体外代谢清除率模型用于药物肝代谢过程的研究-黄峰.ppt

《体外代谢清除率模型用于药物肝代谢过程的研究-黄峰.ppt》由会员上传分享，免费在线阅读，更多相关内容在PPT专区-天天文库。

1、Major:chinesetraditionalmedicineName:黄峰（2110948107）InvitromethodstopredictmetabolicclearancerateofDrugshepaticmetabolismContentsPreclinicalpredictiontheoryMathematicalModeAccuracystudyTheproblemtobesolved90%ofmedicinesaremainlyinvolvedinthebiologicalco

2、nversionof——P450.Theliveristhemainorganofdrugmetabolism.Invitromodelhasbeensuccessfullyusedtopredictinvivostudiesoflivermetabolism.PreclinicalpredictiontheoryTheoreticalbasisPremise:baseinthehepaticmetabolismThefirststep:Parametersobtainedinvitro—intri

3、nsicclearanc=ClintTheseceondstep:usingSFchangetheClintandthenusingthemodelandthisresulttoPredictinvivoclearance.IwatsuboT,HirotaN,OoieT,etal.Pctionofinvivodrugmetabolisminthehumanliverfrominredivitrometabolismdata.[J].PharmacolTher,1997,73(2):147.About

4、CLintMichaelis-mentenequationCdrug《KmRemember：Clearallthemetabolites(1—1)CLint=Vmax/KmCLint=V0/SWhenMetabolitesisnotclearGeneralProcess——AnothermethodDrughalf-life=T1/2(1—2)CLint=0.693V/T1/2Relevantconversionfactors—Scalingfactors(SF)SFisaconversionfac

5、tor.SFisusedtotranslantClinttotheliverclearanceg:Inthelivermicrosomesexperiment,SF‘svalueisoftenusedcontaining45mgmicrosomalproteinpergramofliver(Ratsandhuman).MathematicalmodelTherearethreemodelsusingtopredictinvivoclearance:Well-stirredmodelParallelt

6、ubemodelDispersionmodelThesemodelscanusetheClinttocalculatetheliverclearanceMathematicalmodelWell-stirredmodelOrvenousequilibriummodelFreedrugconcentrationinbloodvesselsisequaltothedrugconcentrationinlivercells.MathematicalmodelParalleltubemodelConcent

7、rationdecreasedMathematicalmodelDispersionmodelMorecomplicatedformula,butclosertophysiologicalconditionsThesethreemodelsfitforDrugswithlowclearance.thedrug‘swaytometabolizeComparisonofthreemodelsDispersionmodelcangiveabetterfittingresultsHowtochooseAcc

8、uracystudy——ⅠTheimpactofproteinbindingObachetal.Comparisonof14kindsofcompoundsinvivo,invitroclearanceShibataetal.Designedanewwaytoignorethedrugandproteinandtissuebinding(1—3)Average-folderror=10(log(practictal/actual))/nAccuracystudy——Ⅱ