Transcript New Drugs, New Regimens: The Way Forward in TB Treatment

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
TB maRali tvirTis mqone 5 qveynis magaliTze Sefasda sensitiuri
TB-is mkurnalobis ukve arsebuli da axali reJimebi:
 brazilia;
 CineTi;
 indoeTi;
 kenia;
 samxreT
afrika
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;
mTavari mimarTuleba –
samkurnalo reJimis xangrZlivobis Semcireba
 sensitiuri tuberkulozis
mkurnalobaSi izoniazidis
moqsifloqsaciniT Canacvleba;
 mkurnalobis xangrZlivobis
6-dan 4 Tvemde Semcireba.
Historic Opportunity to Develop New
Therapeutic Options for TB
1950
1960
1963
1952
Rifampin
1st regimen:
(RIF)
• Streptomycin
discovered
• PAS
1954
• Isoniazid Pyrazainimide
(PZA)
discovered –
but liver toxicity
1970
1980
1974
1970
BMRC Trials BMRC Trials add
RIF & PZA
add RIF
Standard Therapy
2 months: rifampin, isoniazid,
pyrazinamide, ethambutol
+
4 months: rifampin, isoniazid
2010
2005
Trials substitute
Moxifloxacin into
regimen
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
Log CFU in entire lung
In an animal study*, moxifloxacin regimen
shortened treatment duration by 2 months
10
9
8
7
6
5
4
3
2
1
0
Legend
Untreated
2 months rifampin,
isoniazid and pyrazinimide
followed by 4 months
rifampin and isoniazid
2 months rifampin,
moxifloxacin and
pyrazinimide followed by 4
months rifampin and
moxifloxacin
0
1
2
3
4
5
6
Duration of treatment (months)
*In vivo data does not predict clinical response.
dadebiTi Sedegebi:
 mkurnalobis xangrZlivobis Semcireba zrdis mkurnalobisadmi damyolobas;
 amcirebs wyvetili mkurnalobis SemTxvevebs;
 axdens rezistentobis ganviTarebis prevencias (qinolonebi???);
 Moxi-is
gamoyeneba SeiZleba ARV mkurnalobis pirobebSi, vinaidan
R-sgan gansxvavebiT mcired axdens citoqrom P-450 fermentis
inducirebas;
 izoniazidis
Moxi-iT Canacvleba TB maRali tvirTis mqone qveynebSic
SesaZlebels gaxdis LTBI-s H-iT mkurnalobas.
uaryofiTi Tu dadebiTi Sedegebi???
 samkurnalo
reJimSi moqsifloqsacinis CarTva, xangrZlivobis
Semcirebis miuxedavad, gamoiwvevs mkurnalobis xarjebis
gazrdas;
nacionaluri programebis umetesobas danaxarjis gazrda
gamarTlebulad miaCnia.
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.
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.


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
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.

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.
gmadlobT
yuradRebisaTvis