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axali TB preparatebi , axali samkurnalo reJimebi : gza TB mkurnalobis gaumjobesebisaken

axali TB preparatebi , axali samkurnalo reJimebi : gza TB mkurnalobis gaumjobesebisaken. neli solomonia ; samecniero seminari ; 24.11.09. axali TB samkurnalo reJimebi : ra sWirdebaT qveynebs ? agvisto ; 2009 sensitiuri tuberkulozis ukve arsebuli da axali samkurnalo reJimebis Sefaseba.

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axali TB preparatebi , axali samkurnalo reJimebi : gza TB mkurnalobis gaumjobesebisaken

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  1. axaliTBpreparatebi, axalisamkurnaloreJimebi: gzaTBmkurnalobisgaumjobesebisaken nelisolomonia; samecnieroseminari; 24.11.09

  2. axaliTBsamkurnaloreJimebi:rasWirdebaTqveynebs?agvisto; 2009 sensitiurituberkulozisukvearsebulidaaxalisamkurnaloreJimebisSefaseba

  3. TB maRali tvirTis mqone 5 qveynis magaliTze Sefasda sensitiuri TB-is mkurnalobis ukve arsebuli da axali reJimebi: • brazilia; • CineTi; • indoeTi; • kenia; • samxreT afrika

  4. ukve arsebuli samkurnalo reJimebis Sefasebisas aqcenti keTdeboda: • mkurnalobis xangrZlivobaze; • periodulobaze (yoveldRe, Tu kviraSi 3-jer); • oraluri preparatebis upiratesobaze; • fiqsirebuldoziani preparatebis gamoyenebaze; • gverdiTi movlenebis ganviTarebis sixSireze; • HIV/AIDS-TB koinfeqciis marTvis Taviseburebebze;

  5. mTavari mimarTuleba – samkurnalo reJimis xangrZlivobis Semcireba • sensitiuri tuberkulozis mkurnalobaSi izoniazidismoqsifloqsaciniT Canacvleba; • mkurnalobis xangrZlivobis 6-dan 4 Tvemde Semcireba.

  6. Historic Opportunity to Develop New Therapeutic Options for TB 1950 1970 1980 2010 1960 1974 BMRC Trials add RIF & PZA 1963 Rifampin (RIF) discovered 1970 BMRC Trials add RIF • 1952 • 1st regimen: • Streptomycin • PAS • Isoniazid 2005 Trials substitute Moxifloxacin into regimen 1954 Pyrazainimide (PZA) discovered – but liver toxicity Standard Therapy 2 months: rifampin, isoniazid, pyrazinamide, ethambutol + 4 months: rifampin, isoniazid Standard Regimen by 1960s based on 1952 drugs Rx target: 3-4 months Rx shortened to 6 months Rx shortened to 9 months Rx lasts from 12-24 months

  7. In an animal study*, moxifloxacin regimen shortened treatment duration by 2 months 10 Legend 9 Untreated 8 7 2 months rifampin, isoniazid and pyrazinimide followed by 4 months rifampin and isoniazid 6 5 Log CFU in entire lung 4 2 months rifampin, moxifloxacin and pyrazinimide followed by 4 months rifampin and moxifloxacin 3 2 1 0 0 1 2 3 4 5 6 Duration of treatment (months) *In vivo data does not predict clinical response.

  8. dadebiTiSedegebi: • mkurnalobisxangrZlivobisSemcirebazrdismkurnalobisadmidamyolobas; • amcirebswyvetilimkurnalobisSemTxvevebs; • axdensrezistentobisganviTarebisprevencias (qinolonebi???); • Moxi-is gamoyenebaSeiZlebaARV mkurnalobispirobebSi, vinaidanR-sgangansxvavebiTmciredaxdenscitoqrom P-450 fermentisinducirebas; • izoniazidisMoxi-iTCanacvlebaTBmaRalitvirTismqoneqveynebSicSesaZlebelsgaxdisLTBI-s H-iTmkurnalobas.

  9. uaryofiTi Tu dadebiTi Sedegebi??? • samkurnalo reJimSi moqsifloqsacinis CarTva, xangrZlivobis Semcirebis miuxedavad, gamoiwvevs mkurnalobis xarjebis gazrdas; nacionaluri programebis umetesobas danaxarjis gazrda gamarTlebulad miaCnia.

  10. uaryofiTi Sedegebi: • sensitiuri TB-is samkurnalo reJimSi moqsifloqsacinis gamoyenebam SesaZloa problemebi Seqmnas mis mimarT pirveladi rezistentobis SemTxvevaSi; Sesaswavlia gazrdis Tu ara Moxi-is gamoyeneba qinolonebis mimarT meoradi rezistentobis ganviTarebis albaTobas; • Moxi-is gamoyenebas Tan axlavs toqsiuri gverdiTi movlenebi; • Moxi-is gamoyeneba ar SeiZleba bavSvebSi.

  11. gansxvavebuli monacemebis dafiqsireba mianiSnebs TiToeul qveyanaSi axali reJimebis adaptirebis procesSi monacemebis dagrovebis da informaciis urTierTgacvlis aucileblobaze; • axali samkurnalo reJimebis adaptirebis procesSi Sesabamisoba unda iyos janmo-s rekomendaciebsa da nacionaluri programis farglebSi ganxorcielebul cvlilebes Soris.

  12. 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

  13. moqsifloqsacini; qinolonebis jgufi; 8-methoxy fluoroquinolone: • axdens M. tuberculosis mier gamomuSavebuli ferment dnm-hirazas inhibirebas; • mcired monawilebs citoqrom P450-is metabolizmSi da ARV Terapiis aucileblobis SemTxvevaSi upiratesoba aqvs I rigis sxva preparatebTan SedarebiT; • 2002-2003 w-dan dawyebuli preklinikuri kvlevebi adastureben izoniazidis CancvlebiT sensitiuri tuberkulozis mkurnalobis xangrZlivobis Semcirebis SesaZleblobas.

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

  15. gmadlobT yuradRebisaTvis

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