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2LawFCP1,2(1.DepartmentofBiologicalSciences,SimonFraserUniversity,BurnabyBC,CanadaV5A1S6;2.,300070):199820002,:;;2;2:R969.1:A:100120971(2001)0120001205(PK),(c)(t),c2t;(PD)c(E),c2EPK2PD,(c2t),E2tPKPD,PD,PKPK2PD,10,PK2PD,,EmaxSEmax,PK2PD3,1PK2PD,,PK2PD,;;;;;;;()3,,,:20002102311.119931994,Jusko,PK2PD,4PK2PD/,PD7,/,2,mRNA,mRNA,mRNA,mRNA[1],PK2PD(ticlopidine),[2]100,200300mg(bid,8d),34d,,,,,Meibohm[3](budesonide)3mg800,16002400212,,,,120012281,PK2PD(mi2dazolam),,1.2Valle[4]PD(tra2madol)2(+)22(+)2o2DMT(-)2o2DMT,PD10min(+)2o2DMT2mgkg-1(10300min),2,2(2funaltrexamine)2mgkg-1,PK2PD2,3,7,822p2(TCDD)P45010mgkg-1(30min35d);(0.0130.0mgkg-1)1PD()CYP1A1/CYP1A2[5]1.3Marchand[6]PK2PD(nor2floxacin),,,(fenbufen)42(BPAA)BPAA,1hBPAA,BPAA,BPAA(6),(fantofarone),2(100300mg),PK2PD,,,[7]1.4PK2PD,2:Yang[8]PK2PD(QSAR)(),12,Lau[9]2(biologicallybaseddose2responsemodeling)2,2PK2PD,,,PK2PD,2.1,,,Rousseau[10]PK2PD,BayesPK2PD,,Czock[11]PK2PD,2,Beringer[12]PK2PD(tobramycin)10mgkg-1d-1,q24h,q12hq8h3,q24h/MICTMIC,PK2PD,()2ForeignMedicalSciencesSectiononPharmacy2001Feb;28(1)2.2Olsson2Gisleskog[13]PK2PD52(DHT)(finasteride)(dutasteride)52,28dPD,88%116%;Johansson[14]PK2PD(PEP)240320mgPEP41,500pmolL-1,50%Thomas[15]024hAUCMIC100,;,,1003,,,2,2:(1),;(2),,b,PK2PD,,[16]HoffmanLaRoche18PK2PD:,,,PD[17]PK2PD/,3.1PK2PD,,3(valpromide),1213,2[18],3.2,,,,,,,,,,,,,,,,;;;,,22,PK2PD,,,PK2PD:WinNonlin(Pharsight,MountainView,CA,USA)ADAPT(BiomedicalSimulationsResource,LosAnge2les,CA,USA):NONMENNPML30,PK2PD105,9,320012281[19],(mycopheno2latemofetil)[20],FDA3.3,,PK2PD0.06h-1[21]Singh[22]PK2PDFDA,PK2PD2,()4PK2PD:2PK2PD,,PD,E2c,,,,E2c:,,(efficacy)PK2PD,,,,,,PK2PDPK2PD,,:,,,,PK2PD,,[1]SunYN,DuBoisDC,AlmonRR,etal.Dose2dependenceandrepeated2dosestudiesforreceptor/gene2mediatedphar2macodynamicofmethylprednisoloneonglucocorticoidrecep2tordown2regulationandtyrosineaminotransferaseinductioninratliver[J].JPharmacokinetBiopharm,1998,26(6):619-648.[2]KatashimaM,YamadaY,YamamotoK,etal.Analysisofantiplateleteffectofticlopidineinhumans:modelingbasedonirreversibleinhibitionofplateletprecursorsinbonemar2row[J].JPharmacokinetBiopharm,1999,27(3):283-296.[3]MeibohmB,DerendorfH,MollmannH,etal.Mecha2nism2basedPK/PDmodelforthelymphocytopeniainducedbyendogenousandexogenouscorticosteroids[J].JClinPharmacolTher,1999,37(8):367-376.[4]ValleM,GarridoMJ,PavonJM,etal.Pharmacokinetic2pharmacodynamicmodelingoftheantinociceptiveeffectsofmainactivemetabolitesoftramadol,(+)2o2desmethyltra2madoland(-)2o2desmethyltramadol,inrats[J].JPhar2macolExpTher,2000,293(2):646-653.[5]SantostefanoMJ,WangX,RichardsonVM,etal.ApharmacodynamicanalysisofTCDD2inducedcytochromeP450geneexpressioninmultipletissues:dose2andtime2dependenteffects[J].ToxicolApplPharmacol,1998,151(2):294-310.[6]MarchandS,PariatC,BouquetS,etal.Pharmacokinetic2pharmacodynamicmodellingoftheconvulsantinteractionbe2tweennorfloxacinandbiphenylaceticacidinrats[J].BrJPharmacol,2000,129(8):1609-1616.[7]BellissantE,GiudicelliJF.Pharmacokinetic2pharmaco2dynamicmodelforfantofaronecardiacandbrachialhaemo2dynamiceffectsinhealthyvolunteers[J].BrJClinPhar2macol,1999,48(6):801-810.[8]YangRS,ThomasRS,GustafsonDL,etal.ApproachestodevelopingalternativeandpredictivetoxicologybasedonPBPK/PDandQSARmodeling[J].EnvironHealthPerspect,1998,106(Suppl6):1385-1393.[9]LauC,AndersenME,Crawford2BrownDJ,etal.Evalua2tionofbiologicallybaseddose2responsemodelingfordevel2opmentaltoxicity:aworkshopreport[J].RegulToxicolPharmacol,2000,31(2Pt1):190-199.4ForeignMedicalSciencesSectiononPharmacy2001Feb;28(1)[10]RousseauA,MarquetP,DebordJ,etal.Adaptivecontrolmethodsforthedoseindividualisationofanticanceragents[J].ClinPharmacokinet,2000,38(4):315-353.[11]CzockD,GiehlM,KellerF.Aconceptforpharmacokinet2ic2pharmacodynamicdosageadjustmentinrenalimpairment:thecaseofaminoglycosides[J].ClinPharmacokinet,2000,38(4):367-375.[12]BeringerPM,VinksAA,JelliffeRW,etal.Pharmacoki2neticsoftobramycininadultswithcysticfibrosis:implica2tionsforonce2dailyadministration[J].AntimicrobAgentsChemother,2000,44(4):809-813.[13]Olsson2GisleskogP,HermannD,Hammarlund2UdenaesM,etal.Validationofapopulationpharmacokinetic/pharma2codynamicmodelfor5alphareductaseinhibitors[J].EurJPharmSci,1999,9(4):291-299.[14]JohanssonCJ,GunnarssonPO.Pharmacodynamicmodeloftestosteronesuppressionafterintramusculardepotestrogentherapyinprostatecancer[J].Prostate,2000,44(1):26-30.[15]ThomasJK,ForrestA,BhavnaniSM,etal.Pharmacody2namicevaluationoffactorsassociatedwiththedevelopmentofbacterialresistanceinacutelyillpatientsduringtherapy[J].AntimicrobAgentsChemother,1998,42(3):521-527.[16]SheinerLB,SteimerJL.Pharmacokinetic2pharmacodynamicmodelingindrugdevelopment[J].AnnuRevPharmacolToxicol,2000,40:67-95.[17]ReignerBG,WilliamsPE,PatelIH,etal.Anevaluationoftheintegrationofpharmacokineticandpharmacodynamicprinciplesinclinicaldrugdevelopment.ExperiencewithinHoffmannLaRoche[J].ClinPharmacokinet,1997,33(2):142-152.[18]SussanS,DaganA,BialerM.Pharmacokineticanalysisandanticonvulsantactivityofglycineandglycinamidederivatives[J].EpilepsyRes,1999,33(1):11-21.[1
本文标题:药代动力学药效学结合模型的应用进展-药代动力学2药效学结
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