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ID:49129015
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时间:2020-01-31
《酸枣仁油软胶囊的新药开发研究.ppt》由会员上传分享,免费在线阅读,更多相关内容在教育资源-天天文库。
1、CHAPTER3Pharmacokinetics(bodyactsondrug)PHARMACOLOGICPRINCIPLES(sitesofaction)bindingfree(accumulation)freebindingdrugsposcim(plasma)Freedrugsbindingdrugsmetabolites(renal)excretionMetabolism(liver)absorptiondistributiondistributiondistributionpharma
2、cokineticsUndergoingofdrugsinbodytransformationoutofbodytransportperoralsubcutaneousintramuscularThemembraneswithporearecomposedoflipidsandproteinsinaratioof70:1.Theliquid-formdouble-deckofmembranesisformedfromlipidmolecules;Thespecialproteinsinserte
3、dintothedouble-deckarereceptors,enzymes,ionchannels,carriers……Ⅰ.Drugpermeationacrossmembranes1.membranepharmacokineticspermeationacrossmembranesfenestratedmembraneHighconcentrationLowoncentrationATPmembraneecto-Intra-lipiddiffusionporefiltrationcarri
4、erFacilitatedtransportActivetransportAdrugmoleculemovesfromasideofmembranerelativelyhighconcentrationtoanothersideoflowconcentrationwithoutrequiringenergy,untilanequilibriumhasbeenachievedonbothsidesofthemembrane.2.Passivetransportacrossmembranes(dow
5、nhill)highlowequilibriumpharmacokineticsLipiddiffusion;Filtration;Facilitatedtransportpermeationacrossmembranes…..…..…..…..…..…..…..…..…..…..…..…..…..…....…..…..…..…....NonionizedformIonizedform1)Lipiddiffusion(Simplediffusion)iontrappinglesspolarmo
6、leculespolarmoleculesThemostimportantmechanismofdrugtransportpharmacokineticspH(pKa)┐pKaispHwhenIonizedrateis50%permeationacrossmembranesmorelipidsolublelesslipidsolubleeasypermeationhardpermeationDrugmovementacrossmembranesisdrivenbyaconcentrationgr
7、adientaftersolutioninthelipidsofmembranes.k1k2k1[H+][A-]k1[H+][B]Ka=──=─────Ka=──=────k2[HA]k2[BH+][A][B]pKa=pH-log───pKa=pH-log───[HA][BH+][A-][B]pH-pKa=log───pH-pKa=log───[HA][BH+]HA(weakacids)B(weakbases)k1k1HAH++A-B+H+BH+k2k2pharmacokineticsL
8、ipiddiffusion[A-][B]───=10pH-pKa───=10pH-pKa[HA][BH+]weakacidsweakbases★pH↑↓→[A-]↑↓★pH↑↓→[BH+]↓↑→ionization↑↓→ionization↓↑→lipidsolution↓↑→lipidsolution↑↓→permeation↓↑→permeation↑↓pharmacokinetics[A-][B]───=10pH-pKa───=10pH-pKa[HA][BH+]Lipiddiffusio
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