{"id":10320,"date":"2020-04-23T05:02:55","date_gmt":"2020-04-23T02:02:55","guid":{"rendered":"https:\/\/www.synevo.ro\/product\/fenitoin\/"},"modified":"2025-02-10T15:37:49","modified_gmt":"2025-02-10T13:37:49","slug":"fenitoin","status":"publish","type":"product","link":"https:\/\/old.synevo.md\/ru\/shop\/fenitoin\/","title":{"rendered":"\u0424\u0435\u043d\u0438\u0442\u043e\u0438\u043d"},"content":{"rendered":"

Informa\u0163ii generale \u015fi recomand\u0103ri pentru testare<\/em><\/strong><\/span><\/p>\n

In practica medical\u0103 curent\u0103 este recunoscut\u0103 din ce \u00een ce mai mult importan\u0163a determin\u0103rii periodice a nivelului \u00een s\u00e2nge al multora din medicamentele administrate, fie datorit\u0103 poten\u0163ialului crescut de reac\u0163ii adverse, fie complian\u0163ei reduse a pacien\u0163ilor.<\/span><\/p>\n

Monitorizarea terapeutic\u0103 a unui medicament (Therapeutic Drug Monitoring, TDM) are drept scop men\u0163inerea concentra\u0163iei acestuia \u00een intervalul terapeutic<\/strong>, definit ca acel interval de valori ale nivelului \u00een ser, plasm\u0103 sau s\u00e2nge integral \u00een care medicamentul respectiv \u00eesi exercit\u0103 efectele clinice cu reac\u0163ii adverse minime pentru majoritatea pacien\u0163ilor.<\/span><\/p>\n

Conceptul de TDM se refer\u0103 astfel la m\u0103surarea concentra\u0163iei medicamentelor pentru a optimiza si adapta tratamentul la nivel individual (terapie personalizat\u0103). Pentru realizarea acestei \u0163inte terapeutice este important s\u0103 se cunoasc\u0103 pentru medicamentele administrate date legate de:<\/span><\/p>\n

-farmacocinetic\u0103<\/span>: studiaz\u0103 efectele medicamentului asupra organismului (rela\u0163ia doz\u0103-efect);<\/span><\/p>\n

-farmacodinamic\u0103<\/span>: studiaz\u0103 efectele organismului asupra medicamentelor (absorb\u0163ie, distribu\u0163ie etc);\u00a0<\/em><\/strong><\/span><\/p>\n

-farmacogenetic\u0103<\/span>: studiaz\u0103 modelul genetic al metaboliz\u0103rii medicamentelor lu\u00e2nd \u00een considerare varia\u0163iile individuale.\u00a0<\/em><\/strong><\/span><\/p>\n

Pentru a ob\u0163ine rezultate pentru concentra\u0163iile medicamentoase cu utilitate clinic\u0103 este important ca proba s\u0103 fie recoltat\u0103 \u00een asa numita \u201esteady state\u201d<\/strong> (stare de echilibru) \u00een care rata de medicament ce p\u0103trunde \u00een organism este egal\u0103 cu cea eliminat\u0103. Atunci c\u00e2nd o doz\u0103 fix\u0103 de medicament este administrat\u0103 la intervale de timp regulate, acesta se va acumula \u00een organism \u00een cursul fazei de absorb\u0163ie p\u00e2n\u0103 este atins\u0103 starea de echilibru; perioada de timp necesar\u0103 pentru a se ajunge la steady state<\/em> depinde de\u00a0 timpul de \u00eenjum\u0103t\u0103\u0163ire al medicamentului (T1\/2<\/sub>)<\/strong>, adic\u0103 timpul \u00een care concentra\u0163ia medicamentului \u00een s\u00e2nge se reduce la jum\u0103tate. La r\u00e2ndul s\u0103u T1\/2 <\/sub>depinde de rata de metabolizare si excre\u0163ie. In condi\u0163iile unei distribu\u0163ii rapide si uniforme a medicamentului \u00een organism (cinetic\u0103 de ordinul I), precum si\u00a0\u00een absen\u0163a unei doze de \u00eenc\u0103rcare, este nevoie de un interval de timp echivalent cu cel pu\u0163in 5 T1\/2<\/sub>\u00a0 pentru a ob\u0163ine steady state<\/em> (vezi fig. 20.3.1<\/em>)1;2;4<\/sup>.<\/span>\u00a0\"-\"<\/a><\/span><\/p>\n

\"-\"<\/a><\/p>\n

Fig 20.3.1 Ob\u0163inerea\u00a0\u201e<\/strong>steady state\u201d<\/strong><\/p>\n

Acest proces poate fi rezumat astfel:<\/span><\/p>\n

k\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0k = constanta de dispari\u0163ie a lui D<\/span><\/span><\/p>\n

D\u2192E\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0 D = concentra\u0163ia medicamentului\u00a0 E = forma excretat\u0103 a medicamentului<\/span><\/p>\n

\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0 <\/span>\u04231\/2<\/sub> = 0.693\/k<\/span><\/p>\n

Asa cum reiese din ecua\u0163ie, T1\/2 <\/sub>este o constant\u0103 si nu depinde de concentra\u0163ia medicamentului. Dac\u0103 T1\/2 <\/sub>este cunoscut se poate calcula modul de \u00eemp\u0103r\u0163ire a dozelor si intervalul de timp la care trebuie administrate pentru a se atinge nivelul terapeutic.<\/span><\/p>\n

Totusi, unele medicamente sunt metabolizate printr-un alt tip de cinetic\u0103 dec\u00e2t cea de ordinul I, suferind mai \u00eent\u00e2i o metabolizare\u00a0\u00een ficat, urmat\u0103 de o distribu\u0163ie multicompartimental\u0103\u00a0\u00een organism (medicamentul are o anumit\u0103 rat\u0103 de distribu\u0163ie plasmatic\u0103\u00a0 si o rata diferit\u0103 de distribu\u0163ie tisular\u0103). In aceste cazuri timpul necesar pentru a atinge steady state <\/em>poate s\u0103 fie diferit de echivalentul a 5 T1\/2<\/sub> .<\/span><\/p>\n

Cu excep\u0163ia urgen\u0163elor medicale, \u00een cazurile\u00a0\u00een care se modific\u0103 dozele administrate si se adaug\u0103 sau se scot medicamente asociate, se va astepta ob\u0163inerea unei noi st\u0103ri de echilibru \u00eenainte de recoltarea probei pentru monitorizarea terapeutic\u0103. Intr-un mod similar, se va astepta aceeasi perioad\u0103 de timp p\u00e2n\u0103 c\u00e2nd un medicament aflat\u00a0\u00een steady state <\/em>se va elimina din organism la \u00eentreruperea administr\u0103rii2<\/sup>.<\/span><\/p>\n

Odat\u0103 atins\u0103 starea de echilibru probele de s\u00e2nge pot fi recoltate \u00een dou\u0103 momente diferite:<\/span><\/p>\n

\u2013 \u00een momentul nivelului maxim (peak samples<\/em>): la 2-3 ore dup\u0103 administrarea unei doze orale, la 30-60 minute dup\u0103 o doza administrat\u0103 intravenos, la 2-4 ore dup\u0103 o doza administrat\u0103 intramuscular sau la 1-1 si \u00bd ore dup\u0103 o doz\u0103 administrat\u0103 intranazal;<\/span><\/p>\n

\u2013 \u00een momentul nivelului minim (trough samples<\/em>): imediat \u00eenaintea administr\u0103rii urm\u0103toarei doze; acest moment este recomandat \u00een majoritatea cazurilor.<\/span><\/p>\n

Monitorizarea terapeutic\u0103 a medicamentelor este indicat\u0103 \u00een special \u00een urm\u0103toarele situa\u0163ii:<\/span><\/p>\n

\u2022 perturbarea rela\u0163iei doz\u0103-efect;<\/span><\/div>\n
\u2022 esec \u00een ob\u0163inerea efectului terapeutic sau suspectarea unei intoxica\u0163ii;<\/span><\/div>\n
\u2022 efect imposibil sau foarte greu de confirmat clinic (de exemplu \u00een cazul imunosupresoarelor);<\/span><\/div>\n
\u2022 interval terapeutic \u00eengust (de exemplu \u00een cazul glicozidelor);<\/span><\/div>\n
\u2022 complian\u0163a redus\u0103 a pacien\u0163ilor (persoane v\u00e2rstnice sau cu boli psihice);<\/span><\/div>\n
\u2022 prezen\u0163a unor afec\u0163iuni care afecteaz\u0103 absorb\u0163ia, distribu\u0163ia, metabolizarea si excre\u0163ia medicamentelor;<\/span><\/div>\n
\u2022 administrarea simultan\u0103 de medicamente care prezint\u0103 aceeasi cale de eliminare;<\/span><\/div>\n
\u2022 copii si persoane v\u00e2rstnice la care este afectat volumul de distribu\u0163ie: redus \u00een cazul v\u00e2rstnicilor si crescut la copii.<\/span><\/div>\n

Clasele de medicamente pentru care se recomand\u0103 \u00een mod special TDM sunt urm\u0103toarele:<\/span><\/p>\n

    \n
  • glicozide cardiace: digoxin, digitoxin;<\/span><\/li>\n
  • antiaritmice:\u00a0 amiodarona, flecainida, procainamida, chinidina;<\/span><\/li>\n
  • antiastmatice: teofilina;<\/span><\/li>\n
  • antibiotice: aminoglicozide, vancomicina;<\/span><\/li>\n
  • antivirale: medicamentele pentru infec\u0163ia HIV, ganciclovir;<\/span><\/li>\n
  • anticonvulsivante: fenobarbital, carbamazepin, fenitoin, acid valproic, gabapentin, primidona, lamotrigin;<\/span><\/li>\n
  • medicamente psihotrope: litiu, antidepresive triciclice, neuroleptice;<\/span><\/li>\n
  • imunosupresoare: ciclosporina, tacrolimus, sirolimus, everolimus, acid micofenolic, azatioprina;<\/span><\/li>\n
  • citostatice: methotrexat1;2<\/sup>.<\/span><\/li>\n<\/ul>\n

    In tabelul de mai jos sunt precizate pentru anumite medicamente T1\/2<\/sub>, intervalul de timp necesar pentru a se ajunge la steady state<\/em>, tipul de prob\u0103 pentru TDM si stabilitatea acesteia, intervalul terapeutic1;4<\/sup>:<\/span><\/p>\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n
    \n

    MEDICAMENT<\/strong><\/span><\/p>\n<\/td>\n

    		\n

    \u04231\/2<\/sub><\/strong>\u00a0<\/strong><\/span><\/p>\n<\/td>\n

    		\n

    T p\u00e2n\u0103 la steady state<\/strong><\/span><\/p>\n<\/td>\n

    		\n

    Tip prob\u0103<\/strong><\/span><\/p>\n<\/td>\n

    		\n

    Stabilitate prob\u0103<\/strong><\/span><\/p>\n<\/td>\n

    		\n

    Metoda de determinare<\/strong><\/span><\/p>\n<\/td>\n

    		\n

    Interval terapeutic<\/strong><\/span><\/p>\n<\/td>\n<\/tr>\n

    \n

    \u0414\u0438\u0433\u043e\u043a\u0441\u0438\u043d<\/span><\/p>\n<\/td>\n

    		\n

    36-48 h<\/span><\/p>\n<\/td>\n

    		\n

    7-10 zile<\/span><\/p>\n<\/td>\n

    		\n

    \u0421\u044b\u0432\u043e\u0440\u043e\u0442\u043a\u0430<\/span><\/p>\n<\/td>\n

    		7 zile la 2-8\u00b0C<\/span><\/td>\n\n

    ECLIA<\/span><\/p>\n<\/td>\n

    		0.9-2 ng\/mL<\/span><\/td>\n<\/tr>\n
    \n

    Amiodarona<\/span><\/p>\n<\/td>\n

    		\n

    26-107 zile<\/span><\/p>\n<\/td>\n

    		Nu se aplic\u0103<\/span><\/td>\n\u0421\u044b\u0432\u043e\u0440\u043e\u0442\u043a\u0430<\/span><\/td>\n\n

    7 zile <\/span>la 2-8\u00b0C<\/span><\/p>\n<\/td>\n

    		\n

    HPLC<\/span><\/p>\n<\/td>\n

    		\n

    0.5-2 mg\/L<\/span><\/p>\n<\/td>\n<\/tr>\n

    Flecainida<\/span><\/td>\n\n

    12-27 ore<\/span><\/p>\n<\/td>\n

    		\n

    3-6 zile<\/span><\/p>\n<\/td>\n

    		\n

    \u0421\u044b\u0432\u043e\u0440\u043e\u0442\u043a\u0430<\/span><\/p>\n<\/td>\n

    		\n

    7 zile <\/span>la 2-8\u00b0C<\/span><\/p>\n<\/td>\n

    		\n

    HPLC<\/span><\/p>\n<\/td>\n

    		\n

    0.2-0.8 mg\/L<\/span><\/p>\n<\/td>\n<\/tr>\n

    Teofilina<\/span><\/td>\n\n

    7-11 ore (adult)<\/span><\/p>\n

    \u00a01-8 ore (copil)<\/span><\/p>\n<\/td>\n

    		15-55 ore (adult);<\/span><\/p>\n

    5-40 ore (copil)<\/span><\/td>\n

    		\n

    \u0421\u044b\u0432\u043e\u0440\u043e\u0442\u043a\u0430<\/span><\/p>\n<\/td>\n

    		\n

    7 zile <\/span>la 2-8\u00b0C<\/span><\/p>\n<\/td>\n

    		\n

    HPLC<\/span><\/p>\n<\/td>\n

    		\n
    < 1 an:<\/span><\/div>\n
    5-10 mg\/L<\/span><\/div>\n
    <\/div>\n
    \u00a0\u00a0\u00a0\u00a0\u00a0\u2265 1 an:\u00a0\u00a0\u00a0<\/span><\/div>\n
    8-20 mg\/L<\/span><\/div>\n<\/td>\n<\/tr>\n
    \u0412\u0430\u043d\u043a\u043e\u043c\u0438\u0446\u0438\u043d<\/span><\/td>\n\n

    3-8 ore<\/span><\/p>\n<\/td>\n

    		\n

    1-2 zile<\/span><\/p>\n<\/td>\n

    		\n

    \u0421\u044b\u0432\u043e\u0440\u043e\u0442\u043a\u0430<\/span><\/p>\n<\/td>\n

    		\n

    7 zile <\/span>la 2-8\u00b0C<\/span><\/p>\n<\/td>\n

    		\n

    FPIA<\/span><\/p>\n<\/td>\n

    		\n

    5 \u2013 10 \u00b5g\/mL<\/span><\/p>\n

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

    \n

    Carbamazepin<\/span><\/p>\n<\/td>\n

    		\n

    14-47 ore (adult)<\/span><\/p>\n

    8-19 ore (copil)<\/span><\/p>\n<\/td>\n

    		\n

    7-12 zile (adult);<\/span><\/p>\n

    2-4 zile (copil)<\/span><\/p>\n<\/td>\n

    		\n

    \u0421\u044b\u0432\u043e\u0440\u043e\u0442\u043a\u0430<\/span><\/p>\n<\/td>\n

    		\n

    7 zile <\/span>la 2-8\u00b0C<\/span><\/p>\n<\/td>\n

    		\n

    HPLC<\/span><\/p>\n<\/td>\n

    		\n

    4-10 mg\/L<\/span><\/p>\n<\/td>\n<\/tr>\n

    \n

    \u0412\u0430\u043b\u044c\u043f\u0440\u043e\u0435\u0432\u0430\u044f \u043a\u0438\u0441\u043b\u043e\u0442\u0430<\/a><\/span><\/p>\n<\/td>\n

    		\n

    9-16 ore (adult)<\/span><\/p>\n

    7-13 ore (copil)<\/span><\/p>\n<\/td>\n

    		\n

    2-4 zile (adult)<\/span><\/p>\n

    2-4 zile (copil)<\/span><\/p>\n<\/td>\n

    		\u0421\u044b\u0432\u043e\u0440\u043e\u0442\u043a\u0430<\/span><\/td>\n7 zile la 2-8\u00b0C<\/span><\/td>\nCEDIA<\/span><\/td>\n50-100 mg\/L<\/span><\/td>\n<\/tr>\n
    \n

    \u0422\u043e\u043f\u0438\u0440\u0430\u043c\u0430\u0442<\/span><\/p>\n<\/td>\n

    		\n

    19-23 ore<\/span><\/p>\n<\/td>\n

    		\n

    5 zile<\/span><\/p>\n<\/td>\n

    		\n

    \u0421\u044b\u0432\u043e\u0440\u043e\u0442\u043a\u0430<\/span><\/p>\n<\/td>\n

    		\n

    7 zile <\/span>la 2-8\u00b0C<\/span><\/p>\n<\/td>\n

    		\n

    HPLC<\/span><\/p>\n<\/td>\n

    		\n

    1-10 mg\/L<\/span><\/p>\n<\/td>\n<\/tr>\n

    \n

    Etosuximid<\/span><\/p>\n<\/td>\n

    		\n

    50-60 ore (adult)<\/span><\/p>\n

    30 ore (copil)<\/span><\/p>\n<\/td>\n

    		\n

    8-12 zile (adult)<\/span><\/p>\n

    6-10 zile (copil)<\/span><\/p>\n<\/td>\n

    		\n

    \u0421\u044b\u0432\u043e\u0440\u043e\u0442\u043a\u0430<\/span><\/p>\n<\/td>\n

    		\n

    7 zile <\/span>la 2-8\u00b0C<\/span><\/p>\n<\/td>\n

    		\n

    HPLC<\/span><\/p>\n<\/td>\n

    		\n

    40-100 mg\/L<\/span><\/p>\n<\/td>\n<\/tr>\n

    \n

    \u0424\u0435\u043d\u043e\u0431\u0430\u0440\u0431\u0438\u0442\u0430\u043b<\/a><\/span><\/p>\n<\/td>\n

    		\n

    81-117 ore (adult)<\/span><\/p>\n

    40-70 ore (copil)<\/span><\/p>\n<\/td>\n

    		\n

    17-24 zile (adult)<\/span><\/p>\n

    8-15 zile (copil)<\/span><\/p>\n<\/td>\n

    		\n

    \u0421\u044b\u0432\u043e\u0440\u043e\u0442\u043a\u0430<\/span><\/p>\n<\/td>\n

    		\n

    7 zile <\/span>la 2-8\u00b0C<\/span><\/p>\n<\/td>\n

    		\n

    HPLC<\/span><\/p>\n<\/td>\n

    		\n

    10-40 mg\/L<\/span><\/p>\n<\/td>\n<\/tr>\n

    \n

    \u0424\u0435\u043d\u0438\u0442\u043e\u0438\u043d<\/strong><\/span><\/p>\n<\/td>\n

    		\n

    18-22 ore (adult)<\/strong><\/span>7-29 ore (copil)<\/strong><\/span><\/p>\n<\/td>\n

    		\n

    4-8 zile (adult)<\/strong><\/span><\/p>\n

    2-5 zile (copil)<\/strong><\/span><\/p>\n<\/td>\n

    		\n

    \u0421\u044b\u0432\u043e\u0440\u043e\u0442\u043a\u0430<\/strong><\/span><\/p>\n<\/td>\n

    		\n

    7 zile <\/strong><\/span>la 2-8\u00b0C<\/strong><\/span><\/p>\n<\/td>\n

    		HPLC<\/strong><\/span><\/td>\n\n
    <14 ani:<\/strong><\/span><\/div>\n
    10-20 mg\/L<\/strong><\/span><\/div>\n
    <\/div>\n
    >14 ani:<\/strong><\/span><\/div>\n
    6-14 mg\/L<\/strong><\/span><\/div>\n<\/td>\n<\/tr>\n
    \n

    \u0413\u0430\u0431\u0430\u043f\u0435\u043d\u0442\u0438\u043d<\/span><\/p>\n<\/td>\n

    		\n

    5-7 ore (adult)<\/span><\/p>\n

    4-6 ore (copil)<\/span><\/p>\n<\/td>\n

    		\n

    1-2 zile (adult)<\/span><\/p>\n

    1-2 zile (copil)<\/span><\/p>\n<\/td>\n

    		\u0421\u044b\u0432\u043e\u0440\u043e\u0442\u043a\u0430<\/span><\/td>\n7 zile la 2-8\u00b0C<\/span><\/td>\nHPLC<\/span><\/td>\n2 \u2013 10 \u00b5g\/mL<\/span><\/td>\n<\/tr>\n
    \u041b\u0430\u043c\u043e\u0442\u0440\u0438\u0434\u0436\u0438\u043d<\/span><\/td>\n\n

    15-30 ore (adult)<\/span><\/p>\n

    30 ore (copil)<\/span><\/p>\n<\/td>\n

    		3-10 zile (adult)<\/span><\/p>\n

    3-10 zile (copil)<\/span><\/td>\n

    		\u0421\u044b\u0432\u043e\u0440\u043e\u0442\u043a\u0430<\/span><\/td>\n7 zile\u00a0la 2-8\u00b0C<\/span><\/td>\nHPLC<\/span><\/td>\n\n
    <14 ani:<\/span><\/div>\n
    5-15 mg\/L<\/span><\/div>\n
    <\/div>\n
    >14 ani:<\/span><\/div>\n
    1-5 mg\/L<\/span><\/div>\n<\/td>\n<\/tr>\n
    \n

    \u041f\u0440\u0438\u043c\u0438\u0434\u043e\u043d<\/span><\/p>\n<\/td>\n

    		\n

    3-7 ore (adult)<\/span><\/p>\n

    4-6 ore (copil)<\/span><\/p>\n<\/td>\n

    		\n

    16-60 ore (adult)<\/span><\/p>\n

    20-30 ore (copil)<\/span><\/p>\n<\/td>\n

    		\n

    \u0421\u044b\u0432\u043e\u0440\u043e\u0442\u043a\u0430<\/span><\/p>\n<\/td>\n

    		\n

    7 zile <\/span>la 2-8\u00b0C<\/span><\/p>\n<\/td>\n

    		HPLC<\/span><\/td>\n\n

    5-15 mg\/L<\/span><\/p>\n<\/td>\n<\/tr>\n

    \n

    Amitriptilina<\/span><\/p>\n<\/td>\n

    		\n

    8-51 ore<\/span><\/p>\n<\/td>\n

    		2-6 zile<\/span><\/td>\n\u0421\u044b\u0432\u043e\u0440\u043e\u0442\u043a\u0430<\/span><\/td>\n\n

    7 zile la 2-8\u00b0C<\/span><\/p>\n<\/td>\n

    		LC-MS\/MS<\/span><\/td>\n50-300 \u00b5g\/L<\/span><\/td>\n<\/tr>\n
    \n

    \u041b\u0438\u0442\u0438\u0439<\/span><\/p>\n<\/td>\n

    		\n

    14-30 ore<\/span><\/p>\n<\/td>\n

    		\n

    2-7 zile<\/span><\/p>\n<\/td>\n

    		\n

    \u0421\u044b\u0432\u043e\u0440\u043e\u0442\u043a\u0430<\/span><\/p>\n<\/td>\n

    		\n

    8 ore<\/em> la temperatura camerei<\/span><\/p>\n

    24 ore<\/em> la 2-8\u00b0C <\/span><\/p>\n

    6 luni<\/em> la -18\u00b0C<\/span><\/p>\n<\/td>\n

    		\n

    ISE<\/span><\/p>\n<\/td>\n

    		\n

    Mania acut\u0103: 0.6-1.2 mmol\/L.<\/span><\/p>\n

    \u2022 Protec\u0163ie \u00eempotriva viitoarelor episoade la pacien\u0163ii cu afec\u0163iune bipolar\u0103: <\/span><\/div>\n
    0.8-1.0 mmol\/L<\/span><\/div>\n

    \u2022 Depresie: 0.5- 1.5 mmol\/L<\/span><\/p>\n<\/td>\n<\/tr>\n

    \n

    Clomipramin<\/span><\/p>\n<\/td>\n

    		\n

    12-36 ore<\/span><\/p>\n<\/td>\n

    		3 s\u0103pt\u0103m\u00e2ni<\/span><\/td>\n\u0421\u044b\u0432\u043e\u0440\u043e\u0442\u043a\u0430<\/span><\/td>\n\n

    7 zile <\/span>la 2-8\u00b0C<\/span><\/p>\n<\/td>\n

    		\n

    LC-MS\/MS<\/span><\/p>\n<\/td>\n

    		\n

    90-250 \u00b5g\/L<\/span><\/p>\n<\/td>\n<\/tr>\n

    \n

    Clozapina<\/span><\/p>\n<\/td>\n

    		4-66 ore<\/span><\/td>\nNu se aplic\u0103<\/span><\/td>\n\n

    \u0421\u044b\u0432\u043e\u0440\u043e\u0442\u043a\u0430<\/span><\/p>\n<\/td>\n

    		\n

    7 zile <\/span>la 2-8\u00b0C<\/span><\/p>\n<\/td>\n

    		LC-MS\/MS<\/span><\/td>\n\n

    350-600 \u00b5g\/L<\/span><\/p>\n<\/td>\n<\/tr>\n

    \n

    Olanzapin<\/span><\/p>\n<\/td>\n

    		\n

    21-54 ore (adult \u226465 ani)<\/span><\/p>\n

    32-81 ore (adult >65 ani)<\/span><\/p>\n<\/td>\n

    		\n

    7 zile<\/span><\/p>\n<\/td>\n

    		\n

    \u0421\u044b\u0432\u043e\u0440\u043e\u0442\u043a\u0430<\/span><\/p>\n<\/td>\n

    		7 zile\u00a0<\/span>la 2-8\u00b0C<\/span><\/td>\nLC-MS\/MS<\/span><\/td>\n\u00a010-80 \u00b5g\/L<\/span><\/td>\n<\/tr>\n
    \n

    Doxepin<\/span><\/p>\n<\/td>\n

    		\n

    8-25 ore<\/span><\/p>\n<\/td>\n

    		\n

    2.5-5 zile<\/span><\/p>\n<\/td>\n

    		\n

    \u0421\u044b\u0432\u043e\u0440\u043e\u0442\u043a\u0430<\/span><\/p>\n<\/td>\n

    		\n

    7 zile <\/span>la 2-8\u00b0C<\/span><\/p>\n<\/td>\n

    		\n

    LC-MS\/MS<\/span><\/p>\n<\/td>\n

    		\n

    20-150 \u00b5g\/L<\/span><\/p>\n<\/td>\n<\/tr>\n

    \n

    Imipramin<\/span><\/p>\n<\/td>\n

    		\n

    6-20 ore<\/span><\/p>\n<\/td>\n

    		\n

    2-5 zile<\/span><\/p>\n<\/td>\n

    		\u0421\u044b\u0432\u043e\u0440\u043e\u0442\u043a\u0430<\/span><\/td>\n\n

    7 zile <\/span>la 2-8\u00b0C<\/span><\/p>\n<\/td>\n

    		LC-MS\/MS<\/span><\/td>\n45-150 \u00b5g\/L<\/span><\/td>\n<\/tr>\n
    \n

    Maprotilin<\/span><\/p>\n<\/td>\n

    		\n

    36-105 ore<\/span><\/p>\n<\/td>\n

    		14 zile<\/span><\/td>\n\n

    \u0421\u044b\u0432\u043e\u0440\u043e\u0442\u043a\u0430<\/span><\/p>\n<\/td>\n

    		7 zile la 2-8\u00b0C<\/span><\/td>\nLC-MS\/MS<\/span><\/td>\n125-200 \u00b5g\/L<\/span><\/td>\n<\/tr>\n
    \n

    Trimipramin<\/span><\/p>\n<\/td>\n

    		\n

    16-39 ore<\/span><\/p>\n<\/td>\n

    		\n

    Nu se aplic\u0103<\/span><\/p>\n<\/td>\n

    		\n

    \u0421\u044b\u0432\u043e\u0440\u043e\u0442\u043a\u0430<\/span><\/p>\n<\/td>\n

    		\n

    7 zile <\/span>la 2-8\u00b0C<\/span><\/p>\n<\/td>\n

    		\n

    LC-MS\/MS<\/span><\/p>\n<\/td>\n

    		\n

    150-350 \u00b5g\/L<\/span><\/p>\n<\/td>\n<\/tr>\n

    Haloperidol<\/span><\/td>\n\n

    41-41 ore (lactat)<\/span><\/p>\n

    14-28 zile (decanoat)<\/span><\/span><\/p>\n<\/td>\n

    		\n

    3-9 zile (lactat)<\/span><\/p>\n

    nu se aplic\u0103<\/span><\/p>\n<\/td>\n

    		\n

    \u0421\u044b\u0432\u043e\u0440\u043e\u0442\u043a\u0430<\/span><\/p>\n<\/td>\n

    		7 zile\u00a0la 2-8\u00b0C<\/span><\/td>\nLC-MS\/MS<\/span><\/td>\n5-16 \u00b5g\/L<\/span><\/td>\n<\/tr>\n
    \n

    Risperidon<\/span><\/p>\n<\/td>\n

    		\n

    3 ore (fast metabolizer risperidon); 21 ore (fast metabolizer9-hidroxi-risperidon); 20 ore (slow metabolizer risperidon); 30 ore (slow metabolizer 9-hidroxi-risperidon);<\/span><\/p>\n<\/td>\n

    		\n

    1 zi (fast metabolizer risperidon); 5-6 zile\u00a0 (fast metabolizer9-hidroxi-risperidon); 5 zile (slow metabolizer risperidon); nu se aplica (slow metabolizer 9-hidroxi-risperidon).<\/span><\/p>\n<\/td>\n

    		\n

    \u0421\u044b\u0432\u043e\u0440\u043e\u0442\u043a\u0430<\/span><\/p>\n<\/td>\n

    		\n

    7 zile <\/span>la 2-8\u00b0C<\/span><\/p>\n<\/td>\n

    		\n

    LC-MS\/MS<\/span><\/p>\n<\/td>\n

    		\n

    10-120 \u00b5g\/L<\/span><\/p>\n<\/td>\n<\/tr>\n

    \n

    Ciclosporina A<\/span><\/p>\n<\/td>\n

    		\n

    6-27 ore<\/span><\/p>\n<\/td>\n

    		\n

    2-6 zile<\/span><\/p>\n<\/td>\n

    		\n

    S\u00e2nge EDTA<\/span><\/p>\n<\/td>\n

    		\n

    5 zile <\/span>la -20\u00b0C<\/span><\/p>\n<\/td>\n

    		\n

    LC-MS\/MS<\/span><\/p>\n<\/td>\n

    		\n

    Intervalul terapeutic variaz\u0103 \u00een func\u0163ie de tipul transplantului si perioada de timp de la transplant<\/span><\/p>\n

    Pentru afec\u0163iuni dermatologice \u015fi reumatologice:<100 \u00b5g\/L<\/span><\/p>\n

    Pentru sindrom nefrotic: <\/span><\/div>\n
    60-160 \u00b5g\/L<\/span><\/div>\n<\/td>\n<\/tr>\n
    \n

    Tacrolimus<\/span><\/p>\n<\/td>\n

    		\n

    4-35 ore (adult)<\/span><\/p>\n

    4-12 ore (copil)<\/span><\/p>\n<\/td>\n

    		\n

    2-6 zile (adult)<\/span>\u00a0<\/span><\/p>\n

    nu se aplic\u0103 la copil<\/span><\/p>\n<\/td>\n

    		\n

    S\u00e2nge EDTA<\/span><\/p>\n<\/td>\n

    		5 zile la -20\u00b0C<\/span><\/td>\n\n

    LC-MS\/MS<\/span><\/p>\n<\/td>\n

    		\n
    \u2013 \u00een primele 2 luni de la transplant:<\/span><\/div>\n
    15-20 \u00b5g\/L<\/span><\/div>\n
    <\/div>\n
    \u2013 dup\u0103 2 luni de la transplant:<\/span><\/div>\n
    8-15 \u00b5g\/L<\/span><\/div>\n<\/td>\n<\/tr>\n
    \u0421\u0438\u0440\u043e\u043b\u0438\u043c\u0443\u0441 \u0432 \u043a\u0440\u043e\u0432\u0438<\/span><\/td>\n\n

    46-78 ore<\/span><\/p>\n<\/td>\n

    		5-7 zile<\/span><\/td>\nS\u00e2nge EDTA<\/span><\/td>\n5 zile la -20\u00b0C<\/span><\/td>\nLC-MS\/MS<\/span><\/td>\n4-20 \u00b5g\/L<\/span><\/td>\n<\/tr>\n
    \n

    Acid micofenolic<\/span><\/p>\n<\/td>\n

    		\n

    8-18 ore (adult)<\/span>variabil la copil<\/span><\/p>\n<\/td>\n

    		\n

    Nu se aplic\u0103<\/span><\/p>\n<\/td>\n

    		\n

    \u0421\u044b\u0432\u043e\u0440\u043e\u0442\u043a\u0430<\/span><\/p>\n<\/td>\n

    		7 zile la 2-8\u00b0C<\/span><\/td>\n\n

    HPLC<\/span><\/p>\n<\/td>\n

    		1-3.5 \u00b5g\/mL<\/span><\/td>\n<\/tr>\n
    \n

    Methotrexat<\/span><\/p>\n<\/td>\n

    		\n

    Cinetic\u0103 bifazic\u0103<\/span><\/p>\n<\/td>\n

    		-<\/span><\/td>\n\n

    \u0421\u044b\u0432\u043e\u0440\u043e\u0442\u043a\u0430<\/span><\/p>\n

    \u00a0<\/span><\/td>\n

    		7 zile la 2-8\u00b0C protejat de lumin\u0103<\/span><\/td>\nFPIA<\/span><\/td>\nSe asociaz\u0103 cu un risc crescut de toxicitate:<\/span><\/p>\n

    \u2013 valorile > 5-10\u00a0 \u00b5mol\/L la 24 h de la admistrare;<\/span><\/p>\n

    \u2013 valorile > 0.5-1\u00a0 \u00b5mol\/L la 48 h de la administrare;<\/span><\/p>\n

    \u2013 valorile > 0.2\u00a0 \u00b5mol\/L la 72 h de la administrare<\/span><\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

    ECLIA = metod\u0103 imunochimic\u0103 cu detec\u0163ie prin chemiluminiscent\u0103<\/span><\/p>\n

    HPLC = cromatografie de lichide sub \u00eenalt\u0103 presiune<\/span><\/p>\n

    LC-MS\/MS = cromatografie de lichide cuplat\u0103 cu spectrometrie de mas\u0103<\/span><\/p>\n

    FPIA = fluorescent polarization immunoassay (metod\u0103 imunochimic\u0103 cu detec\u0163ie prin fluorescen\u0163\u0103 polarizat\u0103)<\/span><\/p>\n

    CEDIA = cloned enzyme donor immunoassay (metod\u0103 imunoenzimatic\u0103 care utilizeaz\u0103 tehnologia ADN-ului recombinant)<\/span><\/p>\n

    ISE = ion selective electrode (metod\u0103 poten\u0163iometric\u0103)<\/span><\/p>\n

    Anticonvulsivante<\/span><\/strong><\/span><\/p>\n

    Sunt medicamente utile \u00een tratamentul epilepsiei,\u00a0\u00een special pentru crizele grand mal<\/em>, petit mal<\/em>, psihomotorii, precum \u015fi \u00een unele afec\u0163iuni cum ar fi tic douloureux<\/em> (nevralgia de trigemen). De\u015fi mecanismul de ac\u0163iune al acestor medicamente nu a fost elucidat, se pare c\u0103 toate, posibil cu excep\u0163ia fenobarbitalului, blocheaz\u0103 influxul de sodiu \u00een neuronii a c\u0103ror membran\u0103 este afectat\u0103. In plus, unele medicamente \u015fi \u00een special fenitoinul blocheaz\u0103 de asemenea influxul secundar de calciu \u00een aceste celule. Fenobarbitalul \u015fi, posibil, fenitoinul stabilizeaz\u0103 membrana neuronilor afecta\u0163i.<\/span><\/p>\n

    Multe din anticonvulsivante exercit\u0103 efect asupra convulsiilor grand mal<\/em>, \u00eens\u0103 sunt ineficace asupra celor de tip petit mal<\/em>. Doar etosuximidul \u015fi acidul valproic au un efect terpeutic \u00een aceste condi\u0163ii.<\/span><\/p>\n

    In concluzie, de\u015fi mecanismul de ac\u0163iune al anticonvulsivantelor pare s\u0103 fie similar, acestea difer\u0103 \u00een ceea ce prive\u015fte specificitatea2<\/sup>.<\/span><\/p>\n

    \u0424\u0435\u043d\u0438\u0442\u043e\u0438\u043d<\/strong><\/span><\/p>\n

    Constituie medicamentul de elec\u0163ie pentru tratamentul \u015fi profilaxia convulsiilor tonico-clonice \u015fi psihomotorii. Dac\u0103 singur nu este eficace se poate asocia cu fenobarbitalul.<\/span><\/p>\n

    Terapia cu fenitoin este ini\u0163iat\u0103 cu doze de 100-300 mg\/zi la adult \u015fi de 4 mg\/kg corp\/zi la copil. Deoarece absorb\u0163ia sa este variabil\u0103 \u015fi medicamentul exprim\u0103 o cinetic\u0103 de ordinul 0 (nelinear\u0103), dozele trebuie ajustate \u00eentr-un interval de 5 zile utilizand concentra\u0163ia seric\u0103 pentru ghidarea terapiei. Biodisponibilitatea orala variaz\u0103 \u00eentre 80% \u015fi 95% fiind dependent\u0103 de diet\u0103.<\/span><\/p>\n

    Fenitoinul prezint\u0103 de asemenea o farmacocinetic\u0103 de ordinul 0, adic\u0103 rata clearance-ului este dependent\u0103 de concentra\u0163ia medicamentului. Astfel, fenitoinul nu are un timp de \u00eenjum\u0103t\u0103\u0163ire clasic ca celelalte medicamente, deorece acesta variaz\u0103 \u00een func\u0163ie de concentra\u0163ia sangvin\u0103. La o concentra\u0163ie de 15 mg\/L aproximativ o jum\u0103tate din cantitatea total\u0103 de fenitoin din organism va fi eliminat\u0103 \u00een decurs de 20 ore. Pe m\u0103sura ce nivelul sangvin se reduce rata de excre\u0163ie a medicamentului cre\u015fte.<\/span><\/p>\n

    Fenitoinul are un volum de distribu\u0163ie de 0.65 L\/kg fiind\u00a0legat \u00eentr-o propor\u0163ie de 90% de proteinele plasmatice, \u00een special de albumin\u0103.<\/span><\/p>\n

    Anumite reac\u0163ii adverse ale medicamentului se produc\u00a0\u00een intervalul terapeutic: hiperplazie gingivala, hiperglicemie, rash.<\/span><\/p>\n

    Farmacocinetic\u0103 fenitoinului este semnificativ afectat\u0103 de o serie de medicamente. Asa cum s-a men\u0163ionat, fenitoinul se administreaz\u0103 adesea \u00een combina\u0163ie cu fenobarbitalul. Induc\u0163ia sistemului enzimatic al citocromului P450 de c\u0103tre fenobarbital va cre\u015fte rata de metabolizare a fenitoinului. In steady state<\/em> induc\u0163ia enzimatic\u0103 va cre\u015fte rata de clearance astfel \u00eenc\u00e2t, pentru a men\u0163ine nivelul terapeutic, este necesar ca doza de fenitoin s\u0103 fie crescut\u0103 cu 30%.<\/span><\/p>\n

    Uremia exercit\u0103 un efect asupra leg\u0103rii fenitoinului de proteinele plasmatice. In faza uremic\u0103 se acumuleaz\u0103 produ\u015fii secundari de metabolism care leag\u0103 albumina \u015fi deplasez\u0103 fenitoinul, ceea ce duce la cre\u015fterea frac\u0163iunii libere.<\/span><\/p>\n

    Acidul valproic asociat fenitoinului intr\u0103 \u00een competi\u0163ie cu acesta pentru acela\u015fi situs de legare de pe albumin\u0103. Astfel, acidul valproic deplaseaz\u0103 fenitoinul de pe albumin\u0103 \u015fi conduce la cre\u015fterea frac\u0163iunii libere. Efectul global al administr\u0103riii simultane de acid valproic este acela ca nivelul total de fenitoin scade datorit\u0103 cre\u015fterii clearance-ului \u00eens\u0103 frac\u0163iunea liber\u0103 cre\u015fte; din acest motiv concentra\u0163ia fenitoinei libere, care reprezint\u0103 forma activ\u0103, r\u0103m\u00e2ne practic aceea\u015fi, nefiind necesar\u0103 ajustarea dozelor pentru men\u0163inerea aceluia\u015fi efect farmacologic.<\/span><\/p>\n

    In insuficien\u0163a renal\u0103 frac\u0163iunea liber\u0103 a fenitoinei nu poate fi usor eliminat\u0103, ceea ce conduce la cre\u015fterea at\u00e2t a frac\u0163iunii libere c\u00e2t \u015fi a nivelului total (frac\u0163iunea liber\u0103 cre\u015fte\u00a0 \u00eens\u0103 mai rapid dec\u00e2t concentra\u0163ia total\u0103); dozele trebuie reduse pentru evitarea toxicit\u0103\u0163ii.<\/span><\/p>\n

    Riscul de toxicitate este mare datorita modului particular de metabolizare a fenitoinului. Cre\u015fteri mici ale dozelor conduc la cre\u015fteri foarte mari ale concentra\u0163iei sangvine, astfel c\u0103 apar semne precoce ale toxicit\u0103\u0163ii: nistagmus, ataxie, dizartrie. Toxicitatea sever\u0103 apare la niveluri >30 mg\/L \u015fi se caracterizeaz\u0103 prin tremor, hiperreflexie \u015fi letargie. Totu\u015fi, spre deosebire de fenobarbital, consecin\u0163ele toxicit\u0103\u0163ii nu sunt grave, deoarece fenitoinul nu exercit\u0103 ac\u0163iuni deprimante asupra SNC3<\/sup>.<\/span><\/p>\n

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

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

    1. Laborator Synevo. Referin\u0163e specifice tehnologiei de lucru utilizate. 2010. Ref Type: Catalog.<\/span><\/div>\n
    2. Matthew R. Pincus, Naif Z. Abraham. Toxicology and Therapeutic Drug Monitoring. In Henry\u2019s Clinical Diagnosis and Management by Laboratory Methods, Saunders-Elsevier, 21st Edition, 2007, 308-320.<\/span><\/div>\n
    3.\u00a0<\/span>\u00a0Mayo Clinic\/Mayo Medical LaboratoriesTest Catalogs and Guides. Phenytoin, Serum. <\/span>www.mayomedicallaboratories.com. Ref Type: Internet Communication.<\/span><\/div>\n
    4. Quest Diagnostics. Therapeutic Drug Monitoring. Drug Half-Life, Steady State, and Recommended Sample Collection Time. www.questdiagnostics.com. Ref Type: Internet Communication.<\/span><\/div>","protected":false},"excerpt":{"rendered":"

    \u0424\u0435\u043d\u0438\u0442\u043e\u0438\u043d \u043e\u043a\u0430\u0437\u044b\u0432\u0430\u0435\u0442 \u043f\u0440\u043e\u0442\u0438\u0432\u043e\u0441\u0443\u0434\u043e\u0440\u043e\u0436\u043d\u043e\u0435 \u0434\u0435\u0439\u0441\u0442\u0432\u0438\u0435 \u0431\u0435\u0437 \u0432\u044b\u0440\u0430\u0436\u0435\u043d\u043d\u043e\u0433\u043e \u0441\u043d\u043e\u0442\u0432\u043e\u0440\u043d\u043e\u0433\u043e \u044d\u0444\u0444\u0435\u043a\u0442\u0430. \u0423\u0441\u0442\u0440\u0430\u043d\u044f\u0435\u0442 (50-90%) \u0441\u0443\u043f\u0440\u0430\u0432\u0435\u043d\u0442\u0440\u0438\u043a\u0443\u043b\u044f\u0440\u043d\u044b\u0435 \u0438 \u0436\u0435\u043b\u0443\u0434\u043e\u0447\u043a\u043e\u0432\u044b\u0435 \u0430\u0440\u0438\u0442\u043c\u0438\u0438, \u0432\u044b\u0437\u0432\u0430\u043d\u043d\u044b\u0435 \u043f\u0435\u0440\u0435\u0434\u043e\u0437\u0438\u0440\u043e\u0432\u043a\u043e\u0439 \u0441\u0435\u0440\u0434\u0435\u0447\u043d\u044b\u0445 \u0433\u043b\u0438\u043a\u043e\u0437\u0438\u0434\u043e\u0432, \u043d\u043e \u043c\u0430\u043b\u043e\u044d\u0444\u0444\u0435\u043a\u0442\u0438\u0432\u0435\u043d \u043f\u0440\u0438 \u0441\u0443\u043f\u0440\u0430\u0432\u0435\u043d\u0442\u0440\u0438\u043a\u0443\u043b\u044f\u0440\u043d\u044b\u0445 \u0430\u0440\u0438\u0442\u043c\u0438\u044f\u0445 \u0434\u0440\u0443\u0433\u043e\u0433\u043e \u0433\u0435\u043d\u0435\u0437\u0430. \u041f\u0440\u0438\u043c\u0435\u043d\u044f\u044e\u0442 \u043f\u0440\u0438 \u044d\u043f\u0438\u043b\u0435\u043f\u0441\u0438\u0438 (\u0431\u043e\u043b\u044c\u0448\u0438\u0435 \u0441\u0443\u0434\u043e\u0440\u043e\u0436\u043d\u044b\u0435 \u043f\u0440\u0438\u043f\u0430\u0434\u043a\u0438), \u0434\u043b\u044f \u043f\u0440\u043e\u0444\u0438\u043b\u0430\u043a\u0442\u0438\u043a\u0438 \u043f\u043e\u0441\u0442\u0442\u0440\u0430\u0432\u043c\u0430\u0442\u0438\u0447\u0435\u0441\u043a\u043e\u0439 \u0438 \u043f\u043e\u0441\u0442\u043d\u0435\u0439\u0440\u043e\u0445\u0438\u0440\u0443\u0440\u0433\u0438\u0447\u0435\u0441\u043a\u043e\u0439 \u044d\u043f\u0438\u043b\u0435\u043f\u0441\u0438\u0438, \u043f\u0440\u0438 \u0436\u0435\u043b\u0443\u0434\u043e\u0447\u043a\u043e\u0432\u044b\u0445 \u0430\u0440\u0438\u0442\u043c\u0438\u044f\u0445, \u0432 \u0442. \u0447. \u043f\u0440\u0438 \u0438\u043d\u0442\u043e\u043a\u0441\u0438\u043a\u0430\u0446\u0438\u0438 \u0441\u0435\u0440\u0434\u0435\u0447\u043d\u044b\u043c\u0438 \u0433\u043b\u0438\u043a\u043e\u0437\u0438\u0434\u0430\u043c\u0438, \u043d\u0435\u043a\u043e\u0442\u043e\u0440\u044b\u0445 \u0444\u043e\u0440\u043c\u0430\u0445 \u0441\u0438\u043d\u0434\u0440\u043e\u043c\u0430 \u041c\u0435\u043d\u044c\u0435\u0440\u0430, \u043f\u0440\u0438 \u043d\u0435\u0432\u0440\u0430\u043b\u0433\u0438\u0438 \u0442\u0440\u043e\u0439\u043d\u0438\u0447\u043d\u043e\u0433\u043e \u043d\u0435\u0440\u0432\u0430.<\/p>\n

    \u041f\u0440\u0438 \u043f\u0440\u0438\u0435\u043c\u0435 \u0432\u043d\u0443\u0442\u0440\u044c \u0432\u0441\u0430\u0441\u044b\u0432\u0430\u0435\u0442\u0441\u044f \u0441 \u0440\u0430\u0437\u043d\u043e\u0439 \u0441\u043a\u043e\u0440\u043e\u0441\u0442\u044c\u044e. \u041f\u0438\u043a \u043a\u043e\u043d\u0446\u0435\u043d\u0442\u0440\u0430\u0446\u0438\u0438 \u0432 \u043f\u043b\u0430\u0437\u043c\u0435 \u043a\u0440\u043e\u0432\u0438 \u043d\u0430\u0431\u043b\u044e\u0434\u0430\u0435\u0442\u0441\u044f \u0447\u0435\u0440\u0435\u0437 3-15 \u0447\u0430\u0441\u043e\u0432. \u0411\u043e\u043b\u0435\u0435 90% \u0444\u0435\u043d\u0438\u0442\u043e\u0438\u043d\u0430 \u0441\u0432\u044f\u0437\u044b\u0432\u0430\u0435\u0442\u0441\u044f \u0441 \u0431\u0435\u043b\u043a\u0430\u043c\u0438 \u043f\u043b\u0430\u0437\u043c\u044b \u043a\u0440\u043e\u0432\u0438. \u041f\u0435\u0440\u0438\u043e\u0434 \u043f\u043e\u043b\u0443\u0432\u044b\u0432\u0435\u0434\u0435\u043d\u0438\u044f \u0441\u043e\u0441\u0442\u0430\u0432\u043b\u044f\u0435\u0442 9-14 \u0447\u0430\u0441\u043e\u0432 \u043f\u0440\u0438 \u0432\u043d\u0443\u0442\u0440\u0438\u0432\u0435\u043d\u043d\u043e\u043c \u0432\u0432\u0435\u0434\u0435\u043d\u0438\u0438 \u0438 22-28 \u0447\u0430\u0441\u043e\u0432 \u043f\u0440\u0438 \u043f\u0435\u0440\u043e\u0440\u0430\u043b\u044c\u043d\u043e\u043c \u043f\u0440\u0438\u043c\u0435\u043d\u0435\u043d\u0438\u0438. \u041c\u0435\u043d\u0435\u0435 5% \u0432\u044b\u0434\u0435\u043b\u044f\u0435\u0442\u0441\u044f \u0441 \u043c\u043e\u0447\u043e\u0439 \u0432 \u043d\u0435\u0438\u0437\u043c\u0435\u043d\u0435\u043d\u043d\u043e\u043c \u0432\u0438\u0434\u0435, \u043e\u0441\u0442\u0430\u043b\u044c\u043d\u043e\u0435 \u043a\u043e\u043b\u0438\u0447\u0435\u0441\u0442\u0432\u043e \u043c\u0435\u0442\u0430\u0431\u043e\u043b\u0438\u0437\u0438\u0440\u0443\u0435\u0442\u0441\u044f \u0444\u0435\u0440\u043c\u0435\u043d\u0442\u0430\u043c\u0438 \u043f\u0435\u0447\u0435\u043d\u0438. \u041e\u0441\u043d\u043e\u0432\u043d\u043e\u0439 \u043c\u0435\u0442\u0430\u0431\u043e\u043b\u0438\u0442 \u043d\u0435\u0430\u043a\u0442\u0438\u0432\u0435\u043d, \u0432\u044b\u0434\u0435\u043b\u044f\u0435\u0442\u0441\u044f \u0441 \u0436\u0435\u043b\u0447\u044c\u044e, \u0430 \u0442\u0430\u043a\u0436\u0435 \u0441 \u043c\u043e\u0447\u043e\u0439 \u0432 \u0432\u0438\u0434\u0435 \u0433\u043b\u044e\u043a\u0443\u0440\u043e\u043d\u0438\u0434\u0430. \u0423\u0441\u0442\u043e\u0439\u0447\u0438\u0432\u0430\u044f \u043a\u043e\u043d\u0446\u0435\u043d\u0442\u0440\u0430\u0446\u0438\u044f \u043f\u0440\u0435\u043f\u0430\u0440\u0430\u0442\u0430 \u0432 \u043a\u0440\u043e\u0432\u0438 \u0443\u0441\u0442\u0430\u043d\u0430\u0432\u043b\u0438\u0432\u0430\u0435\u0442\u0441\u044f \u043d\u0430 5-14 \u0434\u0435\u043d\u044c.<\/p>\n

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    \u041e\u0446\u0435\u043d\u043a\u0443 \u0443\u0440\u043e\u0432\u043d\u044f \u0444\u0435\u043d\u0438\u0442\u043e\u0438\u043d\u0430 \u0432 \u0441\u044b\u0432\u043e\u0440\u043e\u0442\u043a\u0435 \u043a\u0440\u043e\u0432\u0438 \u043f\u0440\u0438\u043c\u0435\u043d\u044f\u044e\u0442 \u0432 \u0446\u0435\u043b\u044f\u0445 \u0438\u043d\u0434\u0438\u0432\u0438\u0434\u0443\u0430\u043b\u044c\u043d\u043e\u0433\u043e \u043f\u043e\u0434\u0431\u043e\u0440\u0430 \u0434\u043e\u0437\u044b \u0438 \u043f\u0435\u0440\u0438\u043e\u0434\u0438\u0447\u0435\u0441\u043a\u043e\u0433\u043e \u043a\u043e\u043d\u0442\u0440\u043e\u043b\u044f \u0442\u0435\u0440\u0430\u043f\u0438\u0438 (\u0432 \u0442. \u0447. \u043f\u0440\u0438 \u0434\u043e\u0431\u0430\u0432\u043b\u0435\u043d\u0438\u0438 \u0434\u0440\u0443\u0433\u0438\u0445 \u043b\u0435\u043a\u0430\u0440\u0441\u0442\u0432, \u0441\u043c\u0435\u043d\u0435 \u0444\u043e\u0440\u043c\u044b \u043f\u0440\u0435\u043f\u0430\u0440\u0430\u0442\u0430 \u0438 \u0434\u0440\u0443\u0433\u0438\u0445 \u043f\u043e\u043a\u0430\u0437\u0430\u043d\u0438\u044f\u0445).<\/p>\n

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    \u0423\u0441\u043b\u043e\u0432\u0438\u044f \u0432\u0437\u044f\u0442\u0438\u044f \u043f\u0440\u043e\u0431\u044b \u043e\u043f\u0440\u0435\u0434\u0435\u043b\u044f\u044e\u0442\u0441\u044f \u043b\u0435\u0447\u0430\u0449\u0438\u043c \u0432\u0440\u0430\u0447\u043e\u043c \u0432 \u0441\u043e\u043e\u0442\u0432\u0435\u0442\u0441\u0442\u0432\u0438\u0438 \u0441 \u0446\u0435\u043b\u044f\u043c\u0438 \u0438\u0441\u0441\u043b\u0435\u0434\u043e\u0432\u0430\u043d\u0438\u044f.<\/p>","protected":false},"featured_media":0,"comment_status":"closed","ping_status":"closed","template":"","meta":[],"product_brand":[],"product_cat":[984],"product_tag":[],"class_list":{"0":"post-10320","1":"product","2":"type-product","3":"status-publish","5":"product_cat-monitorizare-terapeutica-medicamente-tdm","7":"first","8":"instock","9":"sold-individually","10":"shipping-taxable","11":"purchasable","12":"product-type-simple"},"_links":{"self":[{"href":"https:\/\/old.synevo.md\/ru\/wp-json\/wp\/v2\/product\/10320","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=10320"}],"wp:attachment":[{"href":"https:\/\/old.synevo.md\/ru\/wp-json\/wp\/v2\/media?parent=10320"}],"wp:term":[{"taxonomy":"product_brand","embeddable":true,"href":"https:\/\/old.synevo.md\/ru\/wp-json\/wp\/v2\/product_brand?post=10320"},{"taxonomy":"product_cat","embeddable":true,"href":"https:\/\/old.synevo.md\/ru\/wp-json\/wp\/v2\/product_cat?post=10320"},{"taxonomy":"product_tag","embeddable":true,"href":"https:\/\/old.synevo.md\/ru\/wp-json\/wp\/v2\/product_tag?post=10320"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}