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1、PharmacokineticsChapter4Copyright(c)2004ElsevierInc.Allrightsreserved.PharmacokineticsFourbasicpharmacokineticprocessesareAbsorptionDistributionMetabolismExcretionCopyright(c)2004ElsevierInc.Allrightsreserved.FactorsAffectingDrugAbsorptionRateofdissolutionSurfaceareaBloodflowLipidsolubilitypHpar
2、titioningCopyright(c)2004ElsevierInc.Allrightsreserved.RoutesofAdministrationTwomajorgroupsEnteralViagastrointestinaltractParenteralOutsidethegastrointestinaltractUsuallyreferredtoas“byinjection”Commonroutes—intravenous,subcutaneous,intramuscularCopyright(c)2004ElsevierInc.Allrightsreserved.Drug
3、DistributionFactorsinfluencingdistributionareBloodflowtotissue–Exitingthevascularsystem–Theblood-brainbarrier–PlacentaldrugtransferCopyright(c)2004ElsevierInc.Allrightsreserved.DrugMetabolismBiotransformationEnzymaticalterationofdrugstructureLiver—primarysiteofdrugmetabolismP450system(cytochrome
4、P450)Copyright(c)2004ElsevierInc.Allrightsreserved.DrugMetabolism—ImplicationsTherapeuticconsequencesareAccelerateddrugexcretionDruginactivationIncreasedtherapeuticactionActivationofprodrugsToxicityvariationsCopyright(c)2004ElsevierInc.Allrightsreserved.SpecialConsiderationsinDrugMetabolismAgeIn
5、ductionofdrug-metabolizingenzymesFirst-passeffectNutritionalstatusCompetitionbetweendrugsCopyright(c)2004ElsevierInc.Allrightsreserved.DrugExcretionRemovalofdrugfromthebodyKidney—viathreeprocessesGlomerularfiltrationPassivetubularreabsorptionActivetubularsecretionCopyright(c)2004ElsevierInc.Allr
6、ightsreserved.TimeCourseofDrugResponsesPlasmadruglevelsMinimumeffectiveconcentration(MEC)ToxicconcentrationTherapeuticrangeDrughalf-lifeLoadingdoseMaintenancedoseCopyright(c)2004ElsevierInc.Allrightsreserved.DrugHalf-lifeThetimefortheamountofdruginthebodytodecreaseby50%Copyright(c)2004ElsevierIn
7、c.Allrightsreserved.
