药物代谢酶细胞色素P4502C9研究进展

CN3421206PR,ISSN100922501http:PP(6):601-60620032012142004203205863(:2002AA2Z341L),,,:Tel:[phone]E2mail:[e-mail],,,,:Tel:[phone]E2mail:[e-mail]4502C9,1,,266003,;1,100853P4502C9P4502C9,P4502C932P4502C933,P4502C9P4502C9S2P4502C9,P4502C9;;;:R969:A:100922501(2004)0620601206P450(cytochrome,P450),,;[1]P450481P450,22,P450P,35P450,P45012345781117192124275114,13(1)P450P450P450,:1P450P450P%P4503A4P536P4502D619P4502C8P916P4501A1P211P4502C198P4502E14P4502B63P4502A63P45026,AF,P4502C10q24.2[2]P4502CcD2NAsP4502C8P4502C9P4502C10P4502C17P4502C18P4502C19P4502C9,P45020%,P4503AP4502C9,P4502C9,,P4502C931,P4502C932(Arg144Cys)P4502C933(Ilu359Leu)ClyoshiP4502C933P4502C932P4502C9P4502C934(Ile359Thr)P4502C935(Asp360Glu)P4502C936(A818)[3],P4502C91P4502C91983WangP4508,UmbenhauerP4502C9P4502C9106,,1P200,P4502C9,P4502C9P4502C9cDNAsP4502C9cDNAsP4502C9cDNAs490,55.6P4502C9P4502C1992%,43,P4502C9,P4502C9(SRSs),SRSsP4502C996117198205233240286304359369470477P4502C9SRSs,P4502C9SRSs5Ile359Leu,[4]144359,144P4502C92(SRSs),SRS21,144,P4501012,144ArgCys,2R144C359P4502C92(SRSs),P450101b2,Ile359Leu,I359LR144CI359LP4502C92P4502C9P4502C998,55kb,10q24P4502C9,P4502C9,P4502C9522.2kb(GRE)P450BM23(15)P4502C952,P4502C9P4502C9P4502C932,3C430T,Arg144(CGC)Cys144(TGC)P4502C932P4502C931Ava(GGACT),PCRP4502C932P4502C933,7A1075C,Ile359(ATT)Leu359(CTT),NsiPCRP4502C934,,,7T1076C,Ile359(ATT)Thr359(ACT),ApaLPCR7C1080G,Asp360(GAC)Glu360(GAG)P4502C935,,P4502C93653,,Val208(G608TG)PLeu(T608TG)Leu181(C527TT)PIeu(A527TT),4,P4502C9,P4502C9(2)2P4502C9n3132332000.8600.0800.0602000.7900.1250.0858600.8190.1070.0749980.7940.1060.1004360.97900.02111480.98900.01121960.97400.0262300.98300.0172040.95100.0491960.97400.0262000.9850.0100.0053000.97700.023,2P3P4502C931,1P331P3231P33,95%[5]Arg144PIle359Cys144PIle359Arg144PLeu359(P4502C931206ChinJClinPharmacolTher2004Jun;9(6)P4502C932P4502C933)0.790.9850.080.1250.0170.085,Arg144PIle359P4502C9Cys144,(0.01)Arg144PIle359,0.95,(3.1mgd-1)(6.1mgd-1)P4502C935(0.2%1.7%)(0%0.5%)3P4502C9P4502C9,,P4502C9,pHP4502C9,7,pKa3.88.1P4502C9,pKalogPP4502C9,[a,h][a]P4502C9,P4502C9,P4502C9,P4502C9(Ki0.10.2molL-1),P450P4502C9P4502C9,:(S2),()3.1,,,,,80%100%,cDNAP4502C9P4502C9[6]Lee(31P3131P3231P33),P4502C93131(AUC0),31P32,31P3331P311.51.9MinersP4502C93l32P4502C933680%KiKmP4502C9[7]P4502C9,[8],:,P4502C9,BrockmollerP4502C960%P4502C9,P4502C93.2,,,,P4502C9P4502C19,P4502C9,P4502C1910%42,52(4p2)52(HPPH),80%42P4502C9,,,42S2,P4502C912h30%[9]P4502C9HPPHHPPH3062004Jun;9(6),,HPPHS272P4502C93.3S2,,S2R235,P4502C9,,S285%P4502C96272(1Ø3)[10]S2R2R21S22,10%,P4502C96272,P4502C932P4502C933S25.527,,[11]P4502C933S272Vm,Km,VmPKm624,P4502C9S26272,,P4502C9S26272,,10,86%P4502C9(1.5mgd-1)38%,P4502C9[12]3.4(NSAIDS)P4502C9:P4502C9R2S242R2S22232,P4502C9S2O2P4502C942,(62)5232,3.52,,,,,80%,90%,P4502C9,P4502C9P4502C933,P4502C932[13]P4502C9:[14]P4502C92,(E23174)[15]4P4502C9P4502C9,P4502C9,P4502C9P4502C9,P4502C932,P4502C933[16]P4502C9,P4502C9(3)3P4502C9P4502C9S2406ChinJClinPharmacolTher2004Jun;9(6)()(4)4P4502C9P4502C9S2S2S2S2S2S2ZafirlukastS24.1P4502C915,P4501A2P4502B1P4502B2P4502C,P4502C9,,S2,()70%AUC[17],P4502C9S24501200mg,4.2,P4502C9(400mgd-1)3d,R2S233%47%S26272(200mgd-1)740%(5mgd-1)AUCHPPH[17]P4502C9,42S26272(100800mgd-1),S2AUC153%72%75%109%184%,P4502C96272,80%S2P4502C9,,,P4502C9P4503A410,P4502C9,1,2P4502C9,Ki10molL-1,S2,R2[18],,P4502C9P4502C95062004Jun;9(6),P4502C9,P4502C91LeeS,KimJM,ChungCS,ChoKJ,KimJH.PolymorphisminCYP2C9asanon2criticalfactorofwarfarindosageadjustmentinKoreanpatients[J].ArchPharmRes,2003;26(11):967-722SchwarzUI.ClinicalrelevanceofgeneticpolymorphismsinthehumanCYP2C9gene[J].EurJClinInvest,2003;33(2):23-303BozinaN,GranicP,LalicZ,TramisakI,LovricM,StavljenicRA.GeneticpolymorphismsofcytochromesP450:CYP2C9,CYP2C19,andCYP2D6inCroatianpopulation[J].CroatMedJ,2003;44(4):425-84YangJQ,MorinS,VerstuyftC,FanLA,ZhangY,XuCD,etal.FrequencyofcytochromeP4502C9allelicvariantsintheChineseandFrenchpopulations[J].FundamClinPharmacol,2003;17(3):373-65TakahashiH,WilkinsonGR,CaracoY,MuszkatM,KimRB,KashimaT,etal.PopulationdifferencesinS2warfarinme2tabolismbetweenCYP2C9genotype2matchedCaucasianandJap2anesepatients[J].ClinPharmacolTher,2003;73(3):253-636XieHG,PrasadHC,KimRB,andSteinCM.CYP2C9allelicvariants:ethnicdistributionandfunctionalsignificance[J].AdvDrugDelivRev,2002;54(10):1257-707InoueK,YamazakiH,ImiyaK,AkasakaS,GuengerichFP,ShimadaT.RelationshipbetweenCYP2C9and2C19genotypesandtolbutamidemethylhydroxylationandS2mephenytoin42hydroxylationactivitiesinliversofJapaneseandCaucasianPop2ulations[J].Pharmacogenetics,1997;7(2):103-1138KiddRS,StraughnAB,MeyerMC,BlaisdellJ,GoldsteinJA,DaltonJT.Pharmacokineticsofchlorpheniramine,phenytoin,glipizideandinanindividualhomozygousfortheCYP2C933allele[J].Pharmacogenetics,1999:9(1):71-809VanderWeideJ,SteijnsLS,vanWeeldenMJ,deHaanK.TheeffectofgeneticpolymorphismofcytochromeP450CYP2C9onphenytoindoserequirement[J].Pharmacogenetics,2001;11(4):287-9110ScordoMG,PengoV,SpinaE,DahlML,GusellaM,PadriniR.Influ