Chiropa s9 chidimbu: Kubudirira mukuwana zvinodhaka & s9 metabolic kugadzikana

Mazwi Akakosha:Chiropa S9 Chikwangwani, HEPTIC S9 chidimbu, LUNGS SLOCAT, TOLLE FLICT SLECACTION, ADME, LIMVL STUL STUBALISM Kugadzikana, chidimbu chidimbu

1 zvigadzirwa zvePhepase

2 mu vitro zvinodhaka metabolism kugadzikana kudzidza

Mu vitro metabolic kugadzikana kutsvagisa kuidza iyo biotransformation mwero muzvikamu zvemhandozi zvakadai sechipiriso chemhando, kuti uratidze mukana wePK yeVivo uye zuva reAdme, Shamisa yekutanga - Kuburitsa kuongorora makomendi, uye kufanotaura huwandu hwevanhu clearance. Sekureva kwaFDA Mitemo,mu vitro zvinodhaka metabolismZvidzidzo zvinoda kushandiswa kwekuratidzira kwekuratidzira kwemuchato wemunhu wemufananidzo (Hlm), chiropa chevanhu chando (uye cytochrome p450 enzymes (mu vitro) kuti uone maitiro ezvivakwa.

3 chiropa S9 chidimbu / hepatic s9 chidimbu

The thechiropa s9 chidimbu (Hepatic S9 chidimbu)Mitochondria yemahara Supernatant yemugove wechiyero cell cell homogenate, ane nhamba huru yemitambo uye mamwe mishonga yedhisheni enzymes. Ichi chishandiso chinonyanya kubatsira chekufunda metabolism yemishonga yemakomisheni uye kuongorora zvinowanikwa zvinodhaka - kutungamirwa kwezvinodhaka. Izvo zvakare zvakakosha kuongororwa kweTogue yeTogue yeTeguenicity bvunzo (ames) uye ne chromoomac testation bvunzo (ca) mune zvinodhaka, chikafu, makemikari, mishonga, mishonga yekuuraya zvipuka, uye imwe mishonga. Mune metabolic kugadzikana bvunzo, chiropa s9 chinonyanya kushandiswa munzvimbo dzinotevera:

Resentent Clearance Rate: Ichi chiratidzo chakakosha chekuongorora metabolic enzyme chiitiko mukugadzirira chiropa S9 gadziriro. Semuenzaniso, mumuviri wemunhu, iyo intrinsic clearance clear yeropa s9 inenge 634, ichiratidza kuti chiropa s9 ine hunyanzvi hwekuita mitezo.

Metabolite Kuzivikanwa: Chikwereti S9 Chinogona Kuita Metabolize Yakasiyana-siyana Compounds uye gadzira akasiyana metabolites. Iko kuzivikanwa kweaya metabolites kwakakosha kuti unzwisise nzira ye metabolic uye zviitiko zvingangoita zvinodhaka.

Metabolic phenotype research: inosanganisira yavo metabolic chiyero uye zvinogoneka zvekudyidzana, zvinogona kudzidza kuburikidza nekugadzirira chiropa S9.

4 mudumbu s9 chidimbu

Danho remukati s9 chinhu chinyowani /chidimbu chidimbuKugadzirira kubva mumhirizhonga yemukati, ine zvakawanda zvinodhaka metabolizing enzymes (senge cyp3a4, ugt, sult) uye puroteni yekutakura. Izvo zvinonyanya kushandiswa kudzidza yekutanga - Pass metabolism yemuromo mishonga uye synergistic mhedzisiro yemukati yekutambisa metabolism. Zvikumbiro zvayo zvinosanganisira kuongorora biotransformation yezvinodhaka mugut (yakadai seyekusagadzikana kana gluuronidication), kuratidza mupiro wejongwe metabolic enzymes (senge sult1b1).

5 zvimwe zvidimbu zvemukati

LUNG S9, INTNEY S9, uye Ganda S9 inotorwa kubva kuChidimbu Tishu uye yakashandiswa kudzidza metabolism uye chinangwa nhengo yechidimbu.

Lung S9 chidimbu.

Kidney S9 chidimbu.

Ganda s9 chidimbu: Dzidza metabolic kugadzikana kwetransdermal zvinodhaka uye activation yeganda enzymes (senge sult1e1).

Izvi zvikamu zveS9

6 Mhando dzakasiyana ROPA S9 chidimbu

Iyo metabolic activation system mune genetic yekuyera kuongororwa mhinduro yakasanganiswa yeropa s9 uye cofgers yakagadzirirwa kubva kune mhuka chiropa mushure mekuita zvinodhaka. Parizvino, misiyano mu metabolic kugadzikana uye metabolite profiles pakati pemarudzi akasiyana anowanzoenzaniswa neye vitro microurroses, masero echipfuva, chiropa, chiropa s9, uye plasma. Mhando dzebhandi uye dzisiri - dzimba dzemhando dzine mafambiro epakutanga metabolic kuvanhu vakasarudzwa. Naizvozvo, mukusarudzwa kwezvinhu zvekuedza zvechiropa S9, izvo zvinowanzoitika zvinosanganisirachiropa chevanhu s9 smo, monkey chiropa s9 chidimbu, beagle imbwa chiropa s9 chidimbu, rat chiropa s9 chidimbu,uyembeva chombo s9 chidimbu

7 Mhedziso

Izvo zvikamu zveS9 (zvinosanganisira chiropa s9, lung s9, itsvo uye ganda s9) dzinotsvaga dhizaini rekushanda kweVitro mukuratidzira kwe enzyme basa uye metabolic mamiriro ematisiki akasiyana. Chiropa S9, neImafu Akapfuma Metabolic enzymed akadai seCits uye maalts, anoshandiswa zvakanyanya nekuda kwekutsunga kwemarara, metabolite kuzivikanwa, uye nekudyidzana kwekutaurirana nemishonga; Mbiri S9 inotarisa pane yekutanga Pass metabolism uye kutumira metabolism synergy yemiova mishonga; Uye Lung S9, itsvo s9, uye ganda S9 inogona kuongorora chinangwa chinangwa cheterlism chaiyo uye nechetura, kuzadza zvisizvo zvechiropa metabolism mhando. Mukuwedzera, fananidzira zvidzidzo zvakapfuura marudzi eS9 (sengechiropa chevanhu s9 chidimbu, Monkey S9 chidimbu, Beagle imbwa S9 chidimbu, rat s9 chidimbu) chinogona kubatsira kusarudza iyo yakanakisa muenzaniso wekuedza uye kusimudzira kukosha kwekushandurwa kwedata.