Nilotinibyog txhim kho los ntawm cov qauv molecular ntawm imatinib, uas muaj zog xaiv rau BCR-ABL kinase kev ua, thiab nws inhibition ntawm tyrosine kinase yog 30 npaug zog dua imatinib, thiab nws muaj peev xwm inhibit kinase kev ua ntawm imatinib-resistant BCR-ABL mutant. Tib lub sijhawm, nws tuaj yeem cuam tshuam KIT thiab PDGFR kinase kev ua haujlwm.
Cov neeg mob CML tau kho nrog nilotinib 50-1200 mg QD lossis 400-600 mg bid. Lub sijhawm siab tshaj plaws yog 3 teev. Tom qab kev tswj hwm tas li rau 8 hnub, cov ntshav siab tau mus txog lub xeev khov kho. Lub xeev khov kho C. ntawm 400mg bid yog 3.6 wmol · L ~; Kev tshem tawm ib nrab-lub neej yog 15 h, thiab lub xeev ruaj khov AUC yog 2 zaug (QD) thiab 3.8 zaug (kev twv) ntau dua li thawj thawj tswj hwm. Lub ntsiab metabolic txoj kev ntawm nilotinib yog oxidation thiab hydroxylation. Nws tsuas yog muaj nyob rau hauv daim ntawv ntawm kev siv tshuaj nyob rau hauv cov ntshav, thiab nws cov metabolites tsis muaj kev lom zem. Tom qab tau txais ib koob tshuajnilotinibHauv cov neeg ua haujlwm noj qab haus huv, ntau dua 90% ntawm cov khoom raug tso tawm los ntawm cov quav hauv 7 hnub, ntawm 69% yog thawj daim ntawv ntawm cov tshuaj.
Hauv kev sim tshuaj, tom qab kev kho mob nrog Tassigna, 42% ntawm cov neeg mob nrog Philadelphia chromosome zoo (Ph +) CML nyob rau hauv lub sij hawm ntev resistant rau Glivec yuav muaj cov chromosome txawv txav los yog ploj mus; Nyob rau theem nrawm, 31% ntawm cov neeg mob tuaj yeem ua tiav cov txiaj ntsig zoo ib yam.
Raws li qhov tseem ceeb ntawm theem II kev tshawb fawb soj ntsuam, ntsuas qhov txiaj ntsig zoo ntawm kev sim tshuaj ntsuam xyuas ntawm nilotinib qhov ncauj npaj tawm tsam imatinib mesylate lossis hauv kev kho cov neeg mob uas pom tseeb toxicity hauv qeeb thiab nrawm Ph + CML: kev ua haujlwm siab, kev ua siab ntev thiab tswj tau kev nyab xeeb. Thawj thawj zaug hauv ntiaj teb, Switzerland tau pom zoo Novartis' lub zog thiab tshiab tsom rau cov tshuaj kho mob nilotinib qhov ncauj ntsiav tshuaj (lub npe lag luam: Tassigna) kom tau teev rau kev kho mob qog noj ntshav mob qog noj ntshav myeloid leukemia (CML) uas yog ineffective los yog intolerable rau imatinib mesylate (lub npe lag luam: Glivec).
Hauv vitro, nilotinib yog qhov sib tw inhibitor ntawm CYP3A4, cyp2c8, CYi> 2C9, CYP2D6 thiab ugtlal, uas tuaj yeem ua rau kom muaj zog ntawm cov tshuaj tshem tawm los ntawm cov enzymes no. Cov khoom no yog metabolized los ntawm CYP3A4. Lub zog inhibitor lossis inducer ntawm CYP3A4 tuaj yeem nce lossis txo qhov concentration ntawm nilotinib. Cov khoom no kuj yog lub substrate ntawm P-glycoprotein. Thaum cov khoom no ua ke nrog cov tshuaj uas inhibit P-glycoprotein, cov ntshav concentration ntawm nilotinib yuav nce.