数学模型在药效动力学研究中的应用3ξ

[J].,1997,23(12):8362838.[23],,,.[J].,1993,9(4):1922194.[24]FuchuHe,ChutseWu,QiangTu,etal.Humanhepaticstimulatorsubstance:aproductofgeneexpressionofhu2manfetallivertissue[J].Hepatology,1993,17(2):2252229.[25],,,.[J].,1994,10(2):1652168.[26],,,.[J].,1995,17(2):1022104.[27],.[J].,1993,12(3):1402141.[28],,.18[J].,1999,18(2):95.3X1,2,2(1.,200003;2.,210009)::;;:O141.4;R969.1:A:1001-5094(2000)02-0077-05TheApplicationofMathematicalModelsintheStudyofPharmacokinetic2dynamicsLIUGao2lin1,ZHANGZheng2xing2,AnDeng2qui2(1.DepartmentofClinicalPharmacology,ChangzhengHospital,theSecondMilitaryMedicalUniversity,Shanghai200003,China;2.ChinaPharmaceuticalUniversity,Nanjing210009,China)Abstract:Thecomprehensivestudyandreasoningontherelationofpharmacodynamicsandpharma2cokineticsaredevelopingorientationsofhospital2pharmacy.Theapplicationofmathematicalmodelsinthestudyofpharmacokinetic2dynamicsweresurveyed.Keywords:Pharmacodynamics;Pharmacokinetics;Mathematicalmodel(pharmacodynamics)(pharmacokinetics),,,:,;;,,222,,,77X:1999206201;:2000201218©1994-2007ChinaAcademicJournalElectronicPublishingHouse.Allrightsreserved.[1][2],2(Bevan2tolol)[3],[4],Benzodiazepine[5],H22[6,7][8]11.1(linearmodel)E=SC+E0(1)(1)E,S,CE0,C=0,(baselineeffect),,,,1.2(log2linearmodel)E=SlogC+I(2)(2)I,,20%280%[9],,E,Hill,,1.3Emax(Emaxmodel)E=EmaxC/(EC50+C)(3)Hill,,2,Emax,EC5050%EmaxEmax,,,,(3),:lg[E/(Emax-E)]=lgC-lgEC50(4)lg[E/(Emax-E)]lgC,Hill(4)1,lg[EC50E],C[10],E,,1.4Emax(InhibitingEmaxmodel)E=E0-EmaxE/[IC50+C](5),E0,IC5050%,Emax,1.5SEmax(SigmoidEmaxmodel)E=EmaxCS/[(EC50)S+CS](6)(6)HillWagner,S,,S=1,Emax;S1,(6)S,,;S1,,SEmax2,,,;S,(6),:lg[E/(Emax-E)]=SlgC-SlgEC50(7)Hill,EC50S222.1,[11][12][13],:;;2.2,,:,872000242©1994-2007ChinaAcademicJournalElectronicPublishingHouse.Allrightsreserved.(lagtime),;(),,,2,(counterlockwisehysteresis),(1),,(clockwisehysteresis),()12,Wagner(LDS)(mentalperfor2mances),,:,,;,,,,,Reidenerg,,,2.3Sheiner[4][12],,(effectdepartment)(2),,KeoCss502SX1Xe;K1eKeo,K1e,,,Keo,Keo,,,KeoXe:dXe/dt=K1eX1-KeoXe(8)X0,,X1=X0e2Kt,(8),Xe=K1eX0(e2Kt-e2Keot)/(Keo-K)(9),Sheiner,,dXe/dt=0,(8)K1eX1=KeoXe,X1=KeoXe/K1e,V1,Css=KeoXe/K1eV1,Hill(6),:E=Emax(KeoX1/K1eV1)S/[(ECss50)S+(KeoXe/K1eV1)S](10)Colburn[14],,,,,EmaxSEC50,2,:C=X0(K21-)e2t/Vc(-)+X0(K21-)e2t/Vc(-)(11)97©1994-2007ChinaAcademicJournalElectronicPublishingHouse.Allrightsreserved.=K1eX0(K21-)e2t/Vc(-)(Ke0-)+K1eX0(K21-)e2t/Vc(-)(Keo-)+K1eX0(K21-Keo)e2Keot/Vc(-Keo)(-Keo)(12)2,CeHill,22,,22,Hill3,,,;(),,:,;,,,;,2;,,(EEG);pH;2,,,,,,Hill,,:[1]KuhlmannJ,DohrmannM,MarcinS.Effectsofquinidineonpharmacokineticsandpharmacodynamicsofdigitoxinachievingsteady2stateconditions[J].ClinPharmacolTher,1986,39:2882294.[2],.[J].,1991,12:7211.[3]LiuXQ,YeXL,ZhuHQ,etal.Plasmabevantololconcen2trationandheartrateinrabbits[J].ActaPharmacolSini2ca,1993,14:2002202.[4]KleinbloesemCH,vanBrummelenP,vandeLindeJA,etal.Nefedipinekineticsanddynamicsinhealthysubjcets[J].ClinPharmacolTher,1984,35:7422749.[5]KrobothPD,SmithRB,StoehrGP,etal.Pharmacody2namicevaluationofthebenzodiazepineoralcontracepticin2teraction[J].ClinPharmacolTher,1985,38:5252532.[6],,,.[J].,1991,12:3362340.[7],,,.[J].,1993,14:2572259.[8],.[J].,1994,10:87292.[9]LevyG.Kineticsofpharmacologiceffects[J].ClinPhar2082000242©1994-2007ChinaAcademicJournalElectronicPublishingHouse.Allrightsreserved.:3622372.[10]HolfordNHG,SheinerLB.Kineticsofpharmacologicalresponse[J].PharmacolTher,1982,16:1432146.[11]FeelyJ,SterensonIH,CrooksJ.Propranololdynamicsinthyrotoxicosis[J].ClinPharmacolTher,1980,28:40244.[12]PancorboS,BubrickMP,ChinTWF,etal.Cimetidinedynamicsaftersingleintravenousdoses[J].ClinPharma2colTher,1982,31:83288.[13]SeidemanP,GrahnenA,HaglundK,etal.Prazosindy2namicsinhypertension:relationshiptoplasmaconcentra2tion[J].ClinPharmacolTher,1981,30:4472454.[14]ColburnWA.Simultaneouspharmacokineticandpharma2codynamicmodeling[J].JPharmacokinetBiopharm,1981,9:3672388.3X1,2,3(1.,253500;2.;3.,250031):FDA,:;;22,8;:R512.32;R186:A:1001-5094(2000)02-0081-04BreakthroughintheDevelopmentofGroupBMeningitisVaccineZHANGCui2ling1,GUOZhong2wu2,YUANCheng3(1.LingxianHospitalofShandongProvince,Lingxian253500,China;2.NationalResearchCouncilofCanada,Canada;3.DepartmentofPharmacology,GeneralHospitalofJinanMititaryRegion,Jinan250031,China)Abstract:TheFoodandDrugAdministration(FDA)ofAmericarecentlyapprovedtheclinicaltrialofaglycoconjugateGroupBmeningitis(GBM)vaccinebasedonthechemicallymodifiedGBMcapsularpolysaccharied.Theprocessofdevelopment,themechanismofactionandtheimmunologicalproper2tiesofthenovelglycoconjugatevaccine,whichisfirstsuccessfulGMBvaccineandofaguidingsignifi2cancetodevelopmentofothervaccines,werebrieflyintroduced.Keywords:GroupBmeningitisvaccine;Glycoconjugate;22,82Polysialicacid;Chemicalmodification[1],70%,,,,WHO,(),(NationalResearchCouncilofCana2da)JenningsHJ,FDA,,PasteurMerieuxConnaughtCompanyNorthAmericaVaccineCompany,,,,W2135Y18X:1999204207;:2000201227©1994-2007ChinaAcademicJourn