药理学课件南开大学第三章药物代谢动力学.pptVIP

第二章

药物代谢动力学Pharmacokinetics南开大学医学院张京玲韩姗Pharmacokinetics目的掌握药代动力学的基本概念及基本参数的计算。了解药代动力学的基本房室模型及血药浓度测定的临床意义。Pharmacokinetics内容一级动力学与零级动力学衰减原理。药物的跨膜转运机理与影响因素。药物吸收途径，第一关卡消除，肝肠循环，生物利用度，血浆蛋白结合原理与意义，药物分布不均匀性的原因与意义，表观分布容积，药物体内转化过程及代谢产物，肝脏微粒体药物代谢酶（肝药酶及P450）的特性，诱导与抑制，药物作用的消除即代谢，排泄与储存。药物消除速率常数与药物消除率的概念。药物排泄途径与机理，药物时效关系曲线，药物血浆半衰期，连续用药时药物在体内的蓄积，稳态血浓度与首剂速效剂量。药物血浆浓度监测的应用。01Dispositionofdrug(ADMEsystem)02Time-concentrationrelationship03EliminationkineticsPharmacokineticsTheEndMetabolismorBiotransformationAbsorptionDistributionExcretionDrugtransportDispositionofdrugDrugtransportTypeFeatureInfluencefactor①Con.gradient;②carrier;energy;③saturable;④competitiveinhibit;①FiltrationPassive②SimplediffusiontransportCarrier-mediatedtransportFacilitateddiffusionActivetransportComparison!①Molecularweight(M.W.)②LiposolublepropertyorPolarity③Ionizationdegreea.pHb.pKaFeatureFeaturePassivetransportActivetransportAnothernameDescendingtransportAscendingtransportConcentrationelectrochemicalgradientObeyAgainstNeedspecialcarrierNoYesFeatureFeaturePassivetransportActivetransportNeedenergyNoYesSaturableNoYesCompetitiveinhibitNoYesTypesofdistributionSimplediffusionfiltrationRenaltubules,neuron,livercellsFeaturedbyMostdrugsFewdrugsInfluencefactorEffectMolecularweightLiposolublepropertyPolarityionizationdegree(PHPka)EasytotransportSmallHighLowNon-dis-associatedHardtotransportLargeLowHighDis-associatedHanderson-HasselbalchequationAbsorptionConceptRouteSpeedDegreeInfluencefactor①P.O(peros,ororal)First-passelimination②I.V(intravenous)③I.M(intramuscular④S.C(subcutaneou⑤P.r(perrectum)⑥Inhalation;sublingual;Lungs＞tongue＞rectum＞im＞sc＞po＞skin;Lungs＞tongue＞rectum＞im＞sc＞po＞skin;M.W.HydrophilicorlipophilicpHBloodflowDistributionConceptInfluencefactor①PlasmaproteinbindingFea