{"id":10166,"date":"2020-04-23T04:58:30","date_gmt":"2020-04-23T01:58:30","guid":{"rendered":"https:\/\/www.synevo.ro\/product\/acid-valproic\/"},"modified":"2025-02-07T16:46:00","modified_gmt":"2025-02-07T14:46:00","slug":"acid-valproic","status":"publish","type":"product","link":"https:\/\/old.synevo.md\/ru\/shop\/acid-valproic\/","title":{"rendered":"\u0412\u0430\u043b\u044c\u043f\u0440\u043e\u0435\u0432\u0430\u044f \u043a\u0438\u0441\u043b\u043e\u0442\u0430"},"content":{"rendered":"

Informa\u021bii generale \u0219i recomand\u0103ri pentru testare<\/i><\/b><\/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 \u00ee\u015fi 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 \u015fi 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\u00a0\u00een a\u015fa 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 \u015fi excre\u0163ie. In condi\u0163iile unei distribu\u0163ii rapide\u00a0\u015fi uniforme a medicamentului\u00a0\u00een organism (cinetica de ordinul I), precum\u00a0\u015fi \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><\/p>\n

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

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

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

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

D\u2192E\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0 D = concentra\u0163ia medicamentului\u00a0 E = forma excretata 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 k = constanta de dispari\u0163ie a lui D<\/span><\/p>\n

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

A\u015fa cum reiese din ecua\u0163ie, T1\/2<\/sub> este o constant\u0103\u00a0<\/sub>\u015fi nu depinde de concentra\u0163ia medicamentului. Daca T1\/2 <\/sub>este cunoscut se poate calcula modul de \u00eemp\u0103r\u0163ire a dozelor \u015fi intervalul de timp la care trebuie administrate pentru a se atinge nivelul terapeutic.<\/span><\/p>\n

Totu\u015fi, 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\u00a0\u015fi o rat\u0103 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,\u00a0\u00een cazurile\u00a0\u00een care se modific\u0103 dozele administrate \u015fi se adaug\u0103 sau se scot medicamente asociate, se va a\u015ftepta ob\u0163inerea unei noi st\u0103ri de echilibru \u00eenainte de recoltarea probei pentru monitorizarea terapeutic\u0103. Intr-un mod similar, se va a\u015ftepta aceea\u015fi 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

-\u00een momentul nivelului maxim (peak samples<\/em>): la 2-3 ore dup\u0103 administrarea unei doze orale, la 30-60 minute dup\u0103 o doz\u0103 administrat\u0103 intravenos, la 2-4 ore dup\u0103 o doz\u0103 administrat\u0103 intramuscular sau la 1-1 \u015fi \u00bd ore dup\u0103 o doz\u0103 administrat\u0103 intranazal;<\/span><\/p>\n

-\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\u0163ei doz\u0103-efect;<\/span><\/div>\n
\u2022 e\u015fec \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 \u015fi excre\u0163ia medicamentelor;<\/span><\/div>\n
\u2022 administrarea simultan\u0103 de medicamente care prezint\u0103 aceea\u015fi cale de eliminare;<\/span><\/div>\n
\u2022 copii \u015fi persoane v\u00e2rstnice la care este afectat volumul de distribu\u0163ie: redus \u00een cazul v\u00e2rstnicilor \u015fi 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 infectia 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 \u015fi 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 pana la steady state<\/strong><\/span><\/p>\n<\/td>\n

    		\n

    Tip proba<\/strong><\/span><\/p>\n<\/td>\n

    		\n

    Stabilitate proba<\/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

    		\n

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

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

    		\n

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

    		\n

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

    \n

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

    		\n

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

    		\n

    Nu se aplica<\/span><\/p>\n<\/td>\n

    		\n

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

    		\n

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

    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

    \n

    Flecainida<\/span><\/p>\n<\/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><\/p>\n

    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

    \n

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

    		\n

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

    1-8 ore (copil)<\/span><\/p>\n

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

    		\n

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

    5-40 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><\/p>\n

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

    		\n

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

    		\n

    < 1 an:<\/span><\/p>\n

    5-10 mg\/L<\/span><\/p>\n

    \u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u2265 1 an:\u00a0\u00a0\u00a0<\/span><\/p>\n

    8-20 mg\/L<\/span><\/p>\n

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

    \n

    \u0412\u0430\u043d\u043a\u043e\u043c\u0438\u0446\u0438\u043d<\/span><\/p>\n<\/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><\/p>\n

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

    		\n

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

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

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

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

    		\n

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

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

    		\n

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

    2-4 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><\/p>\n

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

    		\n

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

    		\n

    50-100 mg\/L<\/strong><\/span><\/p>\n<\/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

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

    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<\/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><\/p>\n

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

    		\n

    18-22 ore (adult);<\/span><\/p>\n

    7-29 ore (copil)<\/span><\/p>\n<\/td>\n

    		\n

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

    2-5 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><\/p>\n

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

    		\n

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

    		\n

    <14 ani:<\/span><\/p>\n

    10-20 mg\/L<\/span><\/p>\n

    >14 ani:<\/span><\/p>\n

    6-14 mg\/L<\/span><\/p>\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

    		\n

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

    		\n

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

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

    		\n

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

    		\n

    2 \u2013 10 \u00b5g\/mL<\/span><\/p>\n<\/td>\n<\/tr>\n

    \n

    \u041b\u0430\u043c\u043e\u0442\u0440\u0438\u0434\u0436\u0438\u043d<\/span><\/p>\n<\/td>\n

    		\n

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

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

    		\n

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

    3-10 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><\/p>\n

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

    		\n

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

    		\n

    <14 ani:<\/span><\/p>\n

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

    >14 ani:<\/span><\/p>\n

    1-5 mg\/L<\/span><\/p>\n<\/td>\n<\/tr>\n

    \n

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

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

    		\n

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

    		\n

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

    		\n

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

    		\n

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

    		\n

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

    		\n

    50-300 \u00b5g\/L<\/span><\/p>\n<\/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; 24 ore<\/em> la 2-8\u00b0C; 6 luni<\/em> la -18\u00b0C.<\/span><\/span><\/p>\n<\/td>\n

    		\n

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

    		\n

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

    \u2022 Protectie impotriva viitoarelor episoade la pacientii cu afectiune bipolara: 0.8-1.0 mmol\/L.<\/span><\/p>\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

    		\n

    3 saptamani<\/span><\/p>\n<\/td>\n

    		\n

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

    		\n

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

    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

    		\n

    4-66 ore<\/span><\/p>\n<\/td>\n

    		\n

    Nu se aplica<\/span><\/p>\n<\/td>\n

    		\n

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

    		\n

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

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

    		\n

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

    \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

    		\n

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

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

    		\n

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

    		\n

    \u00a010-80 \u00b5g\/L<\/span><\/p>\n<\/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><\/p>\n

    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

    		\n

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

    		\n

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

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

    		\n

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

    		\n

    45-150 \u00b5g\/L<\/span><\/p>\n<\/td>\n<\/tr>\n

    \n

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

    		\n

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

    		\n

    14 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><\/p>\n

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

    		\n

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

    		\n

    125-200 \u00b5g\/L<\/span><\/p>\n<\/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><\/p>\n

    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

    \n

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

    		\n

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

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

    		\n

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

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

    		\n

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

    		\n

    5-16 \u00b5g\/L<\/span><\/p>\n<\/td>\n<\/tr>\n

    \n

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

    		\n

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

    		\n

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

    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

    Sange EDTA<\/span><\/p>\n<\/td>\n

    		\n

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

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

    		\n

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

    		\n

    Intervalul terapeutic variaza in functie de tipul transplantului si perioada de timp de la transplant.<\/span><\/p>\n

    Pentru afectiuni dermatologice si reumatologice:<100 \u00b5g\/L<\/span><\/p>\n

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

    \n

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

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

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

    		\n

    2-6 zile (adult); nu se aplic\u0103 la copil<\/span><\/p>\n<\/td>\n

    		\n

    Sange EDTA<\/span><\/p>\n<\/td>\n

    		\n

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

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

    		\n

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

    		\n

    \u2013 in primele 2 luni de la transplant:<\/span><\/p>\n

    15-20 \u00b5g\/L<\/span><\/p>\n

    \u2013 dupa<\/span><\/p>\n

    \u00a02 luni de la transplant:<\/span><\/p>\n

    8-15 \u00b5g\/L<\/span><\/p>\n<\/td>\n<\/tr>\n

    \n

    \u0421\u0438\u0440\u043e\u043b\u0438\u043c\u0443\u0441 \u0432 \u043a\u0440\u043e\u0432\u0438<\/span><\/p>\n<\/td>\n

    		\n

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

    		\n

    5-7 zile<\/span><\/p>\n<\/td>\n

    		\n

    Sange EDTA<\/span><\/p>\n<\/td>\n

    		\n

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

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

    		\n

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

    		\n

    4-20 \u00b5g\/L<\/span><\/p>\n<\/td>\n<\/tr>\n

    \n

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

    		\n

    8-18 ore (adult); 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

    		\n

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

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

    		\n

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

    		\n

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

    \n

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

    		\n

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

    		\n

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

    		\n

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

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

    		\n

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

    la 2-8\u00b0C protejat de lumin\u0103<\/span><\/p>\n<\/td>\n

    		\n

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

    		\n

    Se asociaza 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><\/p>\n<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

    ECLIA = metoda 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 (metoda imunochimic\u0103 cu detec\u0163ie prin fluorescent\u0103 polarizat\u0103)<\/span><\/p>\n

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

    ISE = ion selective electrode (metoda 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

    Acidul valproic<\/strong> este utilizat \u00een tratamentul crizelor epieptice de tip absen\u0163\u0103 simpl\u0103 sau complex\u0103 \u015fi pentru controlul crizelor generalizate, care includ crize de absen\u0163\u0103, \u00een asociere cu alte anticonvulsivante.<\/span><\/p>\n

    Dozele ini\u0163iale de acid valproic sunt de 15 mg\/kg corp\/zi, dar pot fi crescute progresiv p\u00e2n\u0103 la maximum 60 mg\/kg corp\/zi.<\/span><\/p>\n

    Au fost descrise reac\u0163ii adverse grave cum ar fi insuficien\u0163a hepatic\u0103 sau un sindrom similar sindromului Reye produse \u00een intervalul terapeutic. Din acest motiv este obligatorie monitorizarea atent\u0103 a func\u0163iei hepatice \u00een cursul primelor 6 luni de tratament.<\/span><\/p>\n

    Acidul valproic are un volum de distribu\u0163ie de 0.2 L\/kg \u015fi un timp de \u00eenjum\u0103t\u0103\u0163ire de 9-16 ore la adult \u015fi mai scurt la copil. Se leag\u0103 \u00een propor\u0163ie de 90% de proteinele plasmatice.<\/span><\/p>\n

    Acest medicament exercit\u0103 efecte substan\u0163iale asupra farmacologiei fenitoinului, \u00een timp ce fenitoinul are un efect limitat asupra valproatului.<\/span><\/p>\n

    Principalele reac\u0163ii adverse apar la valori ale nivelului seric maxim (peak samples<\/em>) >125 mg\/L \u015fi includ: depresie SNC, trombocitopenie, disfunc\u0163ie hepatic\u01033<\/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. Mayo Clinic\/Mayo Medical LaboratoriesTest Catalogs and Guides. Valproic Acid, Total, Serum. 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":"

    \u0428\u0438\u0440\u043e\u043a\u043e \u0438\u0441\u043f\u043e\u043b\u044c\u0437\u0443\u0435\u043c\u044b\u0439 \u043f\u0440\u0435\u043f\u0430\u0440\u0430\u0442 \u0434\u043b\u044f \u043b\u0435\u0447\u0435\u043d\u0438\u044f \u0441\u0443\u0434\u043e\u0440\u043e\u0436\u043d\u044b\u0445 \u0440\u0430\u0441\u0441\u0442\u0440\u043e\u0439\u0441\u0442\u0432 \u0443 \u0432\u0437\u0440\u043e\u0441\u043b\u044b\u0445 \u0438 \u0434\u0435\u0442\u0435\u0439.<\/p>\n

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