Shaanxi BLOOM Tech Co., Ltd. yog ib qho ntawm cov tuam ntxhab thiab cov muag khoom ntawm imatinib cas 152459-95-5 hauv Suav teb. Txais tos rau cov lag luam wholesale bulk zoo imatinib cas 152459-95-5 muag ntawm no los ntawm peb lub hoobkas. Kev pabcuam zoo thiab tus nqi tsim nyog muaj.
Imatinib, tseem hu ua mesylate, yog ib qho me me molecule protein kinase inhibitor, tshwj xeeb tshaj yog tyrosine kinase inhibitor, uas muaj peev xwm los thaiv ib los yog ntau dua protein kinases. Nws yog dawb crystalline hmoov, CAS 152459-95-5, molecular mis C29H31N7O, thaum cov tshuaj formula ntawm mesylate yog C30H35N7O4S, uas yog nws daim ntawv methanesulfonate ntsev. Ob leeg nyob rau hauv vitro thiab hauv vivo, nws muaj zog inhibits kev ua ntawm ABL tyrosine kinase, tshwj xeeb tshaj yog suppressing kev qhia ntawm ABL thiab proliferation ntawm BCR-ABL hlwb.
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Tshuaj Formula |
C29H31N7O |
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Exact Mass |
493 |
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Molecular Luj |
494 |
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m/z |
493 (100.0%), 494 (31.4%), 495 (2.7%), 494 (2.6%), 495 (2.0%) |
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Elemental Analysis |
C, 70.56; H, 6.33; N, 19.86; O, 3.24 |
Tsis tas li ntawd, nws tuaj yeem cuam tshuam tyrosine kinases ntawm platelet - tau txais txiaj ntsig kev loj hlob (PDGF) thiab qia cell factor (SCF) receptors, yog li inhibiting biochemical cov tshuaj tiv thaiv los ntawm cov xwm txheej no. Nws muaj cov teebmeem thiab kev ua haujlwm ntawm inhibiting tyrosine kinase, inhibiting cell proliferation, inhibiting qog loj hlob, prolonging ciaj sia taus, thiab txhim kho cov neeg mob lub neej zoo. Nws tuaj yeem thaiv cov kauj ruam tseem ceeb hauv txoj kev taw qhia, yog li inhibiting cell proliferation. Inhibiting cell proliferation los ntawm kev cuam tshuam nrog kev ua haujlwm ntawm cell cycle regulatory factor kom ua tiav cov hom phiaj kho mob. Cov tshuaj tua kab mob ntawm cov khoom no tuaj yeem xaiv inhibit qhov kev ua haujlwm ntawm cov proteins tshwj xeeb, yog li tswj kev loj hlob ntawm cov qog hlwb. Cov khoom no tsuas yog siv rau hauv chav kuaj thiab raug txwv nruj rau lwm lub hom phiaj.
Imatinib, tseem hu ua imatinb mesylate, yog ib qho tseem ceeb los tiv thaiv -cov tshuaj qog nqaij hlav uas ua lub luag haujlwm tseem ceeb hauv kev kho mob leukemia. Raws li cov protein tshiab tyrosine kinase inhibitor, nws tuaj yeem thaiv cov teeb liab hloov pauv hauv cov hlwb leukemia, yog li ua tiav cov hom phiaj kho mob.
CML yog ib qho mob qog noj ntshav uas cuam tshuam rau tiam ntawm cov pob txha pob txha cov ntshav, uas tshwm sim los ntawm qhov txawv txav ntawm cov qe ntshav dawb hauv cov pob txha. Nws yog feem ntau siv ua ntej - kab kev kho rau CML, feem ntau yog los ntawm inhibiting tyrosine kinase kev ua ntawm BCR-ABL fusion protein.
BCR-ABL fusion protein yog tsim los ntawm Philadelphia chromosome abnormalities thiab plays lub luag haujlwm tseem ceeb hauv cov kab mob ntawm CML. Imatinb tuaj yeem khi rau BCR-ABL kinase domain, thaiv nws txoj haujlwm tyrosine kinase, tiv thaiv kev ua kom tsis muaj zog ntawm cov teeb liab hloov, thiab yog li inhibit qhov kev loj hlob thiab kev faib tawm ntawm cov hlwb malignant.
Nyob rau hauv kev kho mob ntawm zoo mob lymphoblastic leukemia (ALL)
Nws kuj muaj qee yam kev kho mob. Tshwj xeeb tshaj yog rau refractory TAG NRHO cov neeg mob nqa cov fusion genes tshwj xeeb, xws li RCSD1-ABL1 fusion gene, imatinb tuaj yeem cuam tshuam kev ua haujlwm ntawm BCR-ABL kinase, txo qhov kev loj hlob thiab ciaj sia ntawm tag nrho cov hlwb zoo, yog li txhim kho cov kab mob kev loj hlob thiab kev kwv yees ntawm cov neeg mob.
Muaj cov ntaub ntawv tshaj tawm qhia tias kev siv imatinb monotherapy tuaj yeem muab kev pab cuam ib nrab rau cov neeg mob uas muaj refractory ALL, tsim kom muaj kev kho mob tom ntej. Tsis tas li ntawd, imatinb kuj tuaj yeem siv ua ke nrog lwm txoj kev kho mob, xws li chimeric antigen receptor T-cell therapy (CAR-T), txhawm rau txhim kho kev kho mob zoo.
Nws kuj muaj qee qhov kev thov nqi. GIST yog cov qog hlav tawm los ntawm cov ntaub so ntswg mesenchymal ntawm txoj hnyuv, thiab imatinb tuaj yeem siv ua thawj - kab kev kho mob rau GIST. Nws txo cov qog cell proliferation thiab ciaj sia los ntawm inhibiting cov kev ua ntawm ob tyrosine kinases, KIT thiab PDGFRA, yog li tswj cov qog loj thiab ncua cov kab mob. Imatinb yog ib qho kev kho mob zoo rau cov neeg mob GIST malignant uas tsis tuaj yeem raug phais phais lossis twb tau tsim cov metastasis nyob deb.
Txawm li cas los xij, nws tsim nyog sau cia tias imatinb kuj tuaj yeem ua rau qee qhov kev mob tshwm sim hauv kev kho mob leukemia. Cov kev mob tshwm sim feem ntau muaj xws li xeev siab, ntuav, raws plab, ua pob liab vog, qaug zog, thiab lwm yam. Tsis tas li ntawd, imatinb kuj tseem tuaj yeem ua rau pob txha pob txha, ua rau cov qe ntshav dawb thiab platelets txo. Yog li ntawd, ua ntej siv imatinb, nws raug nquahu kom sab laj nrog kws kho mob thiab ua raws li lawv cov lus qhia rau kev siv tshuaj. Nyob rau tib lub sijhawm, cov neeg mob yuav tsum tau ua raws li kev soj ntsuam hematological, molecular, thiab cytogenetic soj ntsuam kom raws sij hawm ntsuas kev kho mob kom zoo thiab kuaj xyuas cov kev mob tshwm sim.
Tsis tas li ntawd, nrog rau hauv - kev tshawb fawb tob txog kab mob leukemia thiab nws txoj kev kho mob, daim ntawv thov ntawm imatinb txuas ntxiv nthuav dav thiab ua kom zoo dua qub. Piv txwv li, cov kws tshawb fawb tab tom tsim cov tshiab tyrosine kinase inhibitors (TKIs) kom kov yeej imatinb tsis kam thiab txhim kho kev kho mob kom zoo. Nyob rau tib lub sijhawm, kev sib xyaw ua ke ntawm ntau hom TKIs lossis lwm yam tshuaj tiv thaiv - mob qog noj ntshav tuaj yeem txhim kho kev kho mob thiab ncua qhov tshwm sim ntawm cov tshuaj tiv thaiv. Tsis tas li ntawd, cov tswv yim kho tus kheej yog maj mam ua tau. Los ntawm kev txheeb xyuas tus neeg mob qhov kev hloov pauv spectrum thiab cov yam ntxwv ntawm cov tshuaj metabolism, cov kws kho mob tuaj yeem hloov kho qhov kev npaj kho mob zoo tshaj plaws rau txhua tus neeg mob.
Daim ntawv thov hauv Dermatofibrosarcoma Protuberans (DFSP)
Imatinib yog ib qho tshuaj tseem ceeb rau kev kho mob ntawm dermatofibrosarcoma protuberans (DFSP). Nws cov ntsiab lus tseem ceeb suav nrog cov neeg mob uas tsis tuaj yeem kho tsis tau, rov tshwm sim, lossis metastatic DFSP, tshwj xeeb tshaj yog cov uas tsis tsim nyog rau kev phais vim qhov loj ntawm cov qog, kev cuam tshuam ntawm cov qauv tseem ceeb, lossis muaj kev pheej hmoo siab ntawm kev ua kom zoo nkauj lossis kev ua haujlwm tsis zoo. Cov kev tshawb fawb soj ntsuam tau pom tias kev kho mob nrog imatinib ntawm ib koob tshuaj txhua hnub ntawm 400-800 mg tuaj yeem ua tiav ib feem ntawm cov qog nqaij hlav los yog kab mob stabilization hauv qee cov neeg mob, tsis muaj qhov sib txawv ntawm qhov ua tau zoo ntawm ob qib.
Tsis tas li ntawd, nws tuaj yeem siv los ua kev kho mob neoadjuvant ua ntej kom txo cov qog ntim, yog li tsim kev phais rau cov neeg mob uas pib tsis tuaj yeem kho. Nws yuav tsum tau muab sau tseg tias imatinib yuav tsum tau siv raws li kev qhia ntawm tus kws kho mob, thiab cov kev phiv tshuaj yuav tsum tau saib xyuas thaum kho. Nws siv tau zoo txhim kho qhov kev cia siab ntawm cov neeg mob nrog DFSP siab heev thiab tau dhau los ua qhov kev kho mob tseem ceeb tshaj li kev phais.
Imatinib, also known as Gleevec, is an important anti-tumor drug primarily used to treat chronic myeloid leukemia (CML) and certain types of acute lymphoblastic leukemia (ALL). The commercial synthesis route involves multiple complex chemical steps. The following is a detailed overview of the synthesis steps, but due to space limitations, the specific chemical equations will only provide illustrations of the key steps.
Txheej txheem cej luam ntawm Kev Lag Luam Synthesis Route ntawm Gleevec
Lub synthesis ntawm gleevec feem ntau yog pib los ntawm cov khoom pib tshwj xeeb, mus los ntawm kev sib xyaw thiab kev hloov pauv ntawm ntau qhov nruab nrab, thiab thaum kawg tau txais cov khoom lag luam. Cov hauv qab no yog cov lus piav qhia luv luv ntawm txoj kev sib xyaw ua ke thiab nws cov kauj ruam tseem ceeb:
► Xaiv cov khoom pib thiab cov tshuaj tiv thaiv ua ntej
Chemical Equation Diagram (noj acetylacetone ua piv txwv):
4-methyl-3-nitroaniline + acetylacetone + puag catalyzed → nitroaniline derivatives
Cov ntaub ntawv pib:
Cov khoom pib muaj xws li 4-methyl-3-nitroaniline, 3-acetylpyridine, N, N-dimethylformamide formaldehyde, thiab lwm yam. Cov txheej txheem sib txawv tuaj yeem xaiv cov khoom pib sib txawv.
Cov tshuaj tiv thaiv ua ntej:
Noj 4-methyl-3-nitroaniline ua piv txwv, nws yuav xub tau txais cov tshuaj tiv thaiv condensation thiab hnov mob nrog cov tshuaj carbonyl uas tsim nyog (xws li acetylacetone) los tsim nitroaniline derivatives. Cov kauj ruam no yuav suav nrog alkaline catalysis, xws li siv cov poov tshuaj carbonate lossis sodium hydroxide.
► Txo cov tshuaj tiv thaiv
Daim duab kab zauv sib npaug: nitroaniline derivative + hlau hmoov / HCl + txo → amino aniline derivative
Lub Hom Phiaj:
Txhawm rau txo nitro rau amino, uas yog ib qho ntawm cov kauj ruam tseem ceeb hauv kev sib txuas ntawm Gleevec.
Cov kev mob tshwm sim:
Feem ntau nqa tawm nyob rau hauv lub xub ntiag ntawm hlau catalysts xws li hlau hmoov, stannous chloride, los yog platinum carbon, siv acidic los yog alkaline xov xwm.
► Ntiv nplhaib
Chemical equation diagram (noj hypothetical intermediate ua piv txwv): Aminoaniline derivative + tsim nyog carbonyl compound + cyclization → pyrimidine nplhaib intermediate
Lub hom phiaj:
Los tsim ib lub nplhaib pyrimidine, uas yog ib feem ntawm cov qauv molecular ntawm Gleevec.
Cov kev mob tshwm sim:
Feem ntau yuav tsum tau cua sov thiab tsim nyog catalysts xws li sulfuric acid los yog phosphoric acid.
► Cov tshuaj tiv thaiv Acylation
Daim duab sib npaug tshuaj: pyrimidine nplhaib intermediate + acyl chloride + puag catalysis → acylation intermediate
Lub Hom Phiaj:
Txhawm rau qhia acyl pawg ntawm lub nplhaib pyrimidine hauv kev npaj rau cov tshuaj tiv thaiv tom ntej.
Cov kev mob tshwm sim:
Siv acyl chloride los yog anhydride nyob rau hauv alkaline tej yam kev mob.
► Condensation thiab hloov cov tshuaj tiv thaiv
Chemical equation schematic: Acylation intermediate+N-methylpiperazine+condensation/substitution → Gleevec skeleton
Lub Hom Phiaj:
Txhawm rau condense acylated intermediates nrog amine compounds xws li N-methylpiperazine thiab ua cov tshuaj hloov pauv ntawm txoj haujlwm tsim nyog los tsim cov qauv pob txha ntawm Gleevec.
Cov kev mob tshwm sim:
Feem ntau rhuab nyob rau hauv ib qho hnyav, catalyst yuav tsum tau.
► Cov tshuaj tiv thaiv ntsev tsim
Chemical Equation Diagram: Gleevec skeleton + methanesulfonic acid + ntsev tsim → Gleevec methanesulfonate
Lub Hom Phiaj:
Txhawm rau hloov cov txheej txheem pob txha ntawm Gleevec rau hauv nws daim ntawv methanesulfonate, uas yog Gleevec methanesulfonate, uas yog daim ntawv siv tshuaj kho mob.
Cov kev mob tshwm sim:
Ua los ntawm cov kua qaub- cov tshuaj tiv thaiv hauv paus hauv qhov muaj methanesulfonic acid.
Ib txoj kev synthesis ntawmimatinib.
Cov txheej txheem synthesis siv 4-hydroxymethyl-N-[4-methyl-3-aminophenyl] benzamide ua raw khoom thiab cyanamide ntxiv kom tau txais cov intermediate 4-hydroxymethyl- benzamide (3-phenyl-methyl) Intermediate (II) yog condensed nrog 3-(3-dimethylaminopropynyl) pyridine kom tau nruab nrab 4-hydroxymethyl-N-[4-methyl-3-[4-(3-pyridine)-2-pyrimidine] amino] phenyl] benzamide (III). Intermediate (III) reacts nrog hloov benzenesulfonyl chloride kom tau nruab nrab 4-[substituted benzenesulfonyl methyl]-N-[4-methyl-3-[4-(3-pyridine)-2-pyrimidine] amino] phenyl] benzamide. Thaum kawg, nruab nrab (IV) reacts nrog methyl piperazine kom tau Gleevec (V). Txoj kev no muaj cov txheej txheem yooj yim, mob me me, cov khoom lag luam siab purity, siab tawm los, tsis tshua muaj nqi, thiab yog qhov tsim nyog rau kev tsim khoom lag luam.
Cov kauj ruam ntxaws ntxaws thiab tshuaj sib npaug rau kev sib txuas ntawm Gleevec
Raw khoom: 4-hydroxymethyl-N-[4-methyl-3-aminophenyl] benzamide
Reagent: Monocyanamide
Qhov xwm txheej: Feem ntau, qhov tsim nyog ntawm cov kua qaub (xws li hydrochloric acid) yog ntxiv los ua ib qho catalyst nyob rau hauv cov kua aqueous, thiab rhuab mus rau qhov kub thiab txias (xws li 60-80℃C) rau cov tshuaj tiv thaiv.
Cov lus piav qhia cov tshuaj tiv thaiv: Hauv cov kauj ruam no, pawg amino ntawm 4-hydroxymethyl-N-[4-methyl-3-aminophenyl] benzamide tau txais cov tshuaj tiv thaiv ntxiv nrog rau pawg cyanide ntawm cyanamide, tsim ib pab pawg guanidine.
Chemical Equation:
4-Hydroxymethyl-N-[4-methyl-3-aminophenyl] benzamide+melamine → 4-hydroxymethyl-N-(3-guanidino-4-methylphenyl) benzamide + dej
Raw Khoom: 4-Hydroxymethyl-N-(3-Guanidino-4-methylphenyl) benzamide (Intermediate II)
Reagent: 3-(3-dimethylamino-allyl) pyridine
Qhov xwm txheej: Ntxiv ib lub hauv paus tsim nyog (xws li triethylamine) ua cov catalyst hauv cov kuab tshuaj inert (xws li N, N-dimethylformamide DMF) thiab ua kom sov cov tshuaj tiv thaiv hauv qab reflux.
Cov lus piav qhia cov tshuaj tiv thaiv: Cov pab pawg guanidine ntawm nruab nrab II tau txais cov tshuaj tiv thaiv condensation nrog rau pawg allyl ntawm 3-(3-dimethylamino-allyl) pyridine los ua ib lub nplhaib pyrimidine.
Kev sib piv tshuaj: 4-hydroxymethyl-N-(3-guanidino-4-methylphenyl) benzamide+3-(3-dimethylaminopropynyl) pyridine → 4-hydroxymethyl-N-[4-methyl-3-pyri][4-methyl-3-pyri] phenyl] benzamide + byproduct
Nco tseg: Cov khoom los ntawm - ntawm no tuaj yeem suav nrog dimethylamine, dej, thiab lwm yam, nyob ntawm seb cov tshuaj tiv thaiv thiab kev xaiv catalyst.
Raw khoom: 4-hydroxymethyl-N-[4-methyl-3-[[4-(3-pyridine)-2-pyrimidine] amino] phenyl] benzamide (intermediate III)
Reagent: hloov benzenesulfonyl chloride (xws li 4-chlorobenzenesulfonyl chloride)
Qhov xwm txheej: Ntxiv qhov tsim nyog ntawm lub hauv paus (xws li triethylamine lossis pyridine) ua cov kua qaub khi rau hauv cov kuab tshuaj inert (xws li dichloromethane), tswj cov tshuaj tiv thaiv kub hauv cov dej khov ntsev da dej, thiab maj mam nce qhov kub ntawm chav tsev kub lossis siab dua me ntsis.
Cov lus piav qhia Cov tshuaj tiv thaiv: Cov pab pawg hydroxymethyl ntawm nruab nrab III tau hloov pauv cov tshuaj tiv thaiv nrog sulfonyl chloride pawg ntawm cov tshuaj hloov benzenesulfonyl chloride, tsim ib pab pawg methyl sulfonate.
Kev sib npaug tshuaj: 4-hydroxymethyl-N-[4-methyl-3-[4-(3-pyridine)-2-pyrimidine] amino] phenyl] benzamide + hloov benzenesulfonyl chloride → 4-[subestonic acid ester]-N-[4-methyl-3-[4-(3-pyridine)-2-pyrimidine] amino] phenyl] benzamide + hydrogen chloride
Raw khoom: 4-[substituted benzenesulfonic acid methyl ester]-N-[4-methyl-3-[[4-(3-pyridine)-2-pyrimidine] amino] phenyl] benzamide (intermediate IV)
Reagent: Methylpiperazine
Mob: Thaum tshav kub kub thiab reflux cov tshuaj tiv thaiv nyob rau hauv ib tug haum hnyav (xws li ethanol los yog isopropanol), thaum ntxiv ib tug me me ntawm cov kua qaub (xws li hydrochloric acid) rau catalysis.
Cov lus piav qhia Cov tshuaj tiv thaiv: Cov sulfonic acid methyl ester pawg ntawm nruab nrab IV yog hydrolyzed nyob rau hauv acidic tej yam kev mob los tsim ib pab pawg neeg sulfonic acid, uas tom qab ntawd undergoes ib ntsev tsim cov tshuaj tiv thaiv nrog cov amino pawg ntawm methyl piperazine kom tau Gleevec.
Kev sib piv tshuaj: 4-[substituted benzenesulfonate methyl ester]-N-[4-methyl-3-[[4-(3-pyridine)-2-pyrimidine] amino] phenyl] benzamide+methylpiperazine+acid catalyst → Gleevecide
Qhov zoo ntawmImatinibTxoj kev Synthesis
Cov tshuaj tiv thaiv me me
Thoob plaws hauv tag nrho cov txheej txheem synthesis, feem ntau cov tshuaj tiv thaiv tau ua nyob rau hauv cov mob me me, xws li chav tsev kub mus rau nruab nrab qhov kub thiab txias, tsis tas yuav tsum muaj qhov kub thiab txias siab. Qhov no tsis yog tsuas yog muaj txiaj ntsig zoo rau kev tswj cov txheej txheem tshuaj tiv thaiv thiab txo cov tiam los ntawm - cov khoom, tab sis kuj pab tiv thaiv kev ruaj ntseg ntawm cov reactants thiab intermediates.
High purity khoom
Los ntawm cov txheej txheem sib xyaw ua ke thiab cov txheej txheem purification tsim nyog xws li crystallization, recrystallization, kem chromatography, thiab lwm yam., siab -cov khoom purity tuaj yeem tau. Cov khoom purity siab yog qhov tseem ceeb rau kev ua tau zoo thiab kev nyab xeeb ntawm cov tshuaj.
Yooj yim
Txoj kev hluavtaws no muaj qee qhov kev hloov pauv tau yooj yim thiab tuaj yeem hloov kho kom haum raws li kev xav tau ntawm kev lag luam thiab kev tsim khoom. Piv txwv li, Gleevec derivatives nrog cov khoom siv sib txawv tuaj yeem ua ke los ntawm kev hloov hom benzenesulfonyl chloride hloov pauv kom tau raws li qhov xav tau kev kho mob sib txawv.
Pharmacological teebmeem:
Cov khoom no yog ib tug derivative ntawm phenylalanine thiab belongs rau ib tug tshiab tyrosine kinase inhibitor. Kwv yees li 95% ntawm cov neeg mob mob myeloid leukemia (CML) yog pH chromosome zoo, txhais tau hais tias oncogene ABL ntawm chromosome 9 yog ectopic mus rau ib ntu ntawm oncogene ntawm chromosome 22 hu ua breakpoint clustering region (BCR). Ob lub noob sib txuas ua ke los tsim cov fusion protein p-210, uas muaj ntau dua tyrosine kinase kev ua piv rau cov C-ABL protein p-150 thiab tuaj yeem tsim cov leukocyte proliferation, ua rau mob leukemia. Cov khoom no muaj zog tiv thaiv kev ua haujlwm ntawm ABL tyrosine kinase ob leeg hauv vitro thiab hauv vivo, tshwj xeeb tshaj yog txwv kev qhia ntawm ABL thiab kev loj hlob ntawm BCR-ABL hlwb, ua rau nws tsim nyog rau kev kho mob ntawm CML. Tsis tas li ntawd, cov khoom no tuaj yeem cuam tshuam cov tyrosine kinases ntawm platelet-derived growth factor (PDGF) thiab qia cell factor (SCF) receptors, thiab tuaj yeem cuam tshuam cov tshuaj lom neeg biochemical mediated los ntawm PDGF thiab SCF, tab sis tsis cuam tshuam rau lub teeb liab hloov ntawm lwm yam stimulating yam xws li epidermal kev loj hlob.
Cov tshuaj sib cuam tshuam
► Cov tshuaj uas tuaj yeem hloov cov ntshav plasma concentration ntawm Gleevec
CYP3A4 inhibitor: Tom qab noj ib koob tshuaj ketoconazole (CYP3A4) inhibitor hauv cov neeg noj qab haus huv, cov tshuaj raug rau Gleevec nce ntxiv (txhais tau tias qhov siab tshaj plaws ntshav siab (Cmax) thiab thaj tsam hauv qab Gleevec nkhaus (AUC) nce 26% thiab 40%, feem). Tsis muaj kev paub txog kev tswj hwm nrog lwm cov CYP3A4 inhibitors xws li itraconazole, erythromycin, thiab clarithromycin.
CYP3A4 inducer: Tom qab cov neeg ua haujlwm noj qab haus huv tau noj rifampicin, qhov kev tshem tawm ntawm Gleevec tau nce 3.8 npaug (90% kev ntseeg siab ib ntus=3.5-4.3 zaug), tab sis Cmax, AUC (0-24), thiab AUC (0-8) txo los ntawm 54%, 68%, thiab 74%, feem. Hauv kev tshawb fawb soj ntsuam, nws tau pom tias kev tswj hwm ib txhij ntawm phenytoin ua rau txo qis hauv plasma concentration ntawm Gleevec, uas ua rau txo qis kev ua tau zoo. Cov txiaj ntsig zoo sib xws tau pom hauv cov neeg mob glioma uas tau kho nrog enzyme induced anti epileptic deus (EIAEs) xws li carbamazepine, oxcarbazepine, phenytoin, phosphophenytoin, phenobarbital, thiab phenobarbital. Piv nrog rau kev noj EIAEDs ntawm lub sijhawm sib txawv, AUC ntawm Gleevec tau txo qis rau 73%. Lwm yam CYP3A4 inducers xws li dexamethasone, ketamine, phenobarbital, thiab lwm yam yuav muaj teeb meem zoo sib xws, yog li kev siv ib txhij ntawm Gleevec thiab CYP3A4 inducers yuav tsum zam. Hauv ob txoj kev tshawb fawb luam tawm, kev sib xyaw ntawm Gleevec thiab St John wort extract formulations ua rau 30-32% txo qis hauv AUC ntawm cov khoom.
► Imatinibmesylate hloov plasma concentration ntawm cov tshuaj hauv qab no
Nws nce qhov nruab nrab Cmax thiab AUC ntawm simvastatin (CYP3A4 substrate) los ntawm 2-fold thiab 3.5-fold, feem. Nws yuav tsum tau muab sau tseg tias Gleevec tsub kom lub plasma concentration ntawm lwm yam tshuaj metabolized los ntawm CYP3A4, xws li benzodiazepines, dihydropyridine, calcium channel antagonists, thiab lwm yam HMG CoA reductase inhibitors. Yog li ntawd, yuav tsum tau ceev faj thaum noj cov tshuaj no thiab CYP3A4 substrates nrog nqaim kho qhov rais (xws li cyclosporine thiab pembrozil) ib txhij.
Ntawm cov concentrations zoo ib yam li cov uas inhibit CYP3A4 kev ua, nws tuaj yeem inhibit CYP2D6 kev ua hauv vitro. Yog li ntawd, thaum noj ib txhij nrog Gleevec mesylate, nws yuav ua rau kom lub cev raug rau CYP2D6 substrates. Txawm hais tias tsis muaj kev tshawb fawb tshwj xeeb tau ua, tau pom zoo kom ceev faj.
Nws tuaj yeem cuam tshuam kev ua haujlwm ntawm CYP2C9 thiab CYP2C19 hauv vitro, thiab lub sijhawm ntev prothrombin tuaj yeem pom tom qab noj warfarin. Yog li ntawd, thaum pib los yog hloov cov koob tshuaj ntawm Gleevec mesylate kev kho mob, luv luv - lub sij hawm soj ntsuam ntawm lub sij hawm prothrombin yuav tsum tau ua yog tias dual coumarin kuj siv.
Cov nyhuv inhibitory ntawm iGleevec 400 mg ob zaug ib hnub ntawm CYP2D6 induced metoprolol metabolism tsis muaj zog, nrog rau Cmax thiab AUC nce ntawm kwv yees li 23% rau metoprolol. Kev sib xyaw ua ke ntawm Gleevec thiab CYP2D6 inducers xws li metoprolol zoo li tsis muaj kev pheej hmoo rau kev sib cuam tshuam tshuaj thiab tsis tas yuav tsum tau hloov tshuaj.
FAQ
Dab tsi yog qhov prognosis rau cov neeg mob imatinib?
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Ntawm cov neeg mob hauv pawg imatinib, kwv yees tag nrho cov ciaj sia taus ntawm 10 xyoo yog 83.3%. Kwv yees li ib nrab ntawm cov neeg mob (48.3%) uas tau random muab rau imatinib ua tiav kev kho mob nrog imatinib, thiab 82.8% muaj cov lus teb cytogenetic tiav.
Cov neeg mob noj imatinib ntev npaum li cas?
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Txhawm rau txo qhov rov tshwm sim thiab txhim kho lub sijhawm ntev - ciaj sia taus, peb xav kom cov neeg mob uas muaj kev pheej hmoo siab GIST tau txais kev kho mob imatinib rauyam tsawg kawg yog 5 xyoo.
Dab tsi yuav tsum zam thaum noj imatinib?
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Grapefruit los yog kua txiv hmab txiv ntoo tuaj yeem cuam tshuam nrog imatinib; tsis txhob noj lossis haus cov no thaum koj kho nrog imatinib. Tham nrog koj tus kws kho mob lossis tus kws muag tshuaj ua ntej noj cov tshuaj tshiab lossis tshuaj ntxiv, lossis tau txais cov tshuaj tiv thaiv. Kho imatinib nrog kev saib xyuas.
imatinib vam meej li cas?
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Ntawm cov neeg mob hauv pawg imatinib, kwv yees tag nrho cov ciaj sia taus ntawm 10 xyoo yog 83.3%. Kwv yees li ib nrab ntawm cov neeg mob (48.3%) uas tau random muab rau imatinib ua tiav kev kho mob nrog imatinib, thiab 82.8% muaj cov lus teb cytogenetic tiav.
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