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ChineseJournalofNewDrugs2015,24(19)216120152419。01088196338E-mailfanliping28@126.com。。01088196206E-mailzyh8812@163.com。··CDK4/6palbociclib12112111001422100191palbocicibCDK4/6CDK4/6。20152FDAER、HER2。。、、、、、、。CDK4/6palbociclibR979.1A1003-3734201519-2161-04AnovelCDK4/6inhibitorpalbociclibFANLi-ping12JIAOYuan-yuan1GUOZi-han12ZHANGYan-hua11KeyLaboratoryofCarcinogenesisandTranslationalResearchMinistryofEducationDepartmentofPharmacyPekingUniversityCancerHospital&InstituteBeijing100142China2DepartmentofPharmacyAdministrationandClinicalPharmacySchoolofPharmaceuticalSciencesPekingUniversityHealthScienceCenterBeijing100191ChinaAbstractPalbociclibisanoralselectiveinhibitorofcyclin-dependentkinaseCDK4and6whichcanrestorethecontrolofcellcycleandblocktheproliferationoftumorcells.InFebruary2015palbociclibwasap-provedbytheacceleratedapprovalprocessoftheUSFDAandindicatedincombinationwithletrozoleforthetreat-mentofpostmenopausalwomenwithestrogenreceptorER-positivehumanepidermalgrowthfactorreceptor2HER2-negativeadvancedbreastcancerasinitialendocrine-basedtherapyfortheirmetastaticdisease.Thedrugisananti-breastcancerdrugofnewmechanismandhasdesirableefficacy.Themainadversereactionisneutrope-nia.Inthisarticlethemechanismpharmacokineticspharmacodynamicsclinicalstudiesdosageandadminis-trationdruginteractionssafetyanduseofpalbociclibinspecificpopulationwerereviewed.KeywordsCDK4/6inhibitorbreastcancerpalbociclib。200813822.9%4613.7%1.7%1。16.912.25%18.22。palbociclibIbrancePfi-zerCDK4/620152FDAestrogenreceptorER、2humanepidermalgrowthfactorreceptorHER2。ChineseJournalofNewDrugs2015,24(19)216220152419progression-freesurialPFS。palbociclibC24H29N7O2447.546--8--5--2-5--1--2--8H-23-D-7-1。1palbociclib1cyclin-dependentproteinkinasesCDKs13CDK1~1312cyclinsA~L。CDKscyclinsDNA。CDKs3。palbociclibCDK4/6。cyclinD1CDK4/6。palbociclibG1SER。palbociclibretinoblastomaproteinRbE2F4。6d。ERRb、5。25palbociclibTmax6~12h。125mg46%。25~225mgAUCCmax。qd8d。2.41.5~4.2。palbociclibpalbociclib。palbociclib85%Vz/F2583L26%CV。palbociclib。14Cpalbociclib。palbociclib2.3%6.9%。palbociclib26%。CYP3ASULT2A1palbo-ciclib。palbociclibCL/F63.1L·h-129%CV29±5h。74.1%17.5%。。35184palbociclibQTc。125mg·d-121d7d28dpalbociclibQTc>20ms。46、、palbociclibER、HER2。1ER、HER22CCND1/p16INK4ACDKN2A。1∶132.5mgqd2.5mgqd+palbociclib125mgqd7d28d。20091222201251216584palbociclib+81。29.695%CI27.9~36.027.925.5~31.1415920.213.8~27.5HR0.48895%CI0.319~0.748one-sidedP=0.000410.295%CI5.7~12.6。ChineseJournalofNewDrugs2015,24(19)2163201524191n=665.72.6~10.5palbociclib+26.111.2~HR0.2990.156~0.572one-sidedP<0.0001。2n=6611.17.1~16.4palbociclib+18.113.1~27.5HR0.5080.303~0.853one-sidedP=0.0046。palbociclib+n=83n=73344554%vs11%1619%vs044%vs11%。palbociclib+34%22%22%。FN。palbociclib+1113%22%。palbociclibER、HER2。55palbociclib12510075mg。125mgqd21d7d。palbociclib。100mg·d-175mg·d-1。75mg·d-1。CTCAEVer-sion4.0123≤23ANC<500~1000·mm-3+≥38.5℃/≤2ANC≥1000·mm-34≤2。CTCAEVer-sion4.012≥3≤2。palbociclibCYP3Apalbociclib75mgqd。CYP3ApalbociclibCYP3A3~5。65palbociclibCYP3ASULT2A1。palbociclibCYP3A、、、、/、、、、、、、、。palbociclib。palbociclibCYP3A、、CYP3A、、、。palbociclib61%。palbociclibCYP3A、、、、、、、、CYP3A。75palbociclib≥10%、、、、、、、、、、、、、、。85①palbociclib。palbociclib2。②palbociclib。③Ibrance。④palbociclib。>1.5×ULNASTpalbociclib。2202ChineseJournalofNewDrugs2015,24(19)220220152419nopharmacol20111382530-536.27XIANGLJIANGPZHANC.TheserummetabolomicstudyofinterventioneffectsofthetraditionalChinesemedicineShexiangBaoxinPillandamulti-componentmedicinepolypillinthetreat-mentofmyocardialinfarctioninratsJ.MolBiosyst2012882434-2442.28LIUYJIAHCHANGXetal.MetabolicpathwaysinvolvedinXin-Ke-Shuprotectingagainstmyocardialinfarctioninratsu-singultrahigh-performanceliquidchromatographycoupledwithquadrupoletime-of-flightmassspectrometryJ.JPharmBiomedAnal20149035-44.29ZHANGFZHANQDONGXetal.ShengxiandecoctioninchronicheartfailuretreatmentandsynergisticpropertyofPlatyc-odonisRadixametabolomicapproachanditsapplicationJ.MolBiosyst20141082055-2063.30XINXZOUHZHENGNetal.MetabonomicstrategytotheevaluationofChinesemedicinecompoundDanshenDrippingPillsinterferingmyocardialischemiainratsJ.Evid-BasedComple-mentAlternatMed20132013718305.doi10.1155/2013/718305.31CHENYTANGYZHANGYCetal.AmetabolomicstudyofratswithDoxorubicin-inducedcardiomyopathyandshengmaiin-jectiontreatmentJ.PLoSOne2015105e125209.32.D.2011.33LVYLIUXYANSetal.MetabolomicstudyofmyocardialischemiaandinterventioneffectsofCompoundDanshenTabletsinratsusingultra-performanceliquidchromatography/quadrupoletime-of-flightmassspectrometryJ.JPharmBiomedAnal2010521129-135.34LUYLIUXLIANGXetal.MetabolomicstrategytostudytherapeuticandsynergisticeffectsoftanshinoneIIAsalvianolicacidBandginsenosideRb1inmyocardialischemiaratsJ.JEthnopharmacol2011134145-49.35GUONYANGDWANGXetal.Metabonomicstudyofchro-nicheartfailureandeffectsofChineseherbaldecoctioninratsJ.JChromatogrA2014136289-101.36.J.2013328613-617.37MINGQSJIANXLCHENGRLetal.MetabonomicsstudyofTCMformulaQutanHuayuTongmaiGranuleasaneffectivetreatmentforatherosclerosisinmini-pigsJ.Chromatographia20127521-221279-1286.38YANBDENGYHOUJet
本文标题:新型CDK4_6抑制剂palbociclib_范丽萍
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