{"id":10128,"date":"2020-04-23T04:57:25","date_gmt":"2020-04-23T01:57:25","guid":{"rendered":"https:\/\/www.synevo.ro\/product\/ciclosporina-a-in-sange\/"},"modified":"2025-02-07T16:48:41","modified_gmt":"2025-02-07T14:48:41","slug":"ciclosporina-a-in-sange","status":"publish","type":"product","link":"https:\/\/old.synevo.md\/ru\/shop\/ciclosporina-a-in-sange\/","title":{"rendered":"\u0426\u0438\u043a\u043b\u043e\u0441\u043f\u043e\u0440\u0438\u043d \u0410 \u0432 \u043a\u0440\u043e\u0432\u0438"},"content":{"rendered":"<p style=\"text-align: justify;\"><span style=\"font-size: medium;\"><strong><em>Informa\u0163ii generale \u015fi recomand\u0103ri pentru testare<\/em><\/strong><\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\">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<p style=\"text-align: justify;\"><span style=\"font-size: medium;\">Monitorizarea terapeutic\u0103 a unui medicament (Therapeutic Drug Monitoring, TDM) are drept scop men\u0163inerea concentra\u0163iei acestuia \u00een <strong>intervalul terapeutic<\/strong>, definit ca acel interval de valori ale nivelului in ser, plasm\u0103 sau s\u00e2nge integral \u00een care medicamentul respectiv i\u015fi exercit\u0103 efectele clinice cu reac\u0163ii adverse minime pentru majoritatea pacien\u0163ilor.<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\">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<p style=\"text-align: justify; padding-left: 30px;\"><span style=\"font-size: medium;\">-<span style=\"text-decoration: underline;\">farmacocinetic\u0103<\/span>: studiaz\u0103 efectele medicamentului asupra organismului (rela\u0163ia doz\u0103-efect);<\/span><\/p>\n<p style=\"text-align: justify; padding-left: 30px;\"><span style=\"font-size: medium;\">-<span style=\"text-decoration: underline;\">farmacodinamica<\/span>: studiaz\u0103 efectele organismului asupra medicamentelor (absorb\u0163ie, distribu\u0163ie etc);<strong><em>\u00a0<\/em><\/strong><\/span><\/p>\n<p style=\"text-align: justify; padding-left: 30px;\"><span style=\"font-size: medium;\">-<span style=\"text-decoration: underline;\">farmacogenetica<\/span>: studiaz\u0103 modelul genetic al metaboliz\u0103rii medicamentelor lu\u00e2nd \u00een considerare varia\u0163iile individuale.<strong><em>\u00a0<\/em><\/strong><\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\">Pentru a ob\u0163ine rezultate pentru concentra\u0163iile medicamentoase cu utilitate clinic\u0103 este important ca proba s\u0103 fie recoltat\u0103 \u00een a\u015fa numita <strong>\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 <em>steady state<\/em> depinde de\u00a0 <strong>timpul de \u00eenjum\u0103t\u0103\u0163ire al medicamentului (T<sub>1\/2<\/sub>)<\/strong>, adic\u0103 timpul \u00een care concentra\u0163ia medicamentului \u00een s\u00e2nge se reduce la jum\u0103tate. La r\u00e2ndul s\u0103u T<sub>1\/2 <\/sub>depinde de rata de metabolizare \u015fi excre\u0163ie. In condi\u0163iile unei distribu\u0163ii rapide \u015fi uniforme a medicamentului \u00een organism (cinetic\u0103 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 T<sub>1\/2<\/sub>\u00a0 pentru a ob\u0163ine <em>steady state<\/em> (<em>vezi fig. 20.3.1<\/em>)<sup>1;2;4<\/sup>.<\/span><span style=\"font-size: medium;\"><a title=\"\" href=\"\/wp-content\/uploads\/2009\/08\/mediacam.jpg\" rel=\"wpdevart_lightbox lightbox-gallery-avxmq6lg\" data-=\"\" data-rl_title=\"\" data-rl_caption=\"\"><img decoding=\"async\" class=\"alignnone size-full wp-image-8516\" src=\"\/wp-content\/uploads\/2009\/08\/mediacam.jpg\" alt=\"-\" width=\"497\" height=\"298\"><\/a><\/span><\/p>\n<p><a class=\"shutterset_4215 cboxElement\" title=\"\u0426\u0438\u043a\u043b\u043e\u0441\u043f\u043e\u0440\u0438\u043d \u0410 \u0432 \u043a\u0440\u043e\u0432\u0438\" href=\"https:\/\/www.synevo.md\/wp-content\/uploads\/2009\/08\/mediacam.jpg\" rel=\"wpdevart_lightbox lightbox[4215] nofollow noopener\" data-rel=\"lightbox-gallery-0loVI9Zj\" data-rl_title=\"\" data-rl_caption=\"\" target=\"_blank\"><img decoding=\"async\" class=\"alignnone size-full wp-image-8516\" src=\"\/wp-content\/uploads\/2009\/08\/mediacam.jpg\" alt=\"-\" width=\"497\" height=\"298\"><\/a><\/p>\n<p>Fig. 20.3.1 Ob\u0163inerea\u00a0<strong>\u201e<\/strong>steady state<strong>\u201d<\/strong><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\">Acest proces poate fi rezumat astfel:<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\">\u00a0\u00a0 k\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0 <span style=\"font-size: 12pt;\">k = constanta de dispari\u0163ie a lui D<\/span><\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\">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<p style=\"text-align: justify;\"><span style=\"font-size: medium;\">\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0 <\/span><span style=\"font-size: medium;\">\u0423<sub>1\/2<\/sub> = 0.693\/k<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\">A\u015fa cum reiese din ecua\u0163ie, T<sub>1\/2 <\/sub>este o constant\u0103<sub>\u00a0\u00a0<\/sub>\u015fi nu depinde de concentra\u0163ia medicamentului. Dac\u0103 T<sub>1\/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<p style=\"text-align: justify;\"><span style=\"font-size: medium;\">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 \u015fi o rat\u0103 diferit\u0103 de distribu\u0163ie tisular\u0103). In aceste cazuri, timpul necesar pentru a atinge <em>steady state <\/em>poate s\u0103 fie diferit de echivalentul a 5 T<sub>1\/2<\/sub> .<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\">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 <em>steady state <\/em>se va elimina din organism la \u00eentreruperea administr\u0103rii<sup>2<\/sup>.<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\">Odat\u0103 atins\u0103 starea de echilibru, probele de s\u00e2nge pot fi recoltate \u00een dou\u0103 momente diferite:<\/span><\/p>\n<p style=\"text-align: justify; padding-left: 30px;\"><span style=\"font-size: medium;\">-\u00een momentul nivelului maxim (<em>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 si \u00bd ore dup\u0103 o doz\u0103 administrat\u0103 intranazal;<\/span><\/p>\n<p style=\"text-align: justify; padding-left: 30px;\"><span style=\"font-size: medium;\">-\u00een momentul nivelului minim (<em>trough samples<\/em>): imediat \u00eenaintea administr\u0103rii urm\u0103toarei doze; acest moment este recomandat \u00een majoritatea cazurilor.<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\">Monitorizarea terapeutic\u0103 a medicamentelor este indicat\u0103 \u00een special \u00een urm\u0103toarele situa\u0163ii:<\/span><\/p>\n<p style=\"text-align: justify; padding-left: 30px;\"><span style=\"font-size: medium;\">\u2022 perturbarea rela\u0163iei doz\u0103-efect;<\/span><\/p>\n<p style=\"text-align: justify; padding-left: 30px;\"><span style=\"font-size: medium;\">\u2022 e\u015fec \u00een ob\u0163inerea efectului terapeutic sau suspectarea unei intoxica\u0163ii;<\/span><\/p>\n<p style=\"text-align: justify; padding-left: 30px;\"><span style=\"font-size: medium;\">\u2022 efect imposibil sau foarte greu de confirmat clinic (de exemplu \u00een cazul imunosupresoarelor);<\/span><\/p>\n<p style=\"text-align: justify; padding-left: 30px;\"><span style=\"font-size: medium;\">\u2022 interval terapeutic \u00eengust (de exemplu \u00een cazul glicozidelor);<\/span><\/p>\n<p style=\"text-align: justify; padding-left: 30px;\"><span style=\"font-size: medium;\">\u2022 complian\u0163a redus\u0103 a pacien\u0163ilor (persoane v\u00e2rstnice sau cu boli psihice);<\/span><\/p>\n<p style=\"text-align: justify; padding-left: 30px;\"><span style=\"font-size: medium;\">\u2022 prezen\u0163a unor afec\u0163iuni care afecteaz\u0103 absorb\u0163ia, distribu\u0163ia, metabolizarea \u015fi excre\u0163ia medicamentelor;<\/span><\/p>\n<p style=\"text-align: justify; padding-left: 30px;\"><span style=\"font-size: medium;\">\u2022 administrarea simultan\u0103 de medicamente care prezint\u0103 aceea\u015fi cale de eliminare;<\/span><\/p>\n<p style=\"text-align: justify; padding-left: 30px;\"><span style=\"font-size: medium;\">\u2022 copii \u015fi persoane v\u00e2rstnice la care este afectat volumul de distribu\u0163ie: redus \u00een cazul v\u00e2rstnicilor \u015fi crescut la copii.<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\">Clasele de medicamente pentru care se recomand\u0103 \u00een mod special TDM sunt urm\u0103toarele:<\/span><\/p>\n<ul style=\"text-align: justify;\">\n<li><span style=\"font-size: medium;\">glicozide cardiace: digoxin, digitoxin;<\/span><\/li>\n<li><span style=\"font-size: medium;\">antiaritmice:\u00a0 amiodarona, flecainida, procainamida, chinidina;<\/span><\/li>\n<li><span style=\"font-size: medium;\">antiastmatice: teofilina;<\/span><\/li>\n<li><span style=\"font-size: medium;\">antibiotice: aminoglicozide, vancomicina;<\/span><\/li>\n<li><span style=\"font-size: medium;\">antivirale: medicamentele pentru infec\u0163ia HIV, ganciclovir;<\/span><\/li>\n<li><span style=\"font-size: medium;\">anticonvulsivante: fenobarbital, carbamazepin, fenitoin, acid valproic, gabapentin, primidona, lamotrigin;<\/span><\/li>\n<li><span style=\"font-size: medium;\">medicamente psihotrope: litiu, antidepresive triciclice, neuroleptice;<\/span><\/li>\n<li><span style=\"font-size: medium;\">imunosupresoare: ciclosporina, tacrolimus, sirolimus, everolimus, acid micofenolic, azatioprina;<\/span><\/li>\n<li><span style=\"font-size: medium;\">citostatice: methotrexat<sup>1;2<\/sup>.<\/span><\/li>\n<\/ul>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\">In tabelul de mai jos sunt precizate, pentru anumite medicamente T<sub>1\/2<\/sub>, intervalul de timp necesar pentru a se ajunge la <em>steady state<\/em>, tipul de prob\u0103 pentru TDM \u015fi stabilitatea acesteia, intervalul terapeutic<sup>1;4<\/sup>:<\/span><\/p>\n<table class=\"wp-block-table w-100\" border=\"1\" cellspacing=\"0\" cellpadding=\"0\">\n<tbody>\n<tr>\n<td style=\"text-align: center; width: 132px;\" valign=\"top\"><span style=\"font-size: medium;\"><strong>MEDICAMENT<\/strong><\/span><\/td>\n<td style=\"text-align: center; width: 75px;\" valign=\"top\"><span style=\"font-size: medium;\"><strong>\u0423<sub>1\/2<\/sub><\/strong><strong>\u00a0<\/strong><\/span><\/td>\n<td style=\"text-align: center; width: 90px;\" valign=\"top\"><span style=\"font-size: medium;\"><strong>T p\u00e2n\u0103 la steady state<\/strong><\/span><\/td>\n<td style=\"text-align: center; width: 60px;\" valign=\"top\"><span style=\"font-size: medium;\"><strong>Tip prob\u0103<\/strong><\/span><\/td>\n<td style=\"text-align: center; width: 124px;\" valign=\"top\"><span style=\"font-size: medium;\"><strong>Stabilitate prob\u0103<\/strong><\/span><\/td>\n<td style=\"text-align: center; width: 113px;\" valign=\"top\"><span style=\"font-size: medium;\"><strong>Metod\u0103 de determinare<\/strong><\/span><\/td>\n<td style=\"text-align: center; width: 128px;\" valign=\"top\"><span style=\"font-size: medium;\"><strong>Interval terapeutic<\/strong><\/span><\/td>\n<\/tr>\n<tr>\n<td style=\"text-align: left; width: 132px;\" valign=\"top\"><span style=\"font-size: medium;\">\u0414\u0438\u0433\u043e\u043a\u0441\u0438\u043d<\/span><\/td>\n<td style=\"text-align: center; width: 75px;\" valign=\"top\"><span style=\"font-size: medium;\">36-48 h<\/span><\/td>\n<td style=\"text-align: center; width: 90px;\" valign=\"top\"><span style=\"font-size: medium;\">7-10 zile<\/span><\/td>\n<td style=\"text-align: center; width: 60px;\" valign=\"top\"><span style=\"font-size: medium;\">\u0421\u044b\u0432\u043e\u0440\u043e\u0442\u043a\u0430<\/span><\/td>\n<td style=\"text-align: center; width: 124px;\" valign=\"top\"><span style=\"font-size: medium;\">7 zile<\/span><\/p>\n<p style=\"text-align: center;\"><span style=\"font-size: medium;\">la 2-8\u00b0C<\/span><\/p>\n<\/td>\n<td style=\"text-align: center; width: 113px;\" valign=\"top\"><span style=\"font-size: medium;\">ECLIA<\/span><\/td>\n<td style=\"text-align: center; width: 128px;\" valign=\"top\"><span style=\"font-size: medium;\">0.9-2 ng\/mL<\/span><\/td>\n<\/tr>\n<tr>\n<td style=\"text-align: left; width: 132px;\" valign=\"top\"><span style=\"font-size: medium;\">Amiodarona<\/span><\/td>\n<td style=\"text-align: center; width: 75px;\" valign=\"top\"><span style=\"font-size: medium;\">26-107 zile<\/span><\/td>\n<td style=\"text-align: center; width: 90px;\" valign=\"top\"><span style=\"font-size: medium;\">Nu se aplica<\/span><\/td>\n<td style=\"text-align: center; width: 60px;\" valign=\"top\"><span style=\"font-size: medium;\">\u0421\u044b\u0432\u043e\u0440\u043e\u0442\u043a\u0430<\/span><\/td>\n<td style=\"text-align: center; width: 124px;\" valign=\"top\"><span style=\"font-size: medium;\">7 zile<\/span><\/p>\n<p style=\"text-align: center;\"><span style=\"font-size: medium;\">la 2-8\u00b0C<\/span><\/p>\n<\/td>\n<td style=\"text-align: center; width: 113px;\" valign=\"top\"><span style=\"font-size: medium;\">HPLC<\/span><\/td>\n<td style=\"text-align: center; width: 128px;\" valign=\"top\"><span style=\"font-size: medium;\">0.5-2 mg\/L<\/span><\/td>\n<\/tr>\n<tr>\n<td style=\"text-align: left; width: 132px;\" valign=\"top\"><span style=\"font-size: medium;\">Flecainida<\/span><\/td>\n<td style=\"text-align: center; width: 75px;\" valign=\"top\"><span style=\"font-size: medium;\">12-27 ore<\/span><\/td>\n<td style=\"text-align: center; width: 90px;\" valign=\"top\"><span style=\"font-size: medium;\">3-6 zile<\/span><\/td>\n<td style=\"text-align: center; width: 60px;\" valign=\"top\"><span style=\"font-size: medium;\">\u0421\u044b\u0432\u043e\u0440\u043e\u0442\u043a\u0430<\/span><\/td>\n<td style=\"text-align: center; width: 124px;\" valign=\"top\"><span style=\"font-size: medium;\">7 zile la 2-8\u00b0C<\/span><\/td>\n<td style=\"text-align: center; width: 113px;\" valign=\"top\"><span style=\"font-size: medium;\">HPLC<\/span><\/td>\n<td style=\"text-align: center; width: 128px;\" valign=\"top\"><span style=\"font-size: medium;\">0.2-0.8 mg\/L<\/span><\/td>\n<\/tr>\n<tr>\n<td style=\"text-align: left; width: 132px;\" valign=\"top\"><span style=\"font-size: medium;\">Teofilina<\/span><\/td>\n<td style=\"text-align: center; width: 75px;\" valign=\"top\"><span style=\"font-size: medium;\">7-11 ore (adult);\u00a0\u00a0\u00a01-8 ore (copil)<\/span><\/td>\n<td style=\"text-align: center; width: 90px;\" valign=\"top\"><span style=\"font-size: medium;\">15-55 ore (adult);\u00a0\u00a0\u00a05-40 ore (copil)<\/span><\/td>\n<td style=\"text-align: center; width: 60px;\" valign=\"top\"><span style=\"font-size: medium;\">\u0421\u044b\u0432\u043e\u0440\u043e\u0442\u043a\u0430<\/span><\/td>\n<td style=\"text-align: center; width: 124px;\" valign=\"top\"><span style=\"font-size: medium;\">7 zile la 2-8\u00b0C<\/span><\/td>\n<td style=\"text-align: center; width: 113px;\" valign=\"top\"><span style=\"font-size: medium;\">HPLC<\/span><\/td>\n<td style=\"text-align: center; width: 128px;\" valign=\"top\"><span style=\"font-size: medium;\">&lt; 1 an:5-10 mg\/L\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0<\/span><span style=\"font-size: medium;\">\u2265 1 an:\u00a0\u00a0\u00a08-20 mg\/L<\/span><\/td>\n<\/tr>\n<tr>\n<td style=\"text-align: left; width: 132px;\" valign=\"top\"><span style=\"font-size: medium;\">\u0412\u0430\u043d\u043a\u043e\u043c\u0438\u0446\u0438\u043d<\/span><\/td>\n<td style=\"width: 75px;\" valign=\"top\">\n<p style=\"text-align: center;\"><span style=\"font-size: medium;\">3-8 ore<\/span><\/p>\n<\/td>\n<td style=\"width: 90px;\" valign=\"top\">\n<p style=\"text-align: center;\"><span style=\"font-size: medium;\">1-2 zile<\/span><\/p>\n<\/td>\n<td style=\"width: 60px;\" valign=\"top\">\n<p style=\"text-align: center;\"><span style=\"font-size: medium;\">\u0421\u044b\u0432\u043e\u0440\u043e\u0442\u043a\u0430<\/span><\/p>\n<\/td>\n<td style=\"width: 124px;\" valign=\"top\">\n<p style=\"text-align: center;\"><span style=\"font-size: medium;\">7 zile<\/span><\/p>\n<p style=\"text-align: center;\"><span style=\"font-size: medium;\">la 2-8\u00b0C<\/span><\/p>\n<\/td>\n<td style=\"width: 113px;\" valign=\"top\">\n<p style=\"text-align: center;\"><span style=\"font-size: medium;\">FPIA<\/span><\/p>\n<\/td>\n<td style=\"width: 128px;\" valign=\"top\">\n<p style=\"text-align: center;\"><span style=\"font-size: medium;\">5 \u2013 10 \u00b5g\/mL<\/span><\/p>\n<p style=\"text-align: center;\"><span style=\"font-size: medium;\">\u00a0<\/span><\/p>\n<\/td>\n<\/tr>\n<tr>\n<td style=\"text-align: left; width: 132px;\" valign=\"top\"><span style=\"font-size: medium;\">Carbamazepin<\/span><\/td>\n<td style=\"width: 75px;\" valign=\"top\">\n<p style=\"text-align: center;\"><span style=\"font-size: medium;\">14-47 ore (adult);<\/span><\/p>\n<p style=\"text-align: center;\"><span style=\"font-size: medium;\">8-19 ore (copil)<\/span><\/p>\n<\/td>\n<td style=\"width: 90px;\" valign=\"top\">\n<p style=\"text-align: center;\"><span style=\"font-size: medium;\">7-12 zile (adult);<\/span><\/p>\n<p style=\"text-align: center;\"><span style=\"font-size: medium;\">2-4 zile (copil)<\/span><\/p>\n<\/td>\n<td style=\"width: 60px;\" valign=\"top\">\n<p style=\"text-align: center;\"><span style=\"font-size: medium;\">\u0421\u044b\u0432\u043e\u0440\u043e\u0442\u043a\u0430<\/span><\/p>\n<\/td>\n<td style=\"width: 124px;\" valign=\"top\">\n<p style=\"text-align: center;\"><span style=\"font-size: medium;\">7 zile<\/span><\/p>\n<p style=\"text-align: center;\"><span style=\"font-size: medium;\">la 2-8\u00b0C<\/span><\/p>\n<\/td>\n<td style=\"width: 113px;\" valign=\"top\">\n<p style=\"text-align: center;\"><span style=\"font-size: medium;\">HPLC<\/span><\/p>\n<\/td>\n<td style=\"width: 128px;\" valign=\"top\">\n<p style=\"text-align: center;\"><span style=\"font-size: medium;\">4-10 mg\/L<\/span><\/p>\n<\/td>\n<\/tr>\n<tr>\n<td style=\"text-align: left; width: 132px;\" valign=\"top\"><span style=\"font-size: medium;\">\u0412\u0430\u043b\u044c\u043f\u0440\u043e\u0435\u0432\u0430\u044f \u043a\u0438\u0441\u043b\u043e\u0442\u0430<\/span><\/td>\n<td style=\"width: 75px;\" valign=\"top\">\n<p style=\"text-align: center;\"><span style=\"font-size: medium;\">9-16 ore (adult);<\/span><\/p>\n<p style=\"text-align: center;\"><span style=\"font-size: medium;\">7-13 ore (copil)<\/span><\/p>\n<\/td>\n<td style=\"width: 90px;\" valign=\"top\">\n<p style=\"text-align: center;\"><span style=\"font-size: medium;\">2-4 zile (adult);<\/span><\/p>\n<p style=\"text-align: center;\"><span style=\"font-size: medium;\">2-4 zile (copil)<\/span><\/p>\n<\/td>\n<td style=\"width: 60px;\" valign=\"top\">\n<p style=\"text-align: center;\"><span style=\"font-size: medium;\">\u0421\u044b\u0432\u043e\u0440\u043e\u0442\u043a\u0430<\/span><\/p>\n<\/td>\n<td style=\"width: 124px;\" valign=\"top\">\n<p style=\"text-align: center;\"><span style=\"font-size: medium;\">7 zile<\/span><\/p>\n<p style=\"text-align: center;\"><span style=\"font-size: medium;\">la 2-8\u00b0C<\/span><\/p>\n<\/td>\n<td style=\"width: 113px;\" valign=\"top\">\n<p style=\"text-align: center;\"><span style=\"font-size: medium;\">CEDIA<\/span><\/p>\n<\/td>\n<td style=\"width: 128px;\" valign=\"top\">\n<p style=\"text-align: center;\"><span style=\"font-size: medium;\">50-100 mg\/L<\/span><\/p>\n<\/td>\n<\/tr>\n<tr>\n<td style=\"text-align: left; width: 132px;\" valign=\"top\"><span style=\"font-size: medium;\">\u0422\u043e\u043f\u0438\u0440\u0430\u043c\u0430\u0442<\/span><\/td>\n<td style=\"width: 75px;\" valign=\"top\">\n<p style=\"text-align: center;\"><span style=\"font-size: medium;\">19-23 ore<\/span><\/p>\n<\/td>\n<td style=\"width: 90px;\" valign=\"top\">\n<p style=\"text-align: center;\"><span style=\"font-size: medium;\">5 zile<\/span><\/p>\n<\/td>\n<td style=\"width: 60px;\" valign=\"top\">\n<p style=\"text-align: center;\"><span style=\"font-size: medium;\">\u0421\u044b\u0432\u043e\u0440\u043e\u0442\u043a\u0430<\/span><\/p>\n<\/td>\n<td style=\"width: 124px;\" valign=\"top\">\n<p style=\"text-align: center;\"><span style=\"font-size: medium;\">7 zile<\/span><\/p>\n<p style=\"text-align: center;\"><span style=\"font-size: medium;\">la 2-8\u00b0C<\/span><\/p>\n<\/td>\n<td style=\"width: 113px;\" valign=\"top\">\n<p style=\"text-align: center;\"><span style=\"font-size: medium;\">HPLC<\/span><\/p>\n<\/td>\n<td style=\"width: 128px;\" valign=\"top\">\n<p style=\"text-align: center;\"><span style=\"font-size: medium;\">1-10 mg\/L<\/span><\/p>\n<\/td>\n<\/tr>\n<tr>\n<td style=\"text-align: left; width: 132px;\" valign=\"top\"><span style=\"font-size: medium;\">Etosuximid<\/span><\/td>\n<td style=\"width: 75px;\" valign=\"top\">\n<p style=\"text-align: center;\"><span style=\"font-size: medium;\">50-60 ore (adult);<\/span><\/p>\n<p style=\"text-align: center;\"><span style=\"font-size: medium;\">30 ore (copil)<\/span><\/p>\n<\/td>\n<td style=\"width: 90px;\" valign=\"top\">\n<p style=\"text-align: center;\"><span style=\"font-size: medium;\">8-12 zile (adult);<\/span><\/p>\n<p style=\"text-align: center;\"><span style=\"font-size: medium;\">6-10 zile (copil)<\/span><\/p>\n<\/td>\n<td style=\"width: 60px;\" valign=\"top\">\n<p style=\"text-align: center;\"><span style=\"font-size: medium;\">\u0421\u044b\u0432\u043e\u0440\u043e\u0442\u043a\u0430<\/span><\/p>\n<\/td>\n<td style=\"width: 124px;\" valign=\"top\">\n<p style=\"text-align: center;\"><span style=\"font-size: medium;\">7 zile<\/span><\/p>\n<p style=\"text-align: center;\"><span style=\"font-size: medium;\">la 2-8\u00b0C<\/span><\/p>\n<\/td>\n<td style=\"width: 113px;\" valign=\"top\">\n<p style=\"text-align: center;\"><span style=\"font-size: medium;\">HPLC<\/span><\/p>\n<\/td>\n<td style=\"width: 128px;\" valign=\"top\">\n<p style=\"text-align: center;\"><span style=\"font-size: medium;\">40-100 mg\/L<\/span><\/p>\n<\/td>\n<\/tr>\n<tr>\n<td style=\"text-align: left; width: 132px;\" valign=\"top\"><span style=\"font-size: medium;\">\u0424\u0435\u043d\u043e\u0431\u0430\u0440\u0431\u0438\u0442\u0430\u043b<\/span><\/td>\n<td style=\"width: 75px;\" valign=\"top\">\n<p style=\"text-align: center;\"><span style=\"font-size: medium;\">81-117 ore (adult);<\/span><\/p>\n<p style=\"text-align: center;\"><span style=\"font-size: medium;\">40-70 ore (copil)<\/span><\/p>\n<\/td>\n<td style=\"width: 90px;\" valign=\"top\">\n<p style=\"text-align: center;\"><span style=\"font-size: medium;\">17-24 zile (adult);<\/span><\/p>\n<p style=\"text-align: center;\"><span style=\"font-size: medium;\">8-15 zile (copil)<\/span><\/p>\n<\/td>\n<td style=\"width: 60px;\" valign=\"top\">\n<p style=\"text-align: center;\"><span style=\"font-size: medium;\">\u0421\u044b\u0432\u043e\u0440\u043e\u0442\u043a\u0430<\/span><\/p>\n<\/td>\n<td style=\"width: 124px;\" valign=\"top\">\n<p style=\"text-align: center;\"><span style=\"font-size: medium;\">7 zile<\/span><\/p>\n<p style=\"text-align: center;\"><span style=\"font-size: medium;\">la 2-8\u00b0C<\/span><\/p>\n<\/td>\n<td style=\"width: 113px;\" valign=\"top\">\n<p style=\"text-align: center;\"><span style=\"font-size: medium;\">HPLC<\/span><\/p>\n<\/td>\n<td style=\"width: 128px;\" valign=\"top\">\n<p style=\"text-align: center;\"><span style=\"font-size: medium;\">10-40 mg\/L<\/span><\/p>\n<\/td>\n<\/tr>\n<tr>\n<td style=\"text-align: left; width: 132px;\" valign=\"top\"><span style=\"font-size: medium;\">\u0424\u0435\u043d\u0438\u0442\u043e\u0438\u043d<\/span><\/td>\n<td style=\"width: 75px;\" valign=\"top\">\n<p style=\"text-align: center;\"><span style=\"font-size: medium;\">18-22 ore (adult);<\/span><\/p>\n<p style=\"text-align: center;\"><span style=\"font-size: medium;\">7-29 ore (copil)<\/span><\/p>\n<\/td>\n<td style=\"width: 90px;\" valign=\"top\">\n<p style=\"text-align: center;\"><span style=\"font-size: medium;\">4-8 zile (adult);<\/span><\/p>\n<p style=\"text-align: center;\"><span style=\"font-size: medium;\">2-5 zile (copil)<\/span><\/p>\n<\/td>\n<td style=\"width: 60px;\" valign=\"top\"><span style=\"font-size: medium;\">\u0421\u044b\u0432\u043e\u0440\u043e\u0442\u043a\u0430<\/span><\/td>\n<td style=\"width: 124px;\" valign=\"top\">\n<p style=\"text-align: center;\"><span style=\"font-size: medium;\">7 zile<\/span><\/p>\n<p style=\"text-align: center;\"><span style=\"font-size: medium;\">la 2-8\u00b0C<\/span><\/p>\n<\/td>\n<td style=\"width: 113px;\" valign=\"top\">\n<p style=\"text-align: center;\"><span style=\"font-size: medium;\">HPLC<\/span><\/p>\n<\/td>\n<td style=\"width: 128px;\" valign=\"top\">\n<p style=\"text-align: center;\"><span style=\"font-size: medium;\">&lt;14 ani:<\/span><\/p>\n<p style=\"text-align: center;\"><span style=\"font-size: medium;\">10-20 mg\/L<\/span><\/p>\n<p style=\"text-align: center;\"><span style=\"font-size: medium;\">&gt;14 ani:<\/span><\/p>\n<p style=\"text-align: center;\"><span style=\"font-size: medium;\">6-14 mg\/L<\/span><\/p>\n<\/td>\n<\/tr>\n<tr>\n<td style=\"text-align: left; width: 132px;\" valign=\"top\"><span style=\"font-size: medium;\">\u0413\u0430\u0431\u0430\u043f\u0435\u043d\u0442\u0438\u043d<\/span><\/td>\n<td style=\"width: 75px;\" valign=\"top\">\n<p style=\"text-align: center;\"><span style=\"font-size: medium;\">5-7 ore (adult);<\/span><\/p>\n<p style=\"text-align: center;\"><span style=\"font-size: medium;\">4-6 ore (copil)<\/span><\/p>\n<\/td>\n<td style=\"width: 90px;\" valign=\"top\">\n<p style=\"text-align: center;\"><span style=\"font-size: medium;\">1-2 zile (adult);<\/span><\/p>\n<p style=\"text-align: center;\"><span style=\"font-size: medium;\">1-2 zile (copil)<\/span><\/p>\n<\/td>\n<td style=\"width: 60px;\" valign=\"top\">\n<p style=\"text-align: center;\"><span style=\"font-size: medium;\">\u0421\u044b\u0432\u043e\u0440\u043e\u0442\u043a\u0430<\/span><\/p>\n<\/td>\n<td style=\"width: 124px;\" valign=\"top\">\n<p style=\"text-align: center;\"><span style=\"font-size: medium;\">7 zile<\/span><\/p>\n<p style=\"text-align: center;\"><span style=\"font-size: medium;\">la 2-8\u00b0C<\/span><\/p>\n<\/td>\n<td style=\"width: 113px;\" valign=\"top\">\n<p style=\"text-align: center;\"><span style=\"font-size: medium;\">HPLC<\/span><\/p>\n<\/td>\n<td style=\"width: 128px;\" valign=\"top\">\n<p style=\"text-align: center;\"><span style=\"font-size: medium;\">2 \u2013 10 \u00b5g\/mL<\/span><\/p>\n<\/td>\n<\/tr>\n<tr>\n<td style=\"text-align: left; width: 132px;\" valign=\"top\"><span style=\"font-size: medium;\">\u041b\u0430\u043c\u043e\u0442\u0440\u0438\u0434\u0436\u0438\u043d<\/span><\/td>\n<td style=\"width: 75px;\" valign=\"top\">\n<p style=\"text-align: center;\"><span style=\"font-size: medium;\">15-30 ore (adult);<\/span><\/p>\n<p style=\"text-align: center;\"><span style=\"font-size: medium;\">30 ore (copil)<\/span><\/p>\n<\/td>\n<td style=\"width: 90px;\" valign=\"top\">\n<p style=\"text-align: center;\"><span style=\"font-size: medium;\">3-10 zile (adult);<\/span><\/p>\n<p style=\"text-align: center;\"><span style=\"font-size: medium;\">3-10 zile (copil)<\/span><\/p>\n<\/td>\n<td style=\"width: 60px;\" valign=\"top\">\n<p style=\"text-align: center;\"><span style=\"font-size: medium;\">\u0421\u044b\u0432\u043e\u0440\u043e\u0442\u043a\u0430<\/span><\/p>\n<\/td>\n<td style=\"width: 124px;\" valign=\"top\">\n<p style=\"text-align: center;\"><span style=\"font-size: medium;\">7 zile<\/span><\/p>\n<p style=\"text-align: center;\"><span style=\"font-size: medium;\">la 2-8\u00b0C<\/span><\/p>\n<\/td>\n<td style=\"width: 113px;\" valign=\"top\">\n<p style=\"text-align: center;\"><span style=\"font-size: medium;\">HPLC<\/span><\/p>\n<\/td>\n<td style=\"width: 128px;\" valign=\"top\">\n<p style=\"text-align: center;\"><span style=\"font-size: medium;\">&lt;14 ani:<\/span><\/p>\n<p style=\"text-align: center;\"><span style=\"font-size: medium;\">5-15 mg\/L<\/span><\/p>\n<p style=\"text-align: center;\"><span style=\"font-size: medium;\">&gt;14 ani:<\/span><\/p>\n<p style=\"text-align: center;\"><span style=\"font-size: medium;\">1-5 mg\/L<\/span><\/p>\n<\/td>\n<\/tr>\n<tr>\n<td style=\"text-align: left; width: 132px;\" valign=\"top\"><span style=\"font-size: medium;\">\u041f\u0440\u0438\u043c\u0438\u0434\u043e\u043d<\/span><\/td>\n<td style=\"width: 75px;\" valign=\"top\">\n<p style=\"text-align: center;\"><span style=\"font-size: medium;\">3-7 ore (adult);<\/span><\/p>\n<p style=\"text-align: center;\"><span style=\"font-size: medium;\">4-6 ore (copil)<\/span><\/p>\n<\/td>\n<td style=\"width: 90px;\" valign=\"top\">\n<p style=\"text-align: center;\"><span style=\"font-size: medium;\">16-60 ore (adult);<\/span><\/p>\n<p style=\"text-align: center;\"><span style=\"font-size: medium;\">20-30 ore (copil)<\/span><\/p>\n<\/td>\n<td style=\"width: 60px;\" valign=\"top\">\n<p style=\"text-align: center;\"><span style=\"font-size: medium;\">\u0421\u044b\u0432\u043e\u0440\u043e\u0442\u043a\u0430<\/span><\/p>\n<\/td>\n<td style=\"width: 124px;\" valign=\"top\">\n<p style=\"text-align: center;\"><span style=\"font-size: medium;\">7 zile<\/span><\/p>\n<p style=\"text-align: center;\"><span style=\"font-size: medium;\">la 2-8\u00b0C<\/span><\/p>\n<\/td>\n<td style=\"width: 113px;\" valign=\"top\">\n<p style=\"text-align: center;\"><span style=\"font-size: medium;\">HPLC<\/span><\/p>\n<\/td>\n<td style=\"width: 128px;\" valign=\"top\">\n<p style=\"text-align: center;\"><span style=\"font-size: medium;\">5-15 mg\/L<\/span><\/p>\n<\/td>\n<\/tr>\n<tr>\n<td style=\"text-align: left; width: 132px;\" valign=\"top\"><span style=\"font-size: medium;\">Amitriptilina<\/span><\/td>\n<td style=\"width: 75px;\" valign=\"top\">\n<p style=\"text-align: center;\"><span style=\"font-size: medium;\">8-51 ore<\/span><\/p>\n<\/td>\n<td style=\"width: 90px;\" valign=\"top\">\n<p style=\"text-align: center;\"><span style=\"font-size: medium;\">2-6 zile<\/span><\/p>\n<\/td>\n<td style=\"width: 60px;\" valign=\"top\">\n<p style=\"text-align: center;\"><span style=\"font-size: medium;\">\u0421\u044b\u0432\u043e\u0440\u043e\u0442\u043a\u0430<\/span><\/p>\n<\/td>\n<td style=\"width: 124px;\" valign=\"top\">\n<p style=\"text-align: center;\"><span style=\"font-size: medium;\">7 zile la 2-8\u00b0C<\/span><\/p>\n<\/td>\n<td style=\"width: 113px;\" valign=\"top\">\n<p style=\"text-align: center;\"><span style=\"font-size: medium;\">LC-MS\/MS<\/span><\/p>\n<\/td>\n<td style=\"width: 128px;\" valign=\"top\">\n<p style=\"text-align: center;\"><span style=\"font-size: medium;\">50-300 \u00b5g\/L<\/span><\/p>\n<\/td>\n<\/tr>\n<tr>\n<td style=\"text-align: left; width: 132px;\" valign=\"top\"><span style=\"font-size: medium;\">\u041b\u0438\u0442\u0438\u0439<\/span><\/td>\n<td style=\"width: 75px;\" valign=\"top\">\n<p style=\"text-align: center;\"><span style=\"font-size: medium;\">14-30 ore<\/span><\/p>\n<\/td>\n<td style=\"width: 90px;\" valign=\"top\">\n<p style=\"text-align: center;\"><span style=\"font-size: medium;\">2-7 zile<\/span><\/p>\n<\/td>\n<td style=\"width: 60px;\" valign=\"top\">\n<p style=\"text-align: center;\"><span style=\"font-size: medium;\">\u0421\u044b\u0432\u043e\u0440\u043e\u0442\u043a\u0430<\/span><\/p>\n<\/td>\n<td style=\"width: 124px;\" valign=\"top\">\n<p style=\"text-align: center;\"><span style=\"font-size: medium;\"><em>8 ore<\/em> la temperatura camerei; <\/span><\/p>\n<p style=\"text-align: center;\"><span style=\"font-size: medium;\"><em>24 ore<\/em> la 2-8\u00b0C; <em>6 luni<\/em> la -18\u00b0C<\/span><\/p>\n<\/td>\n<td style=\"width: 113px;\" valign=\"top\">\n<p style=\"text-align: center;\"><span style=\"font-size: medium;\">ISE<\/span><\/p>\n<\/td>\n<td style=\"width: 128px;\" valign=\"top\">\n<p style=\"text-align: center;\"><span style=\"font-size: medium;\">Mania acuta: 0.6-1.2 mmol\/L<\/span><\/p>\n<p style=\"text-align: center;\"><span style=\"font-size: medium;\">\u2022 Protec\u0163ie impotriva viitoarelor episoade la pacien\u0163ii cu afec\u0163iune bipolara: 0.8-1.0 mmol\/L<\/span><\/p>\n<p style=\"text-align: center;\"><span style=\"font-size: medium;\">\u2022 Depresie: 0.5- 1.5 mmol\/L<\/span><\/p>\n<\/td>\n<\/tr>\n<tr>\n<td style=\"text-align: left; width: 132px;\" valign=\"top\"><span style=\"font-size: medium;\">Clomipramin<\/span><\/td>\n<td style=\"width: 75px;\" valign=\"top\">\n<p style=\"text-align: center;\"><span style=\"font-size: medium;\">12-36 ore<\/span><\/p>\n<\/td>\n<td style=\"width: 90px;\" valign=\"top\">\n<p style=\"text-align: center;\"><span style=\"font-size: medium;\">3 saptamani<\/span><\/p>\n<\/td>\n<td style=\"width: 60px;\" valign=\"top\">\n<p style=\"text-align: center;\"><span style=\"font-size: medium;\">\u0421\u044b\u0432\u043e\u0440\u043e\u0442\u043a\u0430<\/span><\/p>\n<\/td>\n<td style=\"width: 124px;\" valign=\"top\">\n<p style=\"text-align: center;\"><span style=\"font-size: medium;\">7 zile<\/span><\/p>\n<p style=\"text-align: center;\"><span style=\"font-size: medium;\">la 2-8\u00b0C<\/span><\/p>\n<\/td>\n<td style=\"width: 113px;\" valign=\"top\">\n<p style=\"text-align: center;\"><span style=\"font-size: medium;\">LC-MS\/MS<\/span><\/p>\n<\/td>\n<td style=\"width: 128px;\" valign=\"top\">\n<p style=\"text-align: center;\"><span style=\"font-size: medium;\">90-250 \u00b5g\/L<\/span><\/p>\n<\/td>\n<\/tr>\n<tr>\n<td style=\"text-align: left; width: 132px;\" valign=\"top\"><span style=\"font-size: medium;\">Clozapina<\/span><\/td>\n<td style=\"width: 75px;\" valign=\"top\">\n<p style=\"text-align: center;\"><span style=\"font-size: medium;\">4-66 ore<\/span><\/p>\n<\/td>\n<td style=\"width: 90px;\" valign=\"top\">\n<p style=\"text-align: center;\"><span style=\"font-size: medium;\">Nu se aplica<\/span><\/p>\n<\/td>\n<td style=\"width: 60px;\" valign=\"top\">\n<p style=\"text-align: center;\"><span style=\"font-size: medium;\">\u0421\u044b\u0432\u043e\u0440\u043e\u0442\u043a\u0430<\/span><\/p>\n<\/td>\n<td style=\"width: 124px;\" valign=\"top\">\n<p style=\"text-align: center;\"><span style=\"font-size: medium;\">7 zile<\/span><\/p>\n<p style=\"text-align: center;\"><span style=\"font-size: medium;\">la 2-8\u00b0C<\/span><\/p>\n<\/td>\n<td style=\"width: 113px;\" valign=\"top\">\n<p style=\"text-align: center;\"><span style=\"font-size: medium;\">LC-MS\/MS<\/span><\/p>\n<\/td>\n<td style=\"width: 128px;\" valign=\"top\">\n<p style=\"text-align: center;\"><span style=\"font-size: medium;\">350-600 \u00b5g\/L<\/span><\/p>\n<\/td>\n<\/tr>\n<tr>\n<td style=\"text-align: left; width: 132px;\" valign=\"top\"><span style=\"font-size: medium;\">Olanzapin<\/span><\/td>\n<td style=\"width: 75px;\" valign=\"top\">\n<p style=\"text-align: center;\"><span style=\"font-size: medium;\">21-54 ore (adult \u226465 ani);<\/span><\/p>\n<p style=\"text-align: center;\"><span style=\"font-size: medium;\">32-81 ore (adult &gt;65 ani)<\/span><\/p>\n<\/td>\n<td style=\"width: 90px;\" valign=\"top\">\n<p style=\"text-align: center;\"><span style=\"font-size: medium;\">7 zile<\/span><\/p>\n<\/td>\n<td style=\"width: 60px;\" valign=\"top\">\n<p style=\"text-align: center;\"><span style=\"font-size: medium;\">\u0421\u044b\u0432\u043e\u0440\u043e\u0442\u043a\u0430<\/span><\/p>\n<\/td>\n<td style=\"width: 124px;\" valign=\"top\">\n<p style=\"text-align: center;\"><span style=\"font-size: medium;\">7 zile<\/span><\/p>\n<p style=\"text-align: center;\"><span style=\"font-size: medium;\">la 2-8\u00b0C<\/span><\/p>\n<\/td>\n<td style=\"width: 113px;\" valign=\"top\">\n<p style=\"text-align: center;\"><span style=\"font-size: medium;\">LC-MS\/MS<\/span><\/p>\n<\/td>\n<td style=\"width: 128px;\" valign=\"top\">\n<p style=\"text-align: center;\"><span style=\"font-size: medium;\">\u00a010-80 \u00b5g\/L<\/span><\/p>\n<\/td>\n<\/tr>\n<tr>\n<td style=\"text-align: left; width: 132px;\" valign=\"top\"><span style=\"font-size: medium;\">Doxepin<\/span><\/td>\n<td style=\"width: 75px;\" valign=\"top\">\n<p style=\"text-align: center;\"><span style=\"font-size: medium;\">8-25 ore<\/span><\/p>\n<\/td>\n<td style=\"width: 90px;\" valign=\"top\">\n<p style=\"text-align: center;\"><span style=\"font-size: medium;\">2.5-5 zile<\/span><\/p>\n<\/td>\n<td style=\"width: 60px;\" valign=\"top\">\n<p style=\"text-align: center;\"><span style=\"font-size: medium;\">\u0421\u044b\u0432\u043e\u0440\u043e\u0442\u043a\u0430<\/span><\/p>\n<\/td>\n<td style=\"width: 124px;\" valign=\"top\">\n<p style=\"text-align: center;\"><span style=\"font-size: medium;\">7 zile<\/span><\/p>\n<p style=\"text-align: center;\"><span style=\"font-size: medium;\">la 2-8\u00b0C<\/span><\/p>\n<\/td>\n<td style=\"width: 113px;\" valign=\"top\">\n<p style=\"text-align: center;\"><span style=\"font-size: medium;\">LC-MS\/MS<\/span><\/p>\n<\/td>\n<td style=\"width: 128px;\" valign=\"top\">\n<p style=\"text-align: center;\"><span style=\"font-size: medium;\">20-150 \u00b5g\/L<\/span><\/p>\n<\/td>\n<\/tr>\n<tr>\n<td style=\"text-align: left; width: 132px;\" valign=\"top\"><span style=\"font-size: medium;\">Imipramin<\/span><\/td>\n<td style=\"width: 75px;\" valign=\"top\">\n<p style=\"text-align: center;\"><span style=\"font-size: medium;\">6-20 ore<\/span><\/p>\n<\/td>\n<td style=\"width: 90px;\" valign=\"top\">\n<p style=\"text-align: center;\"><span style=\"font-size: medium;\">2-5 zile<\/span><\/p>\n<\/td>\n<td style=\"width: 60px;\" valign=\"top\">\n<p style=\"text-align: center;\"><span style=\"font-size: medium;\">\u0421\u044b\u0432\u043e\u0440\u043e\u0442\u043a\u0430<\/span><\/p>\n<\/td>\n<td style=\"width: 124px;\" valign=\"top\">\n<p style=\"text-align: center;\"><span style=\"font-size: medium;\">7 zile<\/span><\/p>\n<p style=\"text-align: center;\"><span style=\"font-size: medium;\">la 2-8\u00b0C<\/span><\/p>\n<\/td>\n<td style=\"width: 113px;\" valign=\"top\">\n<p style=\"text-align: center;\"><span style=\"font-size: medium;\">LC-MS\/MS<\/span><\/p>\n<\/td>\n<td style=\"width: 128px;\" valign=\"top\">\n<p style=\"text-align: center;\"><span style=\"font-size: medium;\">45-150 \u00b5g\/L<\/span><\/p>\n<\/td>\n<\/tr>\n<tr>\n<td style=\"text-align: left; width: 132px;\" valign=\"top\"><span style=\"font-size: medium;\">Maprotilin<\/span><\/td>\n<td style=\"width: 75px;\" valign=\"top\">\n<p style=\"text-align: center;\"><span style=\"font-size: medium;\">36-105 ore<\/span><\/p>\n<\/td>\n<td style=\"width: 90px;\" valign=\"top\">\n<p style=\"text-align: center;\"><span style=\"font-size: medium;\">14 zile<\/span><\/p>\n<\/td>\n<td style=\"width: 60px;\" valign=\"top\">\n<p style=\"text-align: center;\"><span style=\"font-size: medium;\">\u0421\u044b\u0432\u043e\u0440\u043e\u0442\u043a\u0430<\/span><\/p>\n<\/td>\n<td style=\"width: 124px;\" valign=\"top\">\n<p style=\"text-align: center;\"><span style=\"font-size: medium;\">7 zile<\/span><\/p>\n<p style=\"text-align: center;\"><span style=\"font-size: medium;\">la 2-8\u00b0C<\/span><\/p>\n<\/td>\n<td style=\"width: 113px;\" valign=\"top\">\n<p style=\"text-align: center;\"><span style=\"font-size: medium;\">LC-MS\/MS<\/span><\/p>\n<\/td>\n<td style=\"width: 128px;\" valign=\"top\">\n<p style=\"text-align: center;\"><span style=\"font-size: medium;\">125-200 \u00b5g\/L<\/span><\/p>\n<\/td>\n<\/tr>\n<tr>\n<td style=\"text-align: left; width: 132px;\" valign=\"top\"><span style=\"font-size: medium;\">Trimipramin<\/span><\/td>\n<td style=\"width: 75px;\" valign=\"top\">\n<p style=\"text-align: center;\"><span style=\"font-size: medium;\">16-39 ore<\/span><\/p>\n<\/td>\n<td style=\"width: 90px;\" valign=\"top\">\n<p style=\"text-align: center;\"><span style=\"font-size: medium;\">Nu se aplica<\/span><\/p>\n<\/td>\n<td style=\"width: 60px;\" valign=\"top\">\n<p style=\"text-align: center;\"><span style=\"font-size: medium;\">\u0421\u044b\u0432\u043e\u0440\u043e\u0442\u043a\u0430<\/span><\/p>\n<\/td>\n<td style=\"width: 124px;\" valign=\"top\">\n<p style=\"text-align: center;\"><span style=\"font-size: medium;\">7 zile<\/span><\/p>\n<p style=\"text-align: center;\"><span style=\"font-size: medium;\">la 2-8\u00b0C<\/span><\/p>\n<\/td>\n<td style=\"width: 113px;\" valign=\"top\">\n<p style=\"text-align: center;\"><span style=\"font-size: medium;\">LC-MS\/MS<\/span><\/p>\n<\/td>\n<td style=\"width: 128px;\" valign=\"top\">\n<p style=\"text-align: center;\"><span style=\"font-size: medium;\">150-350 \u00b5g\/L<\/span><\/p>\n<\/td>\n<\/tr>\n<tr>\n<td style=\"text-align: left; width: 132px;\" valign=\"top\"><span style=\"font-size: medium;\">Haloperidol<\/span><\/td>\n<td style=\"width: 75px;\" valign=\"top\">\n<p style=\"text-align: center;\"><span style=\"font-size: medium;\">41-41 ore (lactat);<\/span><\/p>\n<p style=\"text-align: center;\"><span style=\"font-size: medium;\">14-28 zile (decanoat)<\/span><\/p>\n<\/td>\n<td style=\"width: 90px;\" valign=\"top\">\n<p style=\"text-align: center;\"><span style=\"font-size: medium;\">3-9 zile (lactat); nu se aplica<\/span><\/p>\n<\/td>\n<td style=\"width: 60px;\" valign=\"top\">\n<p style=\"text-align: center;\"><span style=\"font-size: medium;\">\u0421\u044b\u0432\u043e\u0440\u043e\u0442\u043a\u0430<\/span><\/p>\n<\/td>\n<td style=\"width: 124px;\" valign=\"top\">\n<p style=\"text-align: center;\"><span style=\"font-size: medium;\">7 zile<\/span><\/p>\n<p style=\"text-align: center;\"><span style=\"font-size: medium;\">la 2-8\u00b0C<\/span><\/p>\n<\/td>\n<td style=\"width: 113px;\" valign=\"top\">\n<p style=\"text-align: center;\"><span style=\"font-size: medium;\">LC-MS\/MS<\/span><\/p>\n<\/td>\n<td style=\"width: 128px;\" valign=\"top\">\n<p style=\"text-align: center;\"><span style=\"font-size: medium;\">5-16 \u00b5g\/L<\/span><\/p>\n<\/td>\n<\/tr>\n<tr>\n<td style=\"text-align: left; width: 132px;\" valign=\"top\"><span style=\"font-size: medium;\">Risperidon<\/span><\/td>\n<td style=\"width: 75px;\" valign=\"top\">\n<div style=\"text-align: center;\"><span style=\"font-size: medium;\">3 ore (fast metabolizer risperidon); <\/span><\/div>\n<div style=\"text-align: center;\"><span style=\"font-size: medium;\">21 ore (fast metabolizer 9-hidroxi-risperidon); <\/span><\/div>\n<div style=\"text-align: center;\"><span style=\"font-size: medium;\">20 ore (slow metabolizer risperidon); <\/span><\/div>\n<div style=\"text-align: center;\"><span style=\"font-size: medium;\">30 ore (slow metabolizer 9-hidroxi-risperidon);<\/span><\/div>\n<\/td>\n<td style=\"width: 90px;\" valign=\"top\">\n<p style=\"text-align: center;\"><span style=\"font-size: medium;\">1 zi (fast metabolizer risperidon); 5-6 zile\u00a0 (fast metabolizer 9-hidroxi-risperidon); 5 zile (slow metabolizer risperidon); nu se aplica (slow metabolizer 9-hidroxi-risperidon).<\/span><\/p>\n<\/td>\n<td style=\"width: 60px;\" valign=\"top\">\n<p style=\"text-align: center;\"><span style=\"font-size: medium;\">\u0421\u044b\u0432\u043e\u0440\u043e\u0442\u043a\u0430<\/span><\/p>\n<\/td>\n<td style=\"text-align: center; width: 124px;\" valign=\"top\"><span style=\"font-size: medium;\">7 zile<\/span><\/p>\n<p style=\"text-align: center;\"><span style=\"font-size: medium;\">la 2-8\u00b0C<\/span><\/p>\n<\/td>\n<td style=\"width: 113px;\" valign=\"top\">\n<p style=\"text-align: center;\"><span style=\"font-size: medium;\">LC-MS\/MS<\/span><\/p>\n<\/td>\n<td style=\"width: 128px;\" valign=\"top\">\n<p style=\"text-align: center;\"><span style=\"font-size: medium;\">10-120 \u00b5g\/L<\/span><\/p>\n<\/td>\n<\/tr>\n<tr>\n<td style=\"text-align: left; width: 132px;\" valign=\"top\"><span style=\"font-size: medium;\"><strong>Ciclosporina A<\/strong><\/span><\/td>\n<td style=\"width: 75px;\" valign=\"top\">\n<p style=\"text-align: center;\"><span style=\"font-size: medium;\"><strong>6-27 ore<\/strong><\/span><\/p>\n<\/td>\n<td style=\"width: 90px;\" valign=\"top\">\n<p style=\"text-align: center;\"><span style=\"font-size: medium;\"><strong>2-6 zile<\/strong><\/span><\/p>\n<\/td>\n<td style=\"width: 60px;\" valign=\"top\">\n<p style=\"text-align: center;\"><span style=\"font-size: medium;\"><strong>S\u00e2nge EDTA<\/strong><\/span><\/p>\n<\/td>\n<td style=\"width: 124px;\" valign=\"top\">\n<p style=\"text-align: center;\"><span style=\"font-size: medium;\"><strong>5 zile<\/strong><\/span><\/p>\n<p style=\"text-align: center;\"><span style=\"font-size: medium;\"><strong>la -20\u00b0C<\/strong><\/span><\/p>\n<\/td>\n<td style=\"width: 113px;\" valign=\"top\">\n<p style=\"text-align: center;\"><span style=\"font-size: medium;\"><strong>LC-MS\/MS<\/strong><\/span><\/p>\n<\/td>\n<td style=\"width: 128px;\" valign=\"top\">\n<p style=\"text-align: center;\"><span style=\"font-size: medium;\"><strong>Intervalul terapeutic variaza \u00een func\u0163ie de tipul transplantului \u015fi perioada de timp de la transplant<\/strong><\/span><\/p>\n<p style=\"text-align: center;\"><span style=\"font-size: medium;\"><strong>Pentru afec\u0163iuni dermatologice \u015fi reumatologice:&lt;100 \u00b5g\/L<\/strong><\/span><\/p>\n<p style=\"text-align: center;\"><span style=\"font-size: medium;\"><strong>Pentru sindrom nefrotic: 60-160 \u00b5g\/L<\/strong><\/span><\/p>\n<\/td>\n<\/tr>\n<tr>\n<td style=\"text-align: left; width: 132px;\" valign=\"top\"><span style=\"font-size: medium;\">Tacrolimus<\/span><\/td>\n<td style=\"width: 75px;\" valign=\"top\">\n<p style=\"text-align: center;\"><span style=\"font-size: medium;\">4-35 ore (adult);<\/span><\/p>\n<p style=\"text-align: center;\"><span style=\"font-size: medium;\">4-12 ore (copil)<\/span><\/p>\n<\/td>\n<td style=\"width: 90px;\" valign=\"top\">\n<p style=\"text-align: center;\"><span style=\"font-size: medium;\">2-6 zile (adult); nu se aplic\u0103 la copil<\/span><\/p>\n<\/td>\n<td style=\"width: 60px;\" valign=\"top\">\n<p style=\"text-align: center;\"><span style=\"font-size: medium;\">S\u00e2nge EDTA<\/span><\/p>\n<\/td>\n<td style=\"width: 124px;\" valign=\"top\">\n<p style=\"text-align: center;\"><span style=\"font-size: medium;\">5 zile<\/span><\/p>\n<p style=\"text-align: center;\"><span style=\"font-size: medium;\">la -20\u00b0C<\/span><\/p>\n<\/td>\n<td style=\"width: 113px;\" valign=\"top\">\n<p style=\"text-align: center;\"><span style=\"font-size: medium;\">LC-MS\/MS<\/span><\/p>\n<\/td>\n<td style=\"width: 128px;\" valign=\"top\">\n<div style=\"text-align: center;\"><span style=\"font-size: medium;\">\u2013 \u00een primele 2 luni de la transplant:<\/span><\/div>\n<div style=\"text-align: center;\"><span style=\"font-size: medium;\">15-20 \u00b5g\/L<\/span><\/div>\n<div style=\"text-align: center;\"><span style=\"font-size: medium;\">\u2013 dup\u0103<\/span><\/div>\n<div style=\"text-align: center;\"><span style=\"font-size: medium;\">\u00a02 luni de la transplant:<\/span><\/div>\n<div style=\"text-align: center;\"><span style=\"font-size: medium;\">8-15 \u00b5g\/L<\/span><\/div>\n<\/td>\n<\/tr>\n<tr>\n<td style=\"text-align: left; width: 132px;\" valign=\"top\"><span style=\"font-size: medium;\">\u0421\u0438\u0440\u043e\u043b\u0438\u043c\u0443\u0441 \u0432 \u043a\u0440\u043e\u0432\u0438<\/span><\/td>\n<td style=\"width: 75px;\" valign=\"top\">\n<p style=\"text-align: center;\"><span style=\"font-size: medium;\">46-78 ore<\/span><\/p>\n<\/td>\n<td style=\"width: 90px;\" valign=\"top\">\n<p style=\"text-align: center;\"><span style=\"font-size: medium;\">5-7 zile<\/span><\/p>\n<\/td>\n<td style=\"width: 60px;\" valign=\"top\">\n<p style=\"text-align: center;\"><span style=\"font-size: medium;\">S\u00e2nge EDTA<\/span><\/p>\n<\/td>\n<td style=\"width: 124px;\" valign=\"top\">\n<p style=\"text-align: center;\"><span style=\"font-size: medium;\">5 zile<\/span><\/p>\n<p style=\"text-align: center;\"><span style=\"font-size: medium;\">la -20\u00b0C<\/span><\/p>\n<\/td>\n<td style=\"width: 113px;\" valign=\"top\">\n<p style=\"text-align: center;\"><span style=\"font-size: medium;\">LC-MS\/MS<\/span><\/p>\n<\/td>\n<td style=\"width: 128px;\" valign=\"top\">\n<p style=\"text-align: center;\"><span style=\"font-size: medium;\">4-20 \u00b5g\/L<\/span><\/p>\n<\/td>\n<\/tr>\n<tr>\n<td style=\"text-align: left; width: 132px;\" valign=\"top\"><span style=\"font-size: medium;\">Acid micofenolic<\/span><\/td>\n<td style=\"width: 75px;\" valign=\"top\">\n<p style=\"text-align: center;\"><span style=\"font-size: medium;\">8-18 ore (adult); variabil la copil<\/span><\/p>\n<\/td>\n<td style=\"width: 90px;\" valign=\"top\">\n<p style=\"text-align: center;\"><span style=\"font-size: medium;\">Nu se aplic\u0103<\/span><\/p>\n<\/td>\n<td style=\"width: 60px;\" valign=\"top\">\n<p style=\"text-align: center;\"><span style=\"font-size: medium;\">\u0421\u044b\u0432\u043e\u0440\u043e\u0442\u043a\u0430<\/span><\/p>\n<\/td>\n<td style=\"width: 124px;\" valign=\"top\">\n<p style=\"text-align: center;\"><span style=\"font-size: medium;\">7 zile<\/span><\/p>\n<p style=\"text-align: center;\"><span style=\"font-size: medium;\">la 2-8\u00b0C<\/span><\/p>\n<\/td>\n<td style=\"width: 113px;\" valign=\"top\">\n<p style=\"text-align: center;\"><span style=\"font-size: medium;\">HPLC<\/span><\/p>\n<\/td>\n<td style=\"width: 128px;\" valign=\"top\">\n<p style=\"text-align: center;\"><span style=\"font-size: medium;\">1-3.5 \u00b5g\/mL<\/span><\/p>\n<\/td>\n<\/tr>\n<tr>\n<td style=\"text-align: left; width: 132px;\" valign=\"top\"><span style=\"font-size: medium;\">Methotrexat<\/span><\/td>\n<td style=\"width: 75px;\" valign=\"top\">\n<p style=\"text-align: center;\"><span style=\"font-size: medium;\">Cinetic\u0103 bifazic\u0103<\/span><\/p>\n<\/td>\n<td style=\"width: 90px;\" valign=\"top\">\n<p style=\"text-align: center;\"><span style=\"font-size: medium;\">-<\/span><\/p>\n<\/td>\n<td style=\"width: 60px;\" valign=\"top\">\n<p style=\"text-align: center;\"><span style=\"font-size: medium;\">\u0421\u044b\u0432\u043e\u0440\u043e\u0442\u043a\u0430<\/span><\/p>\n<p><span style=\"font-size: medium;\">\u00a0<\/span><\/td>\n<td style=\"width: 124px;\" valign=\"top\">\n<p style=\"text-align: center;\"><span style=\"font-size: medium;\">7 zile<\/span><\/p>\n<p style=\"text-align: center;\"><span style=\"font-size: medium;\">la 2-8\u00b0C protejat de lumina<\/span><\/p>\n<\/td>\n<td style=\"width: 113px;\" valign=\"top\">\n<p style=\"text-align: center;\"><span style=\"font-size: medium;\">FPIA<\/span><\/p>\n<\/td>\n<td style=\"width: 128px;\" valign=\"top\">\n<p style=\"text-align: center;\"><span style=\"font-size: medium;\">Se asociaz\u0103 cu un risc crescut de toxicitate:<\/span><\/p>\n<p style=\"text-align: center;\"><span style=\"font-size: medium;\">\u2013 valorile &gt; 5-10\u00a0 \u00b5mol\/L la 24 h de la admistrare;<\/span><\/p>\n<p style=\"text-align: center;\"><span style=\"font-size: medium;\">\u2013 valorile &gt; 0.5-1\u00a0 \u00b5mol\/L la 48 h de la administrare;<\/span><\/p>\n<p style=\"text-align: center;\"><span style=\"font-size: medium;\">\u2013 valorile &gt; 0.2\u00a0 \u00b5mol\/L la 72 h de la administrare.<\/span><\/p>\n<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\">ECLIA = metoda imunochimic\u0103 cu detec\u0163ie prin chemiluminiscen\u0163\u0103<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\">HPLC = cromatografie de lichide sub inalt\u0103 presiune<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\">LC-MS\/MS = cromatografie de lichide cuplat\u0103 cu spectrometrie de mas\u0103<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\">FPIA = fluorescent polarization immunoassay (metoda imunochimic\u0103 cu detec\u0163ie prin fluorescen\u0163a polarizat\u0103)<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\">CEDIA = cloned enzyme donor immunoassay (metoda imunoenzimatic\u0103 care utilizeaz\u0103 tehnologia ADN-ului recombinant)<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\">ISE = ion selective electrode (metoda poten\u0163iometric\u0103)<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\"><strong><span style=\"text-decoration: underline;\">Medicamente imunosupresoare<\/span><\/strong><\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\">In timp ce integritatea r\u0103spunsului imun umoral \u015fi celular este esen\u0163ial\u0103 pentru prevenirea infec\u0163iilor, in 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<p style=\"text-align: justify;\"><span style=\"font-size: medium;\">In statusul post-transplant este implicat\u0103 imunitatea de tip celular. Atat in 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 intr-o \u201ccascada\u201d de transduc\u0163ie a semnalului care va conduce in final la endocitoza antigenului in macrofage \u015fi distrugerea acestuia in lizozomi. In aceast\u0103 cascad\u0103 sunt mobiliza\u0163i ionii de calciu care determin\u0103 activarea calcineurinei, o fosfataza ce formeaz\u0103 un complex cu calmodulinul. Calcineurina activat\u0103 defosforileaz\u0103 factorul nuclear citosolic al celulelor T activate (NF-AT)<sup>\u0412<\/sup> \u015fi astfel il activeaz\u0103; acesta migreaz\u0103 c\u0103tre nucleu \u015fi se leag\u0103 de omologul s\u0103u (NF-AT)<sup>\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 il activeaz\u0103 prin legarea unei proteine, denumit\u0103 \u201c\u0163inta 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 in final la distrugerea antigenului.<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\">Au fost dezvoltate medicamente specifice care blocheaz\u0103 una sau mai multe din etapele men\u0163ionate mai sus, inhib\u00e2nd astfel distrugerea antigenului.<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\">Ciclosporina \u015fi tacrolimusul sunt polipeptide ciclice care se leag\u0103 de proteinele intracelulare denumite imunofiline (ciclosporina se leag\u0103 de ciclofilina, in timp ce tacrolimusul se leag\u0103 de imunofilina denumit\u0103 FKBP12), rezultand complexe ce blocheaz\u0103 ulterior activarea NF-AT indus\u0103 de calcineurina \u015fi in consecin\u0163\u0103 sinteza de IL-2.<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\">Un alt agent imunosupresor \u2013 rapamicina (sirolimus) \u2013 nu exercit\u0103 nici un efect asupra celulelor T, in schimb se leag\u0103 de proteina TOR cu rol critic in activarea celulei T.<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\">Micofenolatul mofetil (MMT) este un antibiotic ce este hidrolizat in celule in acid micofenolic liber. Acest agent este un inhibitor potent al inozin-monofosfat dehidrogenazei \u015fi al guanozin-monofosfat sintetazei, impiedicand in final sinteza ADN-ului.<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\">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 adverse<sup>2<\/sup>.<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\"><strong>Ciclosporina A <\/strong>este recomandat\u0103 pentru a preveni rejetul de gref\u0103 in transplantul alogenic de rinichi, ficat, inim\u0103 \u015fi pl\u0103mani-inim\u0103; de asemenea mai este utilizat ca medicament de prim\u0103 sau a doua linie in tratamentul bolii acute grefa contra-gazda survenit\u0103 dup\u0103 transplantul de m\u0103duv\u0103 osoas\u0103, in artrita reumatoid\u0103 sever\u0103, cat \u015fi in unele forme grave de psoriazis.<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\">Nivelul sangvin maxim este atins dup\u0103 aproximativ 3.5 ore de la administrare; cca 20-40% din doza administrat\u0103 este absorbit\u0103 intestinal \u015fi este metabolizat\u0103 la primul pasaj hepatic. Izoenzima CYP3A4 a citocromului P450 este responsbil\u0103 de metabolizarea ciclosporinei in cel pu\u0163in 30 metaboli\u0163i. Deoarece un num\u0103r mare de medicamente pot induce activitatea enzimei sau pot fi metabolizate de CYP3A4 (antibiotice, antifungice sau alte imunosupresoare) asocierea acestora poate altera nivelurile ciclosporinei in s\u00e2nge \u015fi complica astfel tratamentul.<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\">Ciclosporina are un interval terapeutic ingust, cu reac\u0163ii adverse frecvente, ceea ce face ca monitorizarea concentra\u0163iei sale in s\u00e2nge s\u0103 fie esen\u0163ial\u0103.<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\">Deoarece 80% din ciclosporin\u0103 este sechestrat\u0103 in eritrocite se recomand\u0103 ca nivelurile medicamentului s\u0103 fie determinate in probe de sange integral. In primele 2 luni posttransplant dozele sunt ajustate astfel incat s\u0103 se men\u0163in\u0103 concentra\u0163iile intre 150 \u03bcg\/L \u015fi 400 \u03bcg\/L. Concentra\u0163iile ob\u0163inute in <em>trough samples<\/em> pot varia ins\u0103 in func\u0163ie de protocolul clinic, tipul alogrefei, riscul de rejet, administrarea concomitent\u0103 a unor alte imunosupresoare \u015fi toxicitate. Dup\u0103 primele 2 luni \u0163inta terapeutic\u0103 este in general mai redus\u0103 (intre 75 \u015fi 300 \u03bcg\/L).<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\">Reac\u0163iile adverse ale ciclosporinei pot s\u0103 apar\u0103 in orice organ; valorile concentra\u0163iei maxime (<em>trough samples<\/em>) &gt;500 \u03bcg\/L sunt asociate cu nefrotoxicitate, cea mai frecvent\u0103 reac\u0163ie advers\u0103, inso\u0163it\u0103 de hiperkaliemie, hiperuricemie, hipertensiune arteriala \u015fi hiperplazie gingivala.<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\">Alte reac\u0163ii adverse includ efecte neurologice (tremor, convulsii, cefalee, parestezii, confuzie), dermatologice (hirsutism, rash), hepatotoxicitate, tulburari gastrointestinale (diaree, grea\u0163\u0103, v\u0103rs\u0103turi, anorexie, discomfort abdominal), hematologice (leucopenie, anemie, trombocitopenie), complica\u0163ii infec\u0163ioase, reac\u0163ii de hipersensibilitate. In plus, exist\u0103 un risc crescut de limfoame, in special ale SNC<sup>2;3<\/sup>.<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: small;\">\u00a0<\/span><\/p>\n<p style=\"text-align: justify;\"><strong><span style=\"font-size: small;\">\u0411\u0438\u0431\u043b\u0438\u043e\u0433\u0440\u0430\u0444\u0438\u044f<\/span><\/strong><\/p>\n<div style=\"text-align: justify;\"><span style=\"font-size: small;\">1. Laborator Synevo. Referin\u0163e specifice tehnologiei de lucru utilizate. 2010. Ref Type: Catalog.<\/span><\/div>\n<div style=\"text-align: justify;\"><span style=\"font-size: small;\">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<div style=\"text-align: justify;\"><span style=\"font-size: small;\">3. Mayo Clinic\/Mayo Medical Laboratories Test Catalogs and Guides. Cyclosporine, Blood. www.mayomedicallaboratories.com. Ref Type: Internet Communication.<\/span><\/div>\n<div style=\"text-align: justify;\"><span style=\"font-size: small;\">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":"<p>\u0426\u0438\u043a\u043b\u043e\u0441\u043f\u043e\u0440\u0438\u043d \u2013 11-\u0430\u043c\u0438\u043d\u043e\u043a\u0438\u0441\u043b\u043e\u0442\u043d\u044b\u0439 \u0446\u0438\u043a\u043b\u0438\u0447\u0435\u0441\u043a\u0438\u0439 \u043f\u0435\u043f\u0442\u0438\u0434, \u043e\u0431\u043b\u0430\u0434\u0430\u044e\u0449\u0438\u0439 \u043c\u043e\u0449\u043d\u044b\u043c \u0438\u043c\u043c\u0443\u043d\u043e\u0441\u0443\u043f\u0440\u0435\u0441\u0441\u0438\u0432\u043d\u044b\u043c \u0434\u0435\u0439\u0441\u0442\u0432\u0438\u0435\u043c, \u0441\u0432\u044f\u0437\u0430\u043d\u043d\u044b\u043c \u0441 \u043f\u043e\u0434\u0430\u0432\u043b\u0435\u043d\u0438\u0435\u043c \u0430\u043a\u0442\u0438\u0432\u043d\u043e\u0441\u0442\u0438 \u0422-\u043b\u0438\u043c\u0444\u043e\u0446\u0438\u0442\u043e\u0432. \u042d\u0442\u043e \u043e\u0434\u0438\u043d \u0438\u0437 \u043e\u0441\u043d\u043e\u0432\u043d\u044b\u0445 \u043f\u0440\u0435\u043f\u0430\u0440\u0430\u0442\u043e\u0432, \u043f\u0440\u0438\u043c\u0435\u043d\u044f\u0435\u043c\u044b\u0445 \u0432 \u0438\u043c\u043c\u0443\u043d\u043e\u0441\u0443\u043f\u0440\u0435\u0441\u0441\u0438\u0432\u043d\u043e\u0439 \u0442\u0435\u0440\u0430\u043f\u0438\u0438 \u043f\u0440\u0438 \u0442\u0440\u0430\u043d\u0441\u043f\u043b\u0430\u043d\u0442\u0430\u0446\u0438\u0438 \u043e\u0440\u0433\u0430\u043d\u043e\u0432, \u0441\u0443\u0449\u0435\u0441\u0442\u0432\u0435\u043d\u043d\u043e \u043f\u043e\u0432\u044b\u0448\u0430\u044e\u0449\u0438\u0439 \u0432\u0435\u0440\u043e\u044f\u0442\u043d\u043e\u0441\u0442\u044c \u0443\u0441\u043f\u0435\u0448\u043d\u043e\u0433\u043e \u0438\u0441\u0445\u043e\u0434\u0430 \u044d\u0442\u0438\u0445 \u043e\u043f\u0435\u0440\u0430\u0446\u0438\u0439.<\/p>\n<p>\u0426\u0438\u043a\u043b\u043e\u0441\u043f\u043e\u0440\u0438\u043d \u0432\u0432\u043e\u0434\u044f\u0442 \u0432\u043d\u0443\u0442\u0440\u0438\u0432\u0435\u043d\u043d\u043e \u0438\u043b\u0438 \u043f\u0435\u0440\u043e\u0440\u0430\u043b\u044c\u043d\u043e, \u043f\u0440\u0438 \u044d\u0442\u043e\u043c \u0430\u0431\u0441\u043e\u0440\u0431\u0446\u0438\u044f \u0438\u0437 \u0436\u0435\u043b\u0443\u0434\u043e\u0447\u043d\u043e-\u043a\u0438\u0448\u0435\u0447\u043d\u043e\u0433\u043e \u0442\u0440\u0430\u043a\u0442\u0430 \u0432\u0430\u0440\u0438\u0430\u0431\u0435\u043b\u044c\u043d\u0430, \u043f\u043b\u043e\u0445\u043e \u043f\u0440\u0435\u0434\u0441\u043a\u0430\u0437\u0443\u0435\u043c\u0430 \u0438 \u043c\u043e\u0436\u0435\u0442 \u0431\u044b\u0442\u044c \u043d\u0435\u043f\u043e\u043b\u043d\u043e\u0439. \u0412\u0441\u0430\u0441\u044b\u0432\u0430\u043d\u0438\u0435 \u0446\u0438\u043a\u043b\u043e\u0441\u043f\u043e\u0440\u0438\u043d\u0430 \u043f\u0440\u0438 \u043f\u0435\u0440\u043e\u0440\u0430\u043b\u044c\u043d\u043e\u043c \u043f\u0440\u0438\u0435\u043c\u0435 \u043c\u043e\u0436\u0435\u0442 \u0438\u0437\u043c\u0435\u043d\u044f\u0442\u044c\u0441\u044f \u0432 \u0437\u0430\u0432\u0438\u0441\u0438\u043c\u043e\u0441\u0442\u0438 \u043e\u0442 \u0432\u0440\u0435\u043c\u0435\u043d\u0438, \u043f\u0440\u043e\u0448\u0435\u0434\u0448\u0435\u0433\u043e \u043f\u043e\u0441\u043b\u0435 \u043e\u043f\u0435\u0440\u0430\u0446\u0438\u0438, \u0432\u0432\u0435\u0434\u0435\u043d\u043d\u043e\u0439 \u0434\u043e\u0437\u044b, \u0436\u0435\u043b\u0443\u0434\u043e\u0447\u043d\u043e-\u043a\u0438\u0448\u0435\u0447\u043d\u044b\u0445 \u0434\u0438\u0441\u0444\u0443\u043d\u043a\u0446\u0438\u0439, \u0438\u0437\u043c\u0435\u043d\u0435\u043d\u0438\u044f \u043e\u0442\u0442\u043e\u043a\u0430 \u0436\u0435\u043b\u0447\u0438, \u0431\u043e\u043b\u0435\u0437\u043d\u0435\u0439 \u043f\u0435\u0447\u0435\u043d\u0438 \u0438 \u043f\u0440\u0438\u0435\u043c\u0430 \u043f\u0438\u0449\u0438. \u0426\u0438\u043a\u043b\u043e\u0441\u043f\u043e\u0440\u0438\u043d \u0440\u0430\u0441\u043f\u0440\u0435\u0434\u0435\u043b\u044f\u0435\u0442\u0441\u044f, \u0433\u043b\u0430\u0432\u043d\u044b\u043c \u043e\u0431\u0440\u0430\u0437\u043e\u043c, \u0432\u043d\u0435 \u043a\u0440\u043e\u0432\u044f\u043d\u043e\u0433\u043e \u0440\u0443\u0441\u043b\u0430. \u0412 \u043a\u0440\u043e\u0432\u0438 \u0430\u043a\u0442\u0438\u0432\u043d\u043e\u0435 \u0432\u0435\u0449\u0435\u0441\u0442\u0432\u043e \u043f\u0440\u0438\u0441\u0443\u0442\u0441\u0442\u0432\u0443\u0435\u0442 \u0432 \u043f\u043b\u0430\u0437\u043c\u0435 (33-47%), \u0432 \u043b\u0438\u043c\u0444\u043e\u0446\u0438\u0442\u0430\u0445 (4-9%), \u0432 \u0433\u0440\u0430\u043d\u0443\u043b\u043e\u0446\u0438\u0442\u0430\u0445 (5-12%) \u0438 \u0432 \u044d\u0440\u0438\u0442\u0440\u043e\u0446\u0438\u0442\u0430\u0445 (41-58%). \u0421\u0432\u044f\u0437\u044b\u0432\u0430\u043d\u0438\u0435 \u0441 \u0431\u0435\u043b\u043a\u0430\u043c\u0438 \u043f\u043b\u0430\u0437\u043c\u044b, \u043f\u0440\u0435\u0438\u043c\u0443\u0449\u0435\u0441\u0442\u0432\u0435\u043d\u043d\u043e \u0441 \u043b\u0438\u043f\u043e\u043f\u0440\u043e\u0442\u0435\u0438\u043d\u0430\u043c\u0438, \u0441\u043e\u0441\u0442\u0430\u0432\u043b\u044f\u0435\u0442 90%. \u041f\u0435\u0440\u0438\u043e\u0434 \u043f\u043e\u043b\u0443\u0432\u044b\u0432\u0435\u0434\u0435\u043d\u0438\u044f \u0446\u0438\u043a\u043b\u043e\u0441\u043f\u043e\u0440\u0438\u043d\u0430 \u0438\u043c\u0435\u0435\u0442 \u0437\u043d\u0430\u0447\u0438\u0442\u0435\u043b\u044c\u043d\u044b\u0435 \u0438\u043d\u0434\u0438\u0432\u0438\u0434\u0443\u0430\u043b\u044c\u043d\u044b\u0435 \u0440\u0430\u0437\u043b\u0438\u0447\u0438\u044f \u0438 \u0441\u043e\u0441\u0442\u0430\u0432\u043b\u044f\u0435\u0442 \u043e\u0442 6 \u0447\u0430\u0441\u043e\u0432 \u0443 \u0437\u0434\u043e\u0440\u043e\u0432\u044b\u0445 \u043b\u044e\u0434\u0435\u0439 \u0434\u043e 20 \u0447\u0430\u0441\u043e\u0432 \u0443 \u043f\u0430\u0446\u0438\u0435\u043d\u0442\u043e\u0432 \u0441 \u0442\u044f\u0436\u0435\u043b\u044b\u043c\u0438 \u0437\u0430\u0431\u043e\u043b\u0435\u0432\u0430\u043d\u0438\u044f\u043c\u0438 \u043f\u0435\u0447\u0435\u043d\u0438. \u0423 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