{"id":10129,"date":"2020-04-23T04:57:27","date_gmt":"2020-04-23T01:57:27","guid":{"rendered":"https:\/\/www.synevo.ro\/product\/tacrolimus-in-sange\/"},"modified":"2025-02-07T16:49:10","modified_gmt":"2025-02-07T14:49:10","slug":"tacrolimus-in-sange","status":"publish","type":"product","link":"https:\/\/old.synevo.md\/ru\/shop\/tacrolimus-in-sange\/","title":{"rendered":"\u0422\u0430\u043a\u0440\u043e\u043b\u0438\u043c\u0443\u0441 \u0432 \u043a\u0440\u043e\u0432\u0438"},"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 \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 \u015fi uniforme a medicamentului\u00a0\u00een organism (cinetica de ordinul I), precum \u015fi\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>\u00a0pentru a ob\u0163ine steady state<\/em> (vezi fig. 20.3.1<\/em>)1;2;4<\/sup>.<\/span><\/p>\n

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

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

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

\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<\/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, \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\u0163iei 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 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><\/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 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

    Metod\u0103 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 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

    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

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

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

    8-20 mg\/L<\/span>\u00a0<\/span><\/p>\n<\/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

    		\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) 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<\/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

    		\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

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

    		\n

    50-100 mg\/L<\/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

    		\n

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

    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><\/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

    \u00a0<\/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

    		\n

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

    \u00a0<\/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\u00a0 camerei; 24 ore<\/em> la 2-8\u00b0C; 6 luni<\/em> la -18\u00b0C<\/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 Protec\u0163ie impotriva viitoarelor episoade la pacien\u0163ii cu afec\u0163iune 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 s\u0103pt\u0103m\u00e2ni<\/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 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

    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 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

    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

    S\u00e2nge 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 variaz\u0103 \u00een func\u0163ie de tipul transplantului \u015fi perioada de timp de la transplant. Pentru afec\u0163iuni dermatologice \u015fi reumatologice:<100 \u00b5g\/L<\/span><\/p>\n

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

    \n

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

    		\n

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

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

    		\n

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

    		\n

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

    		\n

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

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

    		\n

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

    		\n

    \u2013\u00a0\u00een primele 2 luni de la transplant:<\/strong><\/span><\/p>\n

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

    \u2013 dup\u0103\u00a02 luni de la transplant:<\/strong><\/span><\/p>\n

    8-15 \u00b5g\/L<\/strong><\/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

    S\u00e2nge 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

    Cinetica 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><\/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 asociaz\u0103 cu un risc crescut de toxicitate:<\/span><\/p>\n

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

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

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

    ECLIA = metoda imunochimic\u0103 cu detec\u0163ie prin chemiluminiscen\u0163\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

    Medicamente imunosupresoare<\/span><\/strong><\/span><\/p>\n

    In timp ce integritatea r\u0103spunsului imun umoral \u015fi celular este esen\u0163ial\u0103 pentru prevenirea infec\u0163iilor, \u00een unele situa\u0163ii, cum ar fi bolile autoimune \u015fi transplantul de organe solide, devine vital s\u0103 se suprime activitatea acestor sisteme.<\/span><\/p>\n

    In statusul post-transplant este implicat\u0103 imunitatea de tip celular. Atat\u00a0\u00een cazul reac\u0163iilor grefa-contra-gazd\u0103 cat \u015fi a celor gazd\u0103-contra-gref\u0103 limfocitele T CD4+ sunt activate atunci cand un antigen str\u0103in se leag\u0103 de antigenele HLA clasa a II-a de pe suprafa\u0163a macrofagelor (celulele prezentatoare de antigen). Clonele de celule T specifice se vor lega de antigen prin intermediul receptorului celulei T (TCR); activarea TCR rezult\u0103 \u00eentr-o \u201ccascada\u201d de transduc\u0163ie a semnalului care va conduce\u00a0\u00een final la endocitoza antigenului\u00a0\u00een macrofage \u015fi distrugerea acestuia\u00a0\u00een lizozomi. In aceast\u0103 cascad\u0103 sunt mobilizati ionii de calciu care determin\u0103 activarea calcineurinei, o fosfataz\u0103 ce formeaz\u0103 un complex cu calmodulinul. Calcineurina activat\u0103 defosforileaz\u0103 factorul nuclear citosolic al celulelor T activate (NF-AT)\u0412<\/sup> si astfel \u00eel activeaz\u0103; acesta migreaz\u0103 c\u0103tre nucleu \u015fi se leag\u0103 de omologul s\u0103u (NF-AT)\u041d<\/sup>. Complexul transcrip\u0163ional activ rezultat va induce sinteza de interleukin\u0103-2 (IL-2) care va fi secretat\u0103 ca un mitogen extracelular. IL-2 se leag\u0103 de receptorul s\u0103u situat pe limfocitul T, pe care \u00eel activeaz\u0103 prin legarea unei proteine, denumit\u0103 \u201c\u0163int\u0103 rapamicinei\u201d (target of rapamycin = TOR); aceast\u0103 protein\u0103 activeaz\u0103 ciclin-kinazele care faciliteaz\u0103 progresia ciclului celular din G1 in S \u015fi stimuleaz\u0103 sinteza nucleotidelor. Procesul are ca rezultat diferen\u0163ierea \u015fi proliferarea celulelor T \u015fi va conduce \u00een final la distrugerea antigenului.<\/span><\/p>\n

    Au fost dezvoltate medicamente specifice care blocheaz\u0103 una sau mai multe din etapele men\u0163ionate mai sus, inhiband astfel distrugerea antigenului.<\/span><\/p>\n

    Ciclosporina \u015fi tacrolimusul sunt polipeptide ciclice care se leag\u0103 de proteinele intracelulare denumite imunofiline (ciclosporina se leag\u0103 de ciclofilin\u0103, \u00een timp ce tacrolimusul se leag\u0103 de imunofilina denumit\u0103 FKBP12), rezultand complexe ce blocheaz\u0103 ulterior activarea NF-AT indus\u0103 de calcineurin\u0103 \u015fi \u00een consecin\u0163\u0103 sinteza de IL-2.<\/span><\/p>\n

    Un alt agent imunosupresor \u2013 rapamicin\u0103 (sirolimus) \u2013 nu exercit\u0103 nici un efect asupra celulelor T, \u00een schimb se leag\u0103 de protein\u0103 TOR cu rol critic \u00een activarea celulei T.<\/span><\/p>\n

    Micofenolatul mofetil (MMT) este un antibiotic ce este hidrolizat \u00een celule \u00een acid micofenolic liber. Acest agent este un inhibitor potent al inozin-monofosfat dehidrogenazei \u015fi al guanozin-monofosfat sintetazei, \u00eempiedicand \u00een final sinteza ADN-ului.<\/span><\/p>\n

    Corticosteroizii exercit\u0103 de asemenea efecte imunosupresoare asupra imunit\u0103\u0163ii mediate celular, dar acestea sunt mult mai pu\u0163in specifice \u015fi inso\u0163ite de numeraose reac\u0163ii adverse2<\/sup>.<\/span><\/p>\n

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

    Este un antibiotic din clasa macrolidelor cu un mecanism de actiune similar ciclosporinei, dar cu un efect inhibitor mai potent decat acesta. Este utilizat \u00een prevenirea rejetului de organ.<\/span><\/p>\n

    Tacrolimus este metabolizat \u00een ficat de c\u0103tre CYP3A4, astfel c\u0103 nivelurile sale \u00een sange sunt afectate atat de medicamentele care inhib\u0103 aceast\u0103 enzim\u0103 (blocante ale canalelor de calciu, antifungice, unele antibiotice), cat \u015fi de cele care induc activitatea enzimatic\u0103 (anticonvulsivante, rifampicina).<\/span><\/p>\n

    Deoarece 90% din tacrolimus se g\u0103se\u015fte\u00a0\u00een componentele celulare din sange se recomand\u0103 ca nivelurile medicamentului s\u0103 fie determinate\u00a0\u00een probe de sange integral. Concentra\u0163iile ob\u0163inute\u00a0\u00een trough samples<\/em> pot varia \u00een func\u0163ie de protocolul clinic, tipul alogrefei, riscul de rejet, administrarea concomitent\u0103 a unor alte imunosupresoare \u015fi toxicitate (\u00een principal nefrotoxicitate), \u00eens\u0103 nu trebuie sa dep\u0103\u015feasc\u0103 20 \u00b5g\/L.<\/span><\/p>\n

    Poten\u0163ialul toxic este similar celui al ciclosporinei: nefrotoxicitate, neurotoxicitate (tremor, cefalee), tulbur\u0103ri gastrointestinale (grea\u0163\u0103, diaree), HTA, perturbarea metabolismului glucozei, hiperkaliemie \u015fi complica\u0163ii infec\u0163ioase. Totu\u015fi nu apare hipertrofie gingival\u0103 \u015fi nici hirsutism. Anafilaxia este descris\u0103 numai\u00a0\u00een cazul administr\u0103rii intravenoase2;3<\/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 <\/span>and Management by Laboratory Methods, Saunders-Elsevier, 21st Edition, 2007, 308-320.<\/span><\/div>\n
    3. Mayo Clinic\/Mayo Medical LaboratoriesTest Catalogs and Guides. Tacrolimus, Blood. <\/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 <\/span>Collection Time. www.questdiagnostics.com. Ref Type: Internet Communication.<\/span><\/div>","protected":false},"excerpt":{"rendered":"

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