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11(310009;1310031)::Cocktail::,Cocktail;;;TheadvancementinphenotypingstudyofdrugmetabolismZhouQuan(ZhouQ),YaoTongwei(YaoTW),ZengSu(ZengS)(TheSecondHospitalAffiliatedtoCollegeofMedicinalSciences,ZhejiangUniversity,Hangzhou310009)ABSTRACTOBJECTIVE:Topromotethephenotypingstudyinclinicalpractise.METHOD:Theprobedrugsofdrugmetabolismmethodsofphenotypeandrelatedfactorswerereviewed.TheCocktailstrategywasdescribedthemethodsofphenotypinggenotypingwascompared.RESULTS:Disease,coadministration,probedosage,sampletreatmentandcompliancearethemainfactorsaffectingphenotyping.CONCLUSION:Phenotypingwillhelpprovideasaferationalandeffectualprescription.Prosandconsexistinphenotypingaswellasingenotyping.TheCocktailstrategyhassepecialadvantages.Phenotypingstudyinspecialindividualsshouldbeenhanced.KEYWORDSmetabolism,polymorphism,phenotyping,genotyping(Geneticpolymorphism),,(Probedrug)(Phenotype),(Extensivemetabolizer,EM)(Poormetabolizer,PM),,,,11.1CYP1A2P45013%,40,CYP1A2CYP1A2()()(futamide)CYP1A213C1,72/CYP1A22005,5-7hr1,72/324200012176©1995-2005TsinghuaTongfangOpticalDiscCo.,Ltd.Allrightsreserved.CYP1A2,,[1]1.2CYP2A6P4504%,30-1002%,S2C421,72C82C72CYP2A6SM12502CYP2A6(S2),28PCR2RPLCCYP2A6189[2]1.3CYP2C9CYP2CP45018%,CYP2C9CYP2C9S2(),(42)CYP2C9,CYP1A12A62B62C192D6CYP2C9CYP2C1980%,CYP2C9[3]300mg12hrCYP2C9CYP2C931/14.16mgml-1(3.86-4.46),CYP2C931/25.52mgml-1(4.66-6.39),CYP2C931/35.65mgml-1(4.86-6.43)CYP2C931/152(2)252/(p2HPPH/P)0.43(0.39-0.47),CYP2C931/20.26(0.21-0.31),CYP2C932/20.14(0.13-0.14),CYP2C931/30.21(0.18-0.24),CYP2C933/30.02,p2HPPH/PCYP2C931/1p2HPPH/PCYP2C9[4]CYP2C933/3,S/R3.9:1,4-8mg/d,S/R0.500.251,S/RCYP2C933/3[5]1.4CYP2C19100,CYP2C195%,23%,(MP),,S2MP/R2MP,S/R=0.95,S/R0.95,S/R0.95[6]S2MP(S2MP/42OH2MP,HI),lgHI1.5,1.5[7]EMPM,PM,S/R,6100mg,(R)2pHPPH36hPMsEMs3.5,(S)2pHPPHPMsEMs1.3(R)2pHPPH20mg3hr(R)2pHPPHCYP2C19[8]100mg/,10[9]20mg3hr(/52),7[10]Tybring,(+)2CYP2C19,(-)2CYP3A4,CYP2C19(+)2/(+)252CYP2C19[11]1.5CYP2D6P4502.5%,1000,111,10mg100mg100mg20mg,18hr,/(MR),4MR,CYP2D6[12]DeZeeuw,(TLC)719,HPLC2TLC424200012176©1995-2005TsinghuaTongfangOpticalDiscCo.,Ltd.Allrightsreserved.,/0.32-5h6h,[13]100mg3hrlog[10MR](MR:/2)CYP2D68hr,S2AUCR35%,S/RCYP2D6Latini(150mg,tid),/52(MR1),,/52(MR2)[14]BotschHPLC8EMs15.4(5.6%,PMs42.2%51.6%CYP2D652,PMs52,PMsEMs,Botsch52/[15],CYP2D61.6CYP2E1P4507%,20(),,(42)N2()(CZX),90%CYP2E162(HCZX)CZX/HCZX(MR)250mg500mgCZX,2-4hMRCYP2E1[16]1.7NAT2(N2)N250%,25.6%,49.3%,25.1%,6h,52262232(AAMU)12(1X)12(1U),AAMU/(AAMU+1X+1U),/(MR),()2CocktailCocktail:,(),,,[17]Cocktail90%CYP2D6,10%CYP2C19CYP1A2CYP2D6,CYP2C19CYP1A2,CYP2C19CYP1A2[18]Cocktail,CocktailCYP2C19CYP2D6CYP2C19CYP2D6,,,CYP2C192D6NAT2[19]S2104NAT2CYP2D6CYP2C19CocktailN2S242,2[20]405(100mg250mg100mg524200012176©1995-2005TsinghuaTongfangOpticalDiscCo.,Ltd.Allrightsreserved.10mg100mg),8hr4-8hr,Cocktail5,CocktailCYP1A2CYP2E1NAT2CYP2D6CYP2C19[21]16140mg500mg,CocktailCYP2E1,CYP1A216%,20%,[22]33.1,HIV,NAT2,[23],II,[24]4730(+/52)12,3%CYP2C19,,CYP2C19[25]13CYP2D6,6EMsPMs,7PMsEMs4(2EMsPMs,2PMsEMs)CYP2D6[26]62CYP2E1,CYP2D6,CYP2D6[27]3.2CYP2D6,,,CYP2D6CYP2D6,,EMsPMs,EMsPMsPhenocopying,PMs,EMs,(CYP2D6),,(CYP2D6)53,110CYP2C19,20,3.3%[25]Cocktail,CYP2D6,CYP1A22C192E1NAT2[28]3.3250500mg,2-4h(/62)CYP2E1,750mg,62,62CYP2E1[16]3.4,S/RCYP2C19,[6]Basci2,,PMs3.7,EMs12.8/2.00,0.3[29],2[15]3.5,PMs,1032PMs,5PMs3PMs,4()624200012176©1995-2005TsinghuaTongfangOpticalDiscCo.,Ltd.Allrightsreserved.,,,,CYP2D6CYP2C19NAT2,CYP2D6[30]CYP2D6,AFMU/(AFMU+1X+1U)AFMU/1X[31],10030mg,3h,log[],PCR9(20mg,Bid),33,[32]5,CYP,,100%[33],,111,45,,[34]S/RCYP2C19,,S2MP,S/R,PMs,S/R,PMs,S/R,EM[6],CYP2D6,CYP2D6CYP2D6,MRCYP2D6,HPLC,,[35]50HIV26:24(:),1812,6,[23],1FuhrU,RostKL,EngelhardtR,etal.EvaluationofcaffeineasatestdrugforCYP1A2,NAT2andCYP2E1phenotypinginmanbyinvivoversusinvitrocorrelations.Pharmacogenetics,1996,6159.2NunoyaKI,YokoiT,KimuraK,etal.AnewCYP2A6genedeletionresponsiblefortheinvivopolymorphicmetabolismof(+)2cis23,52dimethyl222(32pyridyl)thiazolidin242onehydrochlorideinhumans.JPharmacolExpTher,1999,289(1)437.3TracyTS,MarraC,WrightonSA,etal.Studiesofflurbiprofen42hydroxylation.AdditionalevidencesuggestingthesoleinvolvementofcytochromeP4502C9.BiochemPharmacol,1996,52(8)1305.4SukruAynaciogluA,BrockmollerJ,BauerS,etal.FrequencyofcytochromeP450CYP2C9variantsinaTurkishpopulationandfunctionalrelevanceforphenytoin.BrJClinPharmacol,1999,48(3)409.5StewardDJ,HainingRL,HenneKR,etal.GeneticassociationbetweensensitivitytowarfarinandexpressionofCYP2C933.Pharmacogenetics,1997,7(5)361.6,,,.S242.,1999,34(5)338.724200012176©1995-2005TsinghuaTongfangOpticalDiscCo.,Ltd.Allrightsreserved.7,,,.S242.,1994,10(1)22.8IeiriI,MamiyaK,UraeA,etal.Stereoselective42hydroxylationofphenytoinrelationshipto(S)2mephenytoinpolymorphisminJapanese.BrJClinPharmacol,1997,43(4)441.9SomogyiAA,ReinhardHA,BochnerF.Pharmacokineticevaluationofproguanil:aprobephenotypingdrugforthemephenytoinhydroxylasepolymorphism.BrJClinPharmacol,1996,41(3)175.10HerrlinK,MasseleAY,JandeM,etal.BantuTanzanianshaveadecreasedcapacitytometabolizeomeprazoleandmephenytoininrelationtot