გზა MDR-TB ახალი თერაპიისკენ

marika erisTavi

“samSabaToba”, 04.05.10.

amJamad gamoyenebuli reJimebi multikomponentiani da xangrZlivad iniSneba;

Znelia aseTi grZeli da kompleqsuri reJimis Sesruleba, xSiria mkurnalobaSi Secdomebic, im pacientTa Sorisac ki, romelTac wamlisadmi mgrZnobiare tuberkulozi aqvT;

swored amitom mniSvnelovania Zlieri antibiotikis arseboba, romelic ufro swrafad daamarcxebs infeqcias.

Moxifloxacin PA-824 TMC 207 Quinolone TBK-613 Nitroimidazoles Mycobacterial Gyrase Inhibitors Riminophenazines InhA Inhibitors New Generation Diarylquinoline Bi-functional Molecules Phenotypic Screening Tryptanthrins LeuRS Inhibitors GSK Whole-Cell Screening Malate Synthase Inhibitors Energy Metabolism Inhibitors RNA Polymerase Inhibitors Natural Products Menaquinone Biosynthesis Inhibitors Protease Inhibitors Topoisomerase I Inhibitors

TMC207: uaxlesi antibaqteriuli preparatebis jgufi; diarqinoloni (Dairylquinoline):

axasiaTebs antituberkulozuri moqmedebis axali meqanizmi _ ainhibirebs mikobaqteriul ATP-sinTetazas;

in vitro ainhibirebs wamlebisadmi mgrZnobiare da wamlebisadmi rezistentul M. tuberculosis;

iCens baqteriocidul aqtivobas pacientebSi, romlebsac aqvT wamlisadmi mgrZnobiare filtvis tuberkulozi

kvlevis meTodebi:

Catarda orsafexuriani, randomizebuli, multicentruli, placeboTi kontrolirebadi cda, romelic miznad isaxavda TMC 207-is:

usafrTxoebis; farmakokinetikisa; antimikrobuli aqtivobis Sefasebas;

kvleva Catarda 47 filtvis formis, mgb(+), warsulSi II rigis TB preparatebiT aranamkurnaleb MDR-TBpacientze:

maTgan 23-s mkurnalobdnen: I etapze TMC207/400 mg; 2 kviris

ganmavlobaSi, erTxel dReSi II etapze TMC207/200 mg; 6 kviris

ganmavlobaSi, 3-jer dReSi;

24 pacients umkurnales placeboTi;

sakvlevi populacia ZiriTadad Sedgeboda mamri (74%), Savkaniani (55%), aiv

negatiuri (87%) individebisagan, saSualo asakiT 33 weli (18dan 65

wlamde)

pacientebi gaanawiles kvlevis centrebis;

filtvis kavitaciis mixedviT

≥2 sm bilateralurad, ≥2 sm unilateralurad, <2 sm.

mocemuli dozebi winaswar Catarebuli kvlevis safuZvelze SeirCa

dRiuri 400 mg-iani doza saWiroa maqsimaluri baqteriociduli aqtivobisaTvis;

kviraSi 3jer 200 mg-iani dozireba ki plazmuri koncentraciis SesanarCuneblad;

preparatebis mimarT mgrZnobeloba ganisazRvra molekuluri genotipirebis meTodebiT, xolo kulturis konvertaciis Sefaseba xdeboda Txevad niadagze MGIT sistemiT;

orive SemTxvevaSi TMC207-Tan erTad samkurnalo reJimSi gamoiyeneboda II rigis 5 standartuli TB preparati:

Km, Ofx, Eth, Z, Cs (an terizidoni);

TMC207-Tan kombinaciaSi 8 kviriani kursis Semdeg standartuli mkurnaloba 96 kvira gagrZelda;

kvlevaSi ar moxda Semdegi kategoriis pacientebis CarTva:

eqstrapulmonaluri TB pacientebi; pacientebi visi testic dadebiTi iyo aiv-ze, CD4+

iyo 300-ze naklebi da miRebuli hqondaT antiretrovirusuli da/an antimikozuri medikamentebi ukanaskneli 90 dRis ganmavlobaSi;

pacientebi mniSvnelovani kardialuri ariTmiiT;

aseve gamoiricxnen pacientebi Semdegi maxasiaTeblebiT:

hipermgrZnobeloba wamlebisadmi, alkoholis an narkotikis moxmareba, Tanmxlebi daavadebebi, atipiuri laboratoriuli Sedegebi, fexmZimoba, an ZuZuTi kveba, monawileoba sxva klinikur kvlevebSi.

monacemebi statistikurad SAS Software-is programis daxmarebiT damuSavda

47 CarTuli pacientidan kvlevaSi sabolood monawileoba 41-ma miiRo (20-ma TMC207-is jgufidan da 21-ma placebos jgufidan);

atipiuri, an mwvave gverdiTi movlenebi ar gamovlenila, IV xarisxis diabeturi ketoacidozi ganviTarda 1 SemTxvevaSi TMC207 jgufidan da IV xarisxis pnevmoToraqsi 1 SemTxvevaSi placebos jgufidan;

Sedegebi:

TMC207-is jgufis pacientebSi placebos jgufis pacientebisgan gansxvavebiT gamovlinda mniSvnelovnad gaxSirebuli gulisreva (26% vs. 4%, P = 0.04);

plazmur koncentraciaSi ar iqna SeniSnuli araviTari mniSvnelovani gansxvaveba TMC207-is pacientebis im jgufebs Soris, romelTac ganicades an ar ganicades kulturebis konversia;

standartul Terapiaze TMC207-is damatebam

Seamcira kulturis konversiis dro placebos jgufTan SedarebiT;

gazarda konversirebuli naxvelis kulturis mqone pacientebis ricxvi (48% vs 9%).

TMC207 jgufSi mkveTrad daeca koloniis warmomqmneli erTeulebis ricxvi placebos jgufTan SedarebiT;

TMC207-is klinikuri aqtivoba adasturebs,

rom ATP-sinTetaza kargi samiznea tuberkulozis

samkurnalod

tuberkulozis Tagvis modelSi TMC207 aris aqtiuri izoniazidTan, rifampinTan da pirazinamidTan kombinaciaSi, amasTan TMC207-is damatebam am sami wamlis kombinaciasTan daaCqara bacilebis ganadgureba da gvaCvena rom is sinergistulad urTierTqmedebs pirazinamidTan;

wamlebisadmi sensitiuri tuberkulozian Tagvis modelSi TMC207 aZlierebs meore rigis wamlebis kombinaciis antibaqteriul aqtivobas

gmadlobT

yuradRebisaTvis