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ID:20288266
大小:1.26 MB
页数:70页
时间:2018-10-10
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1、PHAR751DietaryEffectsonMetabolismSarahBrown,Pharm.D.PharmacyPracticeResidentAsanteHealthSystemsbrown@asante.orgMetabolism:P-gpreviewSubstrate+Inhibitor=Substrate+Inducer=CYPMetabolismCytochromeP450Genesuperfamily:familiessubfamiliesenzymeOxidativemetabolism–PhaseILocationLiverSmallintestin
2、eMostabundantP450isCYP3A4Induction=Inhibition=Metabolism:CYPreviewSubstrate+Inhibitor=Substrate+Inducer=Metabolism&DietFoodMacronutrientsProteinCHOFatsMicronutrientsVitaminsMineralsIndolesDrinkGrapefruitjuiceOrangejuiceSevilleorangejuiceAlcoholDietcanalterenzymeactivityinfluencetheintensity
3、&durationofactionMacronutrients:ProteinIntake20%ofdietMalnutritioncontributestovariabilityindrugmetabolismCYP-mediatedInrats:CYP3Aactivity↓from18%to1%w/↓proteinintakeCYP1A2↓w/0.5%proteindietCYP1A1:nochangeProteinintake&theophyllinemetabolismCYP-mediated↓inClof30%whenreduceproteinintakefrom20%
4、to10%↓t½from8-9hto6hbyincreasingproteinfrom10%to40%.TPNpatientslowerplasmaClAnotherrouteofmetabolism:FMO1Flavin-containingmonooxygenase(FMO)1proteinOxidativemetabolismNon-inducibleInfluencedbydietaryintakeMicronutrient:IndoleeffectonmetabolismIndole-3-carbinol(I3C)Naturally-occurringchemical
5、foundincruciferousvegetablesInducesCYP1A1InhibitsFMO1AlsomarketedasdietarysupplementKatchamart,etal.Concurrentflavin-containingmonooxygenasedown-regulationandcytochromep-450inductionbydietaryindolesinrat:implicationsfordrug-druginteraction.DrugMetabolismandDisposition2000;28(8):930–936.Influe
6、nceofdietaryI3ConFMO1proteinlevelsKatchamart,etal.Concurrentflavin-containingmonooxygenasedown-regulationandcytochromep-450inductionbydietaryindolesinrat:implicationsfordrug-druginteraction.DrugMetabolismandDisposition2000;28(8):930–936.FMO(-)andCYP(+)Katchamart,etal.Concurrentflavin-containi
7、ngmonooxygenasedown-regulationandcytochromep-450inductionbydietaryindolesinrat:implicationsfordrug-druginteraction.DrugMetabolismandDisposition2000;28(8):930–936.Micronutrient:IndoleeffectonmetabolismoftamoxifenKatchamart,etal.Concurrentflavi
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