genetice-enzima-cyp2d6-citocrom-p450\/","title":{"rendered":"\u0413\u0435\u043d\u0435\u0442\u0438\u0447\u0435\u0441\u043a\u0438\u0435 \u0432\u0430\u0440\u0438\u0430\u043d\u0442\u044b \u0444\u0435\u0440\u043c\u0435\u043d\u0442\u0430 CYP2D6 (\u0446\u0438\u0442\u043e\u0445\u0440\u043e\u043c P450)"},"content":{"rendered":"

\u041e\u0431\u0449\u0430\u044f \u0438\u043d\u0444\u043e\u0440\u043c\u0430\u0446\u0438\u044f <\/em><\/strong><\/p>\n

CYP2D6 este o enzima ce face parte din marea familie a citocromului P450 (familia 2, subfamilia D) implicata in metabolizarea a 25% dintre medicamentele administrate, printre care se numara codeina, antidepresivele triciclice (de exempu, nortriptilina), inhibitori selectivi ai recaptarii serotoninei (SSRI: fluvoxamin), inhibitori ai recaptarii serotoninei-norepinefrinei (SSNRI: venlafaxina), antipsihotice clasice (haloperidol), beta-blocante. Anumite variante ale acestei enzime influenteaza si metabolismul tamoxifenului la femeile cu cancer mamar in perioada de postmenopauza2<\/sup>.<\/p>\n

Tamoxifenul este larg utilizat in terapia hormonala a pacientelor cu tumori mamare pozitive pentru receptorii estrogenului (ER). Beneficiul sau clinic a fost constatat de mai bine de trei decade, atat in tratamentul adjuvant al formelor avansate de boala debutate inainte de menopauza cat si ca optiune valida, alaturi de inhibitorii de aromataza, in perioada de postmenopauza. Totusi, aproximativ o treime din pacientele tratate cu tamoxifen prezinta o recurenta a bolii in decurs de 15 ani de la interventia chirurgicala. Se descrie de asemenea o variatie inter-individuala semnificativa atat in ceea ce priveste efectul terapeutic cat si reactiile adverse4<\/sup>.<\/p>\n

Tamoxifenul este un modulator selectiv al receptorului pentru estrogen (SERM). Date recente au indicat faptul ca eficacitatea tamoxifenului depinde de biotransformarea, predominant cu ajutorul enzimei CYP2D6, in metabolitul sau activ endoxifen <\/em>care are o afinitate mai mare pentru receptorul estrogenului si un efect anti-estrogenic mai potent decat tamoxifenul. La radul sau, activitatea CYP2D6 este extrem de variabila ca urmare a polimorfismului genei care codifica enzima si a inhibitorilor CYP2D6 utilizati ca medicatie asociata4<\/sup>.<\/p>\n

CYP2D6\u00a0 se exprima in principal la nivel hepatic; au fost descrise pana in prezent peste 100 polimorfisme \u2013 variante alelice \u2013 asociate cu activitate enzimatica crescuta, scazuta sau absenta (vezi tabelul 18.2.4.1<\/em>).<\/p>\n\n\n\n\n\n\n\n\n
\n

Alele CYP2D6<\/strong><\/p>\n<\/td>\n

\n

Activitate enzimatica<\/strong><\/p>\n<\/td>\n<\/tr>\n

\n

*1,\u00a0 *2,\u00a0 *33, *35<\/p>\n<\/td>\n

\n

Normala<\/p>\n<\/td>\n<\/tr>\n

\n

*3,*4,*5,*6,*7,*8,*11-*16, *18,<\/p>\n

*19,*20,*21, *36, *38,*40, *42, *44,<\/p>\n

*56, *62, 4xn, 6xn, 36xn<\/p>\n<\/td>\n

\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0 Absenta<\/td>\n<\/tr>\n
\n

*9,*10, *17, *29, *41, *69, 29xn si<\/p>\n

41xn<\/p>\n<\/td>\n

\n

Scazuta<\/p>\n<\/td>\n<\/tr>\n

\n

*22,*23-*28, *30-*32, *34,*37,*39,<\/p>\n

*43,*45-*68, *70-*75<\/p>\n<\/td>\n

\n

Necunoscuta<\/p>\n<\/td>\n<\/tr>\n

\n

*1xn, *2xn,*35xn<\/p>\n<\/td>\n

\n

Crescuta<\/p>\n<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

Tabel 18.2.4.1 Alelele CYP2D6 si efectul acestora asupra activitatii enzimatice<\/span><\/p>\n

\u00a0<\/span><\/p>\n

Acestea confera diferite fenotipuri cu urmatoarea prevalenta in populatia caucaziana: metabolizator\u00a0 <\/em>lent<\/em> (7-10%), intermediar<\/em> (10-15%), ultrarapid<\/em> (10-15%) si extensiv (normal)<\/em>. Activitatea crescuta rezulta prin duplicatia genei CYP2D6, in timp ce activitatea redusa\/absenta este consecinta unor deletii, mutatii ale codonului STOP sau defecte de splicing4<\/sup>.<\/p>\n

Polimorfismele asociate cu fenotipul de \u201emetabolizator lent\u201d sunt autozomal recesive; din acest motiv numai statusul\u00a0 homozigot sau heterozigot compus pentru aceste polimorfisme confera fenotipul de \u201emetabolizator lent\u201d asociat cu niveluri inadecvate de endoxifen la pacientele cu cancer mamar care primesc tratament cu tamoxifen si, din acest motiv, cu un risc mai mare de recurenta a bolii3<\/sup>.<\/p>\n

Cele mai frecvente variante alelice sunt CYP2D6*4 <\/em>(12\u201321% la caucazieni), CYP2D6*5 <\/em>(~ 2\u20137% in diferite populatii), CYP2D6*10 <\/em>(>50% la asiatici, 5-9% la africani), CYP2D6*17 <\/em>(20\u201335% la africani si and americani de origine africana).<\/p>\n

Prima evidenta clinica a asocierii statusului de \u201emetabolizator lent\u201d cu raspunsul suboptimal la tratamentul cu tamoxifen a fost raportat de Goetz et al in 2005 in urma unui studiu efectuat pe 223 femei cu cancer mamar ER pozitiv in perioada postmenopauza, tratate cu tamoxifen. Desi a fost subestimata frecventa metabolizatorilor lenti, prin includerea doar a alelelor CYP2D6*4 <\/em>si CYP2D6*6<\/em>, autorii au aratat ca alela CYP2D6*4 <\/em>a fost asociata cu un risc crescut de recadere si cu o incidenta mai scazuta a bufeurilor la pacientele postmenopauza (o reactie adversa frecvent intalnita in cursul tratamentului cu tamoxifen) datorita nivelurilor mai scazute de metaboliti activi.<\/p>\n

Din 2005 pana in prezent au fost publicate cateva studii privind impactul genotipului CYP2D6 asupra evolutiei pacientelor aflate sub tamoxifen care insa au raportat rezultate contradictorii. Pentru a explica aceste discrepante au fost propuse mai multe explicatii: numarului redus de persoane incluse in unele studii, populatii disparate de paciente, diferente in ceea ce priveste doza si durata tratamentului cu tamoxifen, lipsa de informatii despre medicatia asociata, metode diferite pentru genotiparea CYP2D6.<\/p>\n

In ultimii 25 ani, tamoxifenul a fost considerat \u201egold-standard\u201d pentru tratamentul hormonal al cancerului mamar ER pozitiv. Totusi, rezultatele unor studii clinice recente au demonstrat ca, in unele situatii, inhibitorii de aromataza de generatia a 3-a (anastrozol, letrozol, exemestan) sunt mai eficace decat tamoxifenul in tratmentul pacientelor postmenopauza. Goetz et al au examinat un set de femei postmenopauza tratate in cadrul studiului ABCSG-8 si au evaluat efectul inlocuirii tamoxifenului administrat timp de 2 ani cu anastrozol pe o perioada de 3 ani. Printre pacientele tratate timp de cinci ani numai cu tamoxifen, metabolizatorii lenti au avut un risc de 3.8 ori mai mare de recurenta a tumorii in comparatie cu metabolizatorii extensivi. La pacientele care au fost trecute pe anastrozol dupa 2 ani de tamoxifen nu s-a constatat un risc crescut de recadere in cazul fenotipului de \u201emetabolizator lent\u201d, ceea ce sugereaza ca beneficiul comutarii pe anastrozol ar fi mai pronuntat la persoanele cu deficit enzimatic CYP2D6. Alegerea optima pentru terapia endocrina adjuvanta s-ar putea baza astfel pe genotipul CYP2D6. Presupunand ca metabolismul inhibitorilor de aromataza este independent de CYP2D6, studiile au aratat ca la pacientele cu genotip salbatic CYP2D6 rata de supravietuire este similara sau chiar superioara cu tamoxifen, in comparatie cu inhibitorii de aromataza. S-ar putea institui astfel o terapie personalizata bazata pe farmacogenetica in cazul pacientelor care sunt preocupate de relativa toxicitate a anastrozolului sau pentru a reduce costurile asociate cu administrarea de inhibitor de aromataza ca terapie initiala.<\/p>\n

Recent, analiza unor cohorte mari din SUA, Germania si Marea Britanie a intarit ipoteza potrivit careia exista o corelatie intre genotipul CYP2D6 si evolutia clinica sub tamoxifen. Dimpotriva, analiza ITPC (International Tamoxifen Pharmacogenetics Consortium) a demonstrat ca nu exista nici o asociere intre genotipul CYP2D6 si rata de supravietuire a pacientelor cu cancer mamar aflate sub tamoxifen. Desi ITPC a colectat cele mai multe de date privind genotipul CYP2D6 in terapia adjuvanta cu tamoxifen, aceasta reprezinta doar o analiza preliminara in care un numar mare de persoane au fost excluse din evaluarea primara ca urmare a unor probleme metodologice, a lipsei de informatii privind dozele, durata tratamentului cu tamoxifen precum si a co-medicatiei sau a urmaririi inadecvate a pacientelor. Din acest motiv, sunt asteptate cu interes rezultatele viitoare ale ITPC impreuna cu cele ale trialurilor randomizate tamoxifen versus inhibitori de aromataza, deoarece acestea vor putea stabili, cu precizie mai mare, valoarea determinarii genotipului CYP2D6 in tratmentul adjuvant personalizat4<\/sup>.<\/p>\n

Recomandari pentru genotiparea CYP2D6 <\/em><\/strong>- <\/em>stabilirea genotipului CYP2D6 \u00a0inaintea inceperii tratamentului cu tamoxifen3<\/sup>.\u00a0<\/em><\/strong><\/p>\n

Pregatire pacient<\/em><\/strong> \u2013 nu este necesara o pregatire speciala1<\/sup>.<\/p>\n

Specimen recoltat<\/em><\/strong> \u2013 sange venos1<\/sup>.<\/p>\n

Recipient de recoltare<\/em><\/strong>\u00a0\u2013 vacutainer ce contine EDTA ca anticoagulant1<\/sup>.<\/p>\n

Cantitate recoltata <\/em><\/strong>\u2013 cat permite vacuumul1<\/sup>.<\/p>\n

Cauze de respingere<\/em><\/strong> a probei <\/em><\/strong>\u2013 folosirea heparinei ca anticoagulant; probe coagulate sau hemolizate1<\/sup>.<\/p>\n

Stabilitate proba<\/em><\/strong> - 7 zile<\/em> la 2-8\u00baC1<\/sup>.<\/p>\n

Metoda<\/em><\/strong> - reactie de polimerizare in lant (PCR) si secventiere a genei CYP2D6<\/span>1<\/sup>.<\/p>\n

Raportarea si interpretarea rezultatelor<\/em><\/strong><\/p>\n

Se va comunica genotipul CYP2D6 obtinut si fenotipul de metabolizare asociat (conform tabelului de mai sus)1<\/sup>.<\/p>\n

Numeroase medicamente sau metaboliti ai acestora sunt inhibitori ai activitatii catalitice CYP2D6:<\/p>\n

\u2022 unele antidepresive triciclice sau SSRI (in special fluoxetin si paroxetin);<\/p>\n

\u2022 chinidina, amiodarona;<\/p>\n

\u2022 cimetidina;<\/p>\n

\u2022 celecoxib;<\/p>\n

\u2022 ritonavir.<\/p>\n

Asocierea tamoxifenului cu medicamente inhibitorii CYP2D6 poate induce un fenotip de \u201emetabolizator lent\u201d chiar daca genotipul CYP2D6 sugereaza o activitate enzimatica normala sau intermediara. Din acest motiv este foarte important ca interpretarea rezultatelor sa se efectueze in contextul medicatiei asociate. Deoarece antidepresivele sunt recomandate adesea pentru calmarea bufeurilor este important sa se administreze medicamente care nu compromit activitatea CYP2D6 si nu reduc astfel eficacitatea tamoxifenului3<\/sup>.<\/p>\n

Limite si interferente<\/em><\/strong><\/p>\n

Inaintea de initierea unei terapii noi trebuie tinut cont de faptul ca exista si alti factori care pot influenta metabolismul medicamentelor cum ar fi: dieta, absorbtia digestiva, medicatia asociata si, nu in ultimul rand, complianta inadecvata a pacientului2<\/sup>.<\/p>\n

\u00a0<\/span><\/p>\n

\u0411\u0438\u0431\u043b\u0438\u043e\u0433\u0440\u0430\u0444\u0438\u044f<\/span><\/p>\n

1. Laborator Synevo. Referinte specifice tehnologiei de lucru utilizate 2007. Ref Type: Catalog.<\/span><\/p>\n

2. Laboratory Corporation of America. Directory of Services and Interpretive Guide. Tamoxifen P450 Genotyping. www.labcorp.com, 2010. Ref Type: Internet Communication.<\/span><\/p>\n

3. Mayo Clinic. Mayo Medical Laboratories. Test Catalog: . Cytochrome P450 2D6 Genotyping for Tamoxifen Hormonal Therapy. www.mayomedicallaboratories.com. Ref Type: Internet Communication.<\/span><\/p>\n

4. Roberta Ferraldeschi, William G. Newman. The Impact of CYP2D6 Genotyping on Tamoxifen Treatment. In <\/span>Pharmaceuticals 2010, 3, 1122-1138.<\/span><\/p>","protected":false},"excerpt":{"rendered":"

\u0426\u0438\u0442\u043e\u0445\u0440\u043e\u043c CYP2D6 – \u0444\u0435\u0440\u043c\u0435\u043d\u0442 \u0441\u0435\u043c\u0435\u0439\u0441\u0442\u0432\u0430 \u043f\u0435\u0447\u0435\u043d\u043e\u0447\u043d\u044b\u0445 \u0446\u0438\u0442\u043e\u0445\u0440\u043e\u043c\u043e\u0432 P450, \u043e\u0441\u043d\u043e\u0432\u043d\u043e\u0439 \u0444\u0443\u043d\u043a\u0446\u0438\u0435\u0439 \u043a\u043e\u0442\u043e\u0440\u043e\u0433\u043e \u044f\u0432\u043b\u044f\u0435\u0442\u0441\u044f \u043c\u0435\u0442\u0430\u0431\u043e\u043b\u0438\u0437\u043c \u043a\u0441\u0435\u043d\u043e\u0431\u0438\u043e\u0442\u0438\u043a\u043e\u0432. \u042d\u0442\u043e\u0442 CYP \u043e\u0442\u0432\u0435\u0447\u0430\u0435\u0442 \u0437\u0430 \u043c\u0435\u0442\u0430\u0431\u043e\u043b\u0438\u0437\u043c 25 % \u043b\u0435\u043a\u0430\u0440\u0441\u0442\u0432, \u0432\u043a\u043b\u044e\u0447\u0430\u044f \u0442\u0440\u0438\u0446\u0438\u043a\u043b\u0438\u0447\u0435\u0441\u043a\u0438\u0435 \u0430\u043d\u0442\u0438\u0434\u0435\u043f\u0440\u0435\u0441\u0441\u0430\u043d\u0442\u044b, \u043e\u043f\u0438\u043e\u0438\u0434\u044b \u0438 \u0431\u0435\u0442\u0430-\u0431\u043b\u043e\u043a\u0430\u0442\u043e\u0440\u044b, \u0430 \u0442\u0430\u043a\u0436\u0435 \u043c\u043d\u043e\u0433\u0438\u0435 \u0434\u0440\u0443\u0433\u0438\u0435. \u0422\u0430\u043a\u0438\u043c \u043e\u0431\u0440\u0430\u0437\u043e\u043c, \u043d\u0430\u043b\u0438\u0447\u0438\u0435 \u0432\u0430\u0440\u0438\u0430\u043d\u0442\u043e\u0432 \u0432 \u044d\u0442\u043e\u043c \u0433\u0435\u043d\u0435 \u0432\u043b\u0438\u044f\u0435\u0442 \u043d\u0430 \u0441\u043f\u043e\u0441\u043e\u0431\u043d\u043e\u0441\u0442\u044c \u043c\u0435\u0442\u0430\u0431\u043e\u043b\u0438\u0437\u0438\u0440\u043e\u0432\u0430\u0442\u044c \u043c\u043d\u043e\u0436\u0435\u0441\u0442\u0432\u043e \u0441\u043e\u0435\u0434\u0438\u043d\u0435\u043d\u0438\u0439.<\/p>\n

CYP P450 – \u044d\u0442\u043e \u0441\u0443\u043f\u0435\u0440\u0441\u0435\u043c\u0435\u0439\u0441\u0442\u0432\u043e \u0444\u0435\u0440\u043c\u0435\u043d\u0442\u043e\u0432, \u0443\u0447\u0430\u0441\u0442\u0432\u0443\u044e\u0449\u0438\u0445 \u0432 \u0444\u0435\u0440\u043c\u0435\u043d\u0442\u0430\u0442\u0438\u0432\u043d\u043e\u043c \u043e\u043a\u0438\u0441\u043b\u0435\u043d\u0438\u0438 \u0441\u0442\u0435\u0440\u043e\u0438\u0434\u043e\u0432, \u0436\u0438\u0440\u043d\u044b\u0445 \u043a\u0438\u0441\u043b\u043e\u0442, \u043a\u0441\u0435\u043d\u043e\u0431\u0438\u043e\u0442\u0438\u043a\u043e\u0432 \u0438 \u0434\u0440\u0443\u0433\u0438\u0445 \u0431\u0438\u043e\u0441\u0438\u043d\u0442\u0435\u0442\u0438\u0447\u0435\u0441\u043a\u0438\u0445 \u043f\u0443\u0442\u0435\u0439. \u042d\u0442\u0438 \u0444\u0435\u0440\u043c\u0435\u043d\u0442\u044b \u043f\u0440\u0435\u0432\u0440\u0430\u0449\u0430\u044e\u0442 \u043a\u0441\u0435\u043d\u043e\u0431\u0438\u043e\u0442\u0438\u043a\u0438 \u0432 \u0432\u043e\u0434\u043e\u0440\u0430\u0441\u0442\u0432\u043e\u0440\u0438\u043c\u044b\u0435 \u043f\u0440\u043e\u0438\u0437\u0432\u043e\u0434\u043d\u044b\u0435 \u0434\u043b\u044f \u043e\u0431\u043b\u0435\u0433\u0447\u0435\u043d\u0438\u044f \u0438\u0445 \u0432\u044b\u0432\u0435\u0434\u0435\u043d\u0438\u044f \u0438\u0437 \u043e\u0440\u0433\u0430\u043d\u0438\u0437\u043c\u0430. CYP2D6 \u0432 \u043e\u0441\u043d\u043e\u0432\u043d\u043e\u043c \u043e\u0431\u043d\u0430\u0440\u0443\u0436\u0438\u0432\u0430\u0435\u0442\u0441\u044f \u0432 \u043f\u0435\u0447\u0435\u043d\u0438, \u043d\u043e \u0442\u0430\u043a\u0436\u0435 \u043f\u0440\u0438\u0441\u0443\u0442\u0441\u0442\u0432\u0443\u0435\u0442 \u0432 \u0446\u0435\u043d\u0442\u0440\u0430\u043b\u044c\u043d\u043e\u0439 \u043d\u0435\u0440\u0432\u043d\u043e\u0439 \u0441\u0438\u0441\u0442\u0435\u043c\u0435, \u0432\u043a\u043b\u044e\u0447\u0430\u044f substantia nigra.<\/p>\n

CYP2D6 \u0443\u0447\u0430\u0441\u0442\u0432\u0443\u0435\u0442 \u0432 \u043c\u0435\u0442\u0430\u0431\u043e\u043b\u0438\u0437\u043c\u0435 \u043c\u043d\u043e\u0436\u0435\u0441\u0442\u0432\u0430 \u0448\u0438\u0440\u043e\u043a\u043e \u0438\u0441\u043f\u043e\u043b\u044c\u0437\u0443\u0435\u043c\u044b\u0445 \u043f\u0440\u0435\u043f\u0430\u0440\u0430\u0442\u043e\u0432, \u0442\u0430\u043a\u0438\u0445 \u043a\u0430\u043a \u0430\u043d\u0442\u0438\u0434\u0435\u043f\u0440\u0435\u0441\u0441\u0430\u043d\u0442\u044b (\u0430\u043c\u0438\u0442\u0440\u0438\u043f\u0442\u0438\u043b\u0438\u043d, \u0434\u043e\u043a\u0441\u0435\u043f\u0438\u043d, \u0438\u043c\u0438\u043f\u0440\u0430\u043c\u0438\u043d, \u0444\u043b\u0443\u043e\u043a\u0441\u0435\u0442\u0438\u043d, \u043f\u0430\u0440\u043e\u043a\u0441\u0435\u0442\u0438\u043d, \u043c\u0438\u0440\u0442\u0430\u0437\u0430\u043f\u0438\u043d \u0438 \u0434\u0440.), \u043e\u043f\u0438\u043e\u0438\u0434\u044b (\u043a\u043e\u0434\u0435\u0438\u043d, \u043a\u043e\u0434\u0435\u0438\u043d \u0438 \u0434\u0440.), \u043e\u043f\u0438\u043e\u0438\u0434\u044b (\u043a\u043e\u0434\u0435\u0438\u043d, \u0442\u0440\u0430\u043c\u0430\u0434\u043e\u043b, \u043e\u043a\u0441\u0438\u043a\u043e\u0434\u043e\u043d \u0438 \u0434\u0440.), \u0430\u043d\u0442\u0438\u043f\u0441\u0438\u0445\u043e\u0442\u0438\u043a\u0438 (\u0433\u0430\u043b\u043e\u043f\u0435\u0440\u0438\u0434\u043e\u043b, \u0440\u0438\u0441\u043f\u0435\u0440\u0438\u0434\u043e\u043d \u0438 \u0434\u0440.), \u0431\u0435\u0442\u0430-\u0431\u043b\u043e\u043a\u0430\u0442\u043e\u0440\u044b (\u043c\u0435\u0442\u043e\u043f\u0440\u043e\u043b\u043e\u043b, \u043f\u0440\u043e\u043f\u0440\u0430\u043d\u043e\u043b\u043e\u043b \u0438 \u0434\u0440.) \u0438\u043b\u0438 \u0442\u0430\u043c\u043e\u043a\u0441\u0438\u0444\u0435\u043d, \u0430 \u0442\u0430\u043a\u0436\u0435 \u043c\u043d\u043e\u0433\u0438\u0435 \u0434\u0440\u0443\u0433\u0438\u0435.<\/p>\n

\u041f\u043e\u043c\u0438\u043c\u043e \u044d\u043a\u0437\u043e\u0433\u0435\u043d\u043d\u044b\u0445 \u0432\u0435\u0449\u0435\u0441\u0442\u0432, \u043e\u043f\u0438\u0441\u0430\u043d\u043d\u044b\u0445 \u0432\u044b\u0448\u0435, CYP2D6 \u0442\u0430\u043a\u0436\u0435 \u0438\u0433\u0440\u0430\u0435\u0442 \u0432\u0430\u0436\u043d\u0443\u044e \u0440\u043e\u043b\u044c \u0432 \u043c\u0435\u0442\u0430\u0431\u043e\u043b\u0438\u0437\u043c\u0435 \u044d\u043d\u0434\u043e\u0433\u0435\u043d\u043d\u044b\u0445 \u0432\u0435\u0449\u0435\u0441\u0442\u0432, \u0442\u0430\u043a\u0438\u0445 \u043a\u0430\u043a \u0442\u0440\u0438\u043f\u0442\u0430\u043c\u0438\u043d\u044b – \u0441\u0435\u043c\u0435\u0439\u0441\u0442\u0432\u043e \u043c\u043e\u043b\u0435\u043a\u0443\u043b, \u0443\u0447\u0430\u0441\u0442\u0432\u0443\u044e\u0449\u0438\u0445 \u0432 \u0440\u0430\u0437\u043b\u0438\u0447\u043d\u044b\u0445 \u0444\u0443\u043d\u043a\u0446\u0438\u044f\u0445 \u043c\u043e\u0437\u0433\u0430.CYP2D6 \u0442\u0430\u043a\u0436\u0435 \u0438\u0433\u0440\u0430\u0435\u0442 \u0432\u0430\u0436\u043d\u0443\u044e \u0440\u043e\u043b\u044c \u0432 \u043c\u0435\u0442\u0430\u0431\u043e\u043b\u0438\u0437\u043c\u0435 \u044d\u043d\u0434\u043e\u0433\u0435\u043d\u043d\u044b\u0445 \u0432\u0435\u0449\u0435\u0441\u0442\u0432, \u0442\u0430\u043a\u0438\u0445 \u043a\u0430\u043a \u0442\u0440\u0438\u043f\u0442\u0430\u043c\u0438\u043d\u044b, \u0441\u0435\u043c\u0435\u0439\u0441\u0442\u0432\u043e \u043c\u043e\u043b\u0435\u043a\u0443\u043b, \u0443\u0447\u0430\u0441\u0442\u0432\u0443\u044e\u0449\u0438\u0445 \u0432 \u0440\u0430\u0437\u043b\u0438\u0447\u043d\u044b\u0445 \u0444\u0443\u043d\u043a\u0446\u0438\u044f\u0445 \u043c\u043e\u0437\u0433\u0430, \u0442\u0430\u043a\u0438\u0445 \u043a\u0430\u043a \u0432\u043e\u0441\u043f\u0440\u0438\u044f\u0442\u0438\u0435 \u0438 \u043f\u043e\u0437\u043d\u0430\u043d\u0438\u0435, \u043d\u0435\u0439\u0440\u043e\u0441\u0442\u0435\u0440\u043e\u0438\u0434\u044b \u0438 \u0442\u0438\u0440\u0430\u043c\u0438\u043d, \u043a\u043e\u0442\u043e\u0440\u044b\u0439 \u043e\u043d \u0438\u0441\u043f\u043e\u043b\u044c\u0437\u0443\u0435\u0442 \u0432 \u043a\u0430\u0447\u0435\u0441\u0442\u0432\u0435 \u0441\u0443\u0431\u0441\u0442\u0440\u0430\u0442\u0430 \u0434\u043b\u044f \u0441\u0438\u043d\u0442\u0435\u0437\u0430 \u0434\u043e\u0444\u0430\u043c\u0438\u043d\u0430, \u043e\u0434\u043d\u043e\u0433\u043e \u0438\u0437 \u0432\u0430\u0436\u043d\u0435\u0439\u0448\u0438\u0445 \u043d\u0435\u0439\u0440\u043e\u0442\u0440\u0430\u043d\u0441\u043c\u0438\u0442\u0442\u0435\u0440\u043e\u0432.<\/p>\n

\u0412\u0430\u0436\u043d\u043e \u043f\u043e\u043c\u043d\u0438\u0442\u044c, \u0447\u0442\u043e \u043d\u0435\u0437\u0430\u0432\u0438\u0441\u0438\u043c\u043e \u043e\u0442 \u0432\u043b\u0438\u044f\u043d\u0438\u044f \u043d\u0430 \u0430\u043a\u0442\u0438\u0432\u043d\u043e\u0441\u0442\u044c \u0440\u0430\u0437\u043b\u0438\u0447\u043d\u044b\u0445 \u0433\u0435\u043d\u043e\u0442\u0438\u043f\u043e\u0432, \u0441\u0443\u0449\u0435\u0441\u0442\u0432\u0443\u0435\u0442 \u043c\u043d\u043e\u0436\u0435\u0441\u0442\u0432\u043e \u0441\u043e\u0435\u0434\u0438\u043d\u0435\u043d\u0438\u0439, \u043a\u043e\u0442\u043e\u0440\u044b\u0435 \u043c\u043e\u0433\u0443\u0442 \u0432\u044b\u0441\u0442\u0443\u043f\u0430\u0442\u044c \u0432 \u043a\u0430\u0447\u0435\u0441\u0442\u0432\u0435 \u0438\u043d\u0433\u0438\u0431\u0438\u0442\u043e\u0440\u043e\u0432 \u0438\u043b\u0438 \u0438\u043d\u0434\u0443\u043a\u0442\u043e\u0440\u043e\u0432 \u0438 \u0441\u0443\u0449\u0435\u0441\u0442\u0432\u0435\u043d\u043d\u043e \u0432\u043b\u0438\u044f\u0442\u044c \u043d\u0430 \u0438\u0445 \u0444\u0443\u043d\u043a\u0446\u0438\u044e. \u042d\u0442\u043e \u043e\u0441\u043e\u0431\u0435\u043d\u043d\u043e \u0432\u0430\u0436\u043d\u043e \u043f\u0440\u0438 \u043f\u043e\u043b\u0438\u0442\u0435\u0440\u0430\u043f\u0438\u0438, \u043f\u043e\u0441\u043a\u043e\u043b\u044c\u043a\u0443 \u043c\u043e\u0436\u0435\u0442 \u043e\u0431\u0443\u0441\u043b\u043e\u0432\u043b\u0438\u0432\u0430\u0442\u044c \u0442\u0435\u0440\u0430\u043f\u0435\u0432\u0442\u0438\u0447\u0435\u0441\u043a\u0438\u0439 \u044d\u0444\u0444\u0435\u043a\u0442 \u0438 \u043d\u0430\u043b\u0438\u0447\u0438\u0435 \u043f\u043e\u0431\u043e\u0447\u043d\u044b\u0445 \u044d\u0444\u0444\u0435\u043a\u0442\u043e\u0432 \u043f\u0440\u0435\u043f\u0430\u0440\u0430\u0442\u043e\u0432, \u043c\u0435\u0442\u0430\u0431\u043e\u043b\u0438\u0437\u0438\u0440\u0443\u0435\u043c\u044b\u0445 CYP2D6.<\/p>","protected":false},"featured_media":0,"comment_status":"closed","ping_status":"closed","template":"","meta":[],"product_brand":[],"product_cat":[968,970],"product_tag":[],"class_list":{"0":"post-9959","1":"product","2":"type-product","3":"status-publish","5":"product_cat-teste-de-biologie-moleculara","6":"product_cat-teste-de-farmacogenetica","8":"first","9":"instock","10":"sold-individually","11":"shipping-taxable","12":"purchasable","13":"product-type-simple"},"_links":{"self":[{"href":"https:\/\/old.synevo.md\/ru\/wp-json\/wp\/v2\/product\/9959","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/old.synevo.md\/ru\/wp-json\/wp\/v2\/product"}],"about":[{"href":"https:\/\/old.synevo.md\/ru\/wp-json\/wp\/v2\/types\/product"}],"replies":[{"embeddable":true,"href":"https:\/\/old.synevo.md\/ru\/wp-json\/wp\/v2\/comments?post=9959"}],"wp:attachment":[{"href":"https:\/\/old.synevo.md\/ru\/wp-json\/wp\/v2\/media?parent=9959"}],"wp:term":[{"taxonomy":"product_brand","embeddable":true,"href":"https:\/\/old.synevo.md\/ru\/wp-json\/wp\/v2\/product_brand?post=9959"},{"taxonomy":"product_cat","embeddable":true,"href":"https:\/\/old.synevo.md\/ru\/wp-json\/wp\/v2\/product_cat?post=9959"},{"taxonomy":"product_tag","embeddable":true,"href":"https:\/\/old.synevo.md\/ru\/wp-json\/wp\/v2\/product_tag?post=9959"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}