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rezistentuli tuberkulozis mkurnaloba Sors aris srulyofilebisagan

Aaxali antituberkulozuri preparati _ PA 824 ganviTareba da kvlevebi lika trapaiZe, “samSabaToba”, 26.01.10. rezistentuli tuberkulozis mkurnaloba Sors aris srulyofilebisagan

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rezistentuli tuberkulozis mkurnaloba Sors aris srulyofilebisagan

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  1. Aaxali antituberkulozuri preparati _ PA 824 ganviTareba da kvlevebilika trapaiZe, “samSabaToba”, 26.01.10

  2. rezistentuli tuberkulozis mkurnaloba Sors aris srulyofilebisagan msoflios wamyvan farmakologiur kompaniebSi axali preparatebis Sesaqmnelad mimdinare muSaobis ZiriTadi mimarTulebebia: • axali, efeqturi TB preparatis Seqmna; • rezistentuli tuberkulozis mkurnalobis vadebis Semcireba; preparatebis umravlesoba jerjerobiT kvlevis fazaSia.

  3. PA-824: uaxlesi antibaqteriuli preparatebis jgufi; nitroimidazoli: • aqvs baqteriociduli da masterizebeli moqmedeba; • efeqturia rogorc sensitiuri, ise rezistentuli TB-s samkurnalod; • SeiZleba ARV TerapiasTan kombinaciaSi gamoyeneba; • 2005 wlidan CarTulia klinikuri kvlevebis I stadiaSi.

  4. nitroimidazolebisantituberkulozuri aqtioba pirvelad aRwerili iqna 1993 wels, Tumca Semdgomi ganviTareba ver hpova, radgan naerTebi mutagenuri aRmoCnda. SemdgomSi gafarToebuli kvlevebis Sedegad miRebul iqna PA-824

  5. ar arsebobs mtkicebuleba genotoqsiuri kompleqsebiT standartul gamokvlevebSi PA-824-s mutaciis Sesaxeb; • ar SeiniSneba mniSvnelovani urTierTqmedeba citoqromul P450-Tan; • ar SeiniSneba aqtivoba gram-dadebiTi da gram-uaryofiTi baqteriebis farTo speqtris winaaRmdeg.

  6. PA-824-ze kvlevebi mimdinareobs 2002 wlidan • TB alliance-isfarglebSi; • kaliforniis bioteqnologiur kompaniaSi (Chiron Corporation); • aSS alergiisa da infeqciur daavadebaTa erovnuli centris da • Research TriangleInstitute monawileobiT. P

  7. sawyisi monacemebis mixedviT, PA-824 efeqturia rogorc sensitiuri, ise rezistentuli Stamebis winaaRmdeg in vitro (yvela izolatSi); P • preklinikurma gamocdam aCvena, rom cxovelebSi preparati efeqturia rogorc arsebul preparatebTan SedarebiT, aseve maTTan kombinaciaSi; • gansazRvrul iqna naerTis usafrTxoebisa da farmakokinetikis modeli misi klinikur gamocdaSi CarTvis SesaZleblobis Sefasebis mizniT.

  8. TagvebSi 9 dRis ganmavlobaSi Per.os miRebis Semdeg PA-824 efeqturi iyo 50, 100 da 300 mg/kg wonaze. naerTis suspenzia momzadda ciklodeqstrin- lecitinze. misi aqtioba Sedarda H, R, Mfx-Tan. PA-824 100 mg/kg doziT iseTive aqtiuri iyo, rogorc Mfx 100 mg/kg da H 25 mg/kg, da bevrad ufro aqtiuri, vidre R 20 mg/kg.

  9. xangrZlivad (6 Tvis ganmavlobaSi) miRebisas, eqsperimentebSi, sadac PA-824 gamoiyenes Hnacvlad ( 2RPA-824Z+ 4RPA-824, an 6RPA-824), 19 Tagvidan relafsi ganviTarda 2-Si, maSin roca standartuli reJimis (2RHZ+4RH) dros 46 Tagvidan arcerTSi ar ganviTarda relafsi. • raime mniSvnelovani gansxvaveba PA-824- sa da sxva preparatebiT monoTerapias Soris (H- 25 mg/kg, R- 10 mg/kg, Gfx- 100 mg/kg da Mfx- 100 mg/kg) nanaxi ar iqna.

  10. PA-824-ma aCvena mZlavri viwro speqtris aqtioba mgb-s winaaRmdeg; • ar axasiaTebs jvaredini rezistentoba sxva tubsawinaaRmdego preparatebTan; • TagvebSi minimaluri efeqturi doza iyo 12, 5 mg/kg dReSi, minimaluri baqtericiduli doza monoTerapiis dros- 100 mg/kg; • intensiur fazaSi iseTive efeqturi iyo TagvebSi, rogorc H adamianebSi, H-Tan kombinaciaSi PA-824-ma moaxdina izoniazid-rezistentuli mutaciis prevencia; • PA-824-ma aCvena aqtioba iseT SemTxvevebSi, roca 2- Tviani intensiuri fazis (H, R, Z) Semdeg rCeboda bacilagamoyofa.

  11. preklinikuri kvlevebis dasrulebis Semdeg 2005 wels preparati gadavida klinikuri kvlevebis I stadiaSi, sadac janmrTel voluntarebSi erTjeradi da jeradi doziT micemisas Sefasebul iqna PA-824-is • usafrTxoeba; • tolerabiluroba; • farmakokinetika; • ADME (absorbcia, distribucia, metabolizmi da eqskrecia).

  12. dReisaTvis Sesrulebulia I stadiis 6 faza, rac gulisxmobs: • randomizebul erTjeradi mzardi doziT kvlevas janmrTel mamakac voluntarebSi; • randomizebul mravaljeradi mzardi doziT kvlevas orive sqesis voluntarebSi; • erTjeradi doziT gamokvlevas normaluri kvebisa da SimSilis pirobebSi; • PA-824-is radiomoniSnuli 2 erTjeradi doziT kvlevas orive sqesis voluntarebSi misi ADME Sefasebis mizniT.

  13. niu-iorkSi Catarda kvleva janmrTel kontigentSi kvlevisaTvis SerCeul iqna: • orive sqesis 77 piri; • aqedan 58 maTgani iRebda PA-824-s; • 19- placebos. es 77 piri warmoadgenda sxvadasxva rasobriv jgufs

  14. erTjeradi dozis SemTxvevaSi PA 824-is koncentracia meryeobda: • 0,3+ 0,1 g/ml-dan (50 mg dozis jgufi); • 2,9+0,5 g/ml-mde (1500 mg dozis jgufi). sruli gamoyofa meryeobda: • 7,5+3,9 g.sT/ml-dan (50 mg dozis jgufi); • 101,8+25,3 g.sT/ml-mde (1500 mg dozis jgufi).

  15. gverdiTi movlenebi (guliscemis aCqareba, gulisreva, GRebineba da a.S.) SeiniSna mxolod placebos jgufSi; • dadasturda, rom PA-824 kargad aitaneba • rogorc erTjerad 100 mg-mde doziT 5 dRis ganmavlobaSi; • aseve erTjerad 600 mg-mde doziT 7 dRis ganmavlobaSi ( Global Alliance for TB Drug Development, 40 Wall Street, New York, New York 10005,1 and RTI International, 3040 Cornwallis Road, P.O. Box 12194, Research Triangle Park, North Carolina 277092).

  16. mravaljeradi dozirebis stadia (CL 102) Sewyvetil iqna kreatininis momatebis gamo, romelic Seqcevadi aRmoCnda; • PA- 824-s Sewova orive stadiaSi zomierad swrafad moxda; • maqsimaluri koncentracia miRweul iqna 4 da 5 saaTSi;

  17. Catarda gamokvleva PA-824 miRebis fonze kreatininis zomieri momatebis mizezis dasadgenad • gamokvleul iqna orive sqesis 45 janmrTeli piri; • maT miecaT 800 an 1000 mg PA- 824 8 dRis ganmavlobaSi.

  18. dadasturda, rom kreatininis Seqcevadi momateba ar iyo dakavSirebuli Tirkmlis funqciis darRvevasTan (Antimicrobial Agents and Chemotherapy. September 2009. p. 3726-3733 Ann M. Ginsberg, Martino W. Laurenzi, Doris J. Rouse, Karl D. Whitney, and Melvin K. Spigelman). • aRmoCnda, rom PA-824-is moqmedebiT xdeba cilis katabolizmis gazrda, gorglovani filtraciis daqveiTeba da kreatininis sekreciis Semcireba Tirkmlis proqsimalur milakebSi, Cveulebriv, konkurentuli inhibirebis gziT. • kreatininis momateba aRmoCnda droebiTi, Seqcevadi da klinikurad umniSvnelo, rogorc, magaliTad, cimetidinis, trimetoprimis, an pirimetaminis miRebis fonze ganviTarebuli hiperkreatininemia.

  19. kvlevebma aCvena, rom PA-824 kargad asatani preparatia raime gansakuTrebuli, dozaze damokidebuli gverdiTi reaqciebis gareSe; • 2007 wels PA-824 mieniWa samedicino produqtis statusi evropis samedicino saagentos (EMEA) da amerikis sakvebisa da wamlebis administraciis (FDA) mier.

  20. 2007 wlis bolos daiwyo pirveli klinikuri gamocda bacilagamomyof pacientebSi (kvleva Catarda keiptaunSi, samxreT afrikaSi) pacientebi dayofilni iyvnen 2 jgufad; • PA-824 eZleodaT monoTerapiis saxiT, sxvadasxva dozebiT; • 14 dRis ganmavlobaSi; PA-824 efeqturi iyo kvlevaSi gamoyenebuli mcire doziTac ki

  21. 05.2008 - 07.2009 periodSi PA-824 klinikuri ganviTareba SeCerda, radgan cxovelebSi nanaxi iqna toqsiurobis monacemebi; • Catarda damatebiTi kvlevebi, ris Semdegac ganaxlda preparatis klinikuri ganviTarebis programa; • dagegmilia preparatis gamocdis meore etapi Semcirebuli dozebiT. gamocdis programa ukve daSvebulia, Tumca pacientebis registracia jer ar dawyebula; • momdevno ganviTareba moicavs PA-824-is testirebas sxva antituberkulozur preparatebTan kombinaciaSi, raTa Sefasdes misi potenciali tuberkulozis mkurnalobis gaumjobesebaSi.

  22. gmadlobT yuradRebisaTvis

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