Mob siab s9 feem ntawm daim yeeb tshuaj: Kev ua yeeb yam hauv Tshuaj Pom Kev Tshuaj & S9 metabolic ruaj khov

Ntsiab lus:Mob siab s9 feem ntau, hepatic s9 feem, plab tawv nqaij s9 feem, nqaij daim siab s9 feem, lub siab s9 fitt, Tawv S9 Feem, S9 metabolic ruaj khov, subcellular feem

1 Iphase cov khoom

2 Hauv Vitro Tshuaj Yeeb Metabolism Kev Kawm Ruaj Khwv

Nyob rau hauv vitro metanced kev tshawb fawb yog hais txog kev ntsuas biotransform ntawm cov neeg sib txuas lus zoo xws li daim siab matacrices, txhawm rau kom muaj kev cuam tshuam rau hauv vivial hauv vivo thiab hnub ntawmNtxias, ua tiav thaum lub siab siab - los ntawm kev ntsuas ntawm cov tebchaw, thiab kwv yees tib neeg kev txiav txim siab. Raws li FDA cov cai,Hauv cov metro tshuaj metabolismCov kev tshawb fawb yuav tsum tau siv cov kev qhia txog ntawm tib neeg lub siab micromomes (tshiab lossis khov (hauv vitro) los txiav txim siab tib neeg cov kev me me.

3 daim siab s9 feem hauv / hepatic s9 feem

TusMob siab s9 feem (Hepatic S9 Feem)Yog mitochondria dawb supernatant ntawm daim siab parenchymal cell homogenate, muaj ntau cov cyps thiab lwm yam tshuaj metabolizing enzymes enzymes enzymes enzymes enzymes enzymes enzymes enzymes enzymes enzymes enzymes enzymes enzymes enzymes thiab lwm cov tshuaj metabolizing. Nws yog cov cuab yeej tshawb nrhiav tau heev rau kev kawm cov metab metabolism hauv cov tshuaj sib txuas thiab tshawb xyuas cov tshuaj muaj peev xwm tshuaj - Cov kev sib cuam tshuam. Nws tseem yog ib qho kev ntsuas tseem ceeb rau kev ntsuam xyuas kev ntsuam xyuas ntawm kev sib tsoo (CA) Hauv metabolic kev ntsuas kev ruaj khov, nplooj siab s9 yog siv nyob rau hauv cov chaw hauv qab no:

Qhov ntsuas kev tshem tawm tus nqi: Qhov no yog qhov tseem ceeb rau kev ntsuas metabolic enzyme kev ua hauv daim siab s9 npaj. Piv txwv li, hauv tib neeg lub cev, qhov kev tshem tawm tus nqi ntawm daim siab s9 yog kwv yees li ntawm lub siab.

Me meolite tus kheej: Mob siab S9 kev npaj tuaj yeem ua tau metabolize ntau yam sib txuas thiab tsim cov metabolites sib txawv. Kev txheeb xyuas ntawm cov metabolites yog qhov tseem ceeb rau kev nkag siab cov kev ua yeeb yam metabolic thiab cov kev ua yeeb yam ntawm cov tshuaj.

Kev Tshawb Fawb Pheotype Kev Tshawb Fawb: Qhov kev ruaj khov metabolico ntawm cov tshuaj, suav nrog lawv cov metabololic tus nqi, tuaj yeem kawm tau tshuaj los ntawm daim siab s9 npaj.

4 txoj hnyuv s9 feem

Txoj hnyuv S9 yog cov txheej txheem subcellular) /Subcellular feemprepared from intestinal tissue, containing abundant drug metabolizing enzymes (such as CYP3A4, UGT, SULT) and transport proteins. Nws yog tsuas yog siv los kawm ua ntej - hla kev siv tshuaj thiab cov nyhuv synergistic ntawm plab hnyuv metabolism. Nws cov ntawv thov suav nrog kev ntsuas cov tshuaj biotransformation hauv plab (xws li sulfation lossis glucuronidation), thiab txheeb xyuas qhov muag ntawm cov pob txha tshwj xeeb cov khoom siv metabolic (xws li sult1b1).

5 Lwm Feem Kev Mob Hlawv

LUNG S9, thiab Tawv S9 yog muab tau los ntawm cov ntaub di ncauj sib tov thiab siv los kawm cov metabolism hauv zos thiab hom phiaj ua haujlwm.

LUNG S9 Feem: muaj CYP1A1 / 2, siv rau kev ntsuas metanolic ntawm cov tshuaj lom neeg lossis ib puag ncig cov pa paug;

Rabe S9 Feem(renal s9 feem kev sib zog): muaj ovt thiab sult, ntsuas kev tshuaj xyuas cov tshuaj tiv thaiv kev ua kom meej thiab tiam Neprotoxic metabolites;

Daim tawv nqaij s9 feem: Kawm cov tshuaj tsis txaus ntseeg ntawm cov tshuaj pauv hluav taws xob ntawm cov tshuaj pauv hluav taws xob thiab kev ua kom cov tawv nqaij enzymes (xws li SULT1E1).

Cov ntaub ntawv s9 ntxiv cov kev txwv ntawm daim siab metabolic cov ntaub ntawv los ntawm simulating so ntswg - ib puag ncig metabolic.

6 sib txawv tus nplooj siab s9 feem

Kev ua yeeb yam metabolic ua kom lub cev hauv kev sim caj ces yog ib qho kev sib xyaw ntawm lub siab s9 thiab cov celactors npaj los ntawm daim siab tsiaj tom qab tshuaj tiv thaiv tsiaj tom qab tshuaj. Tam sim no, qhov sib txawv hauv metabolic ruaj khov thiab cov metabolite profiles ntawm cov sib txawv ntawm cov kab mob vitro incomes, nplooj siab micrs, nplooj siab s9, thiab ntshav. Cov nas cov tsiaj thiab cov tsiaj tsis muaj - muaj cov cwj pwm ze tshaj plaws rau tib neeg raug xaiv. Yog li ntawd, nyob rau hauv kev xaiv ntawm kev sim cov ntaub ntawv rau daim siab s9, cov uas muaj feem ntau suav nrogTib neeg lub siab s9 feem, Monkey daim siab s9 feem, beagle dev lub siab s9 feem ntau, nas lub siab s9 feem,thiabnas lub siab s9 feem

7 Xaus

Cov txheej txheem S9 (suav nrog lub siab s9, lub raum s9, muab cov ntaub ntawv tseem ceeb rau hauv kev sim tshuaj thiab tawv nqaij thiab tawv nqaij ntawm cov ntaub so ntswg sib txawv. Mob siab s9, nrog nws cov nplua nuj metabolic enzymes xws li dhuav thiab watts, yog dav siv rau intrinsic kev tshem tawm cov kev tshem tawm tus kheej, thiab kev ua yeeb tshuaj sib xws; Cov plab hnyuv S9 tsom rau thawj metabolism thawj zaug thiab nqus tau cov meabolism hauv cov tshuaj noj; Thiab Lung S9, thiab Tawv S9 tuaj yeem ntsuas cov khoom siv metabolism hauv cov metabolism thiab tshuaj lom neeg ntawm daim siab metabolism qauv. Ib qho ntxiv, kev ntsuas sib piv nyob thoob plaws ntawm S9 (xws liNeeg Mob Siab S9 Feem, Monkey S9 Feem, Beagle Aund S9 Feem, nas s9 feem zoo tshaj plaws rau kev sim ua ntej thiab txhim kho tus nqi ntawm cov ntaub ntawv hloov pauv.