药理学课件南开大学第三章药物代谢动力学.ppt

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1、第二章药物代谢动力学 Pharmacokinetics南开大学医学院张京玲 韩姗Pharmacokinetics目的目的 掌握药代动力学的基本概念及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力学的基本房室模型及血药浓度测定的临床意义。度测定的临床意义。Pharmacokinetics内容内容一级动力学与零级动力学衰减原理。药物的跨膜转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运机理与影响因素。药物吸收途径，。药物吸收途径，第一关卡消除，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肝肠循环，生物利用度，

2、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，药物体内转化过程及代谢产物，肝脏微粒体药物代肝脏微粒体药物代谢酶（肝药酶及谢酶（肝药酶及P450）的特性，诱导与抑制，）的特性，诱导与抑制，药物药物作用的消除即代谢，排泄与储存。药物消除速率常作用的消除即代谢，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，物时效关系曲线，药物血浆半衰期药物血浆半衰期，连续用药时药，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。药物在

3、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。物血浆浓度监测的应用。Pharmacokinetics1.Disposition of drug(ADME system)2.Time-concentration relationship3.Elimination kineticsDisposition of drug 1.Drug transport 2.Absorption3.Distribution4.Metabolism or Biotransformation5.Excretion Drug transport 1.Type2.Feature3.Influence fac

4、torCon.gradient;carrier;energy;saturable;competitive inhibit;Filtration Passive Simple diffusion transport Carrier-mediated transport Facilitated diffusion Active transport Comparison!Molecular weight(M.W.)Liposoluble property or PolarityIonization degree a.pH b.pKaHanderson-Hasselbalch equationAbso

5、rption1.Concept2.Route3.Speed4.Degree5.Influence factorP.O(per os,or oral)First-pass eliminationI.V(intravenous)I.M(intramuscularS.C(subcutaneouP.r(per rectum)Inhalation;sublingual;Lungstonguerectumimscposkin;Lungstonguerectumimscposkin;M.W.Hydrophilic or lipophilicpHBlood flowDistribution1.Concept2

6、.Influence factorPlasma protein bindingFeatureResultSignificanceBarrierBlood-brain barrier(BBB)Placenta barrierBlood-eye barrierMetabolism1.Concept2.Phase 3.Result4.Enzyme5.Enzyme induction Phase oxidations,reductions,hydrolysis；Phase conjugations Special enzymeNon-special enzyme(hepatic microsomal

7、mixed function oxidase system)Cytochrome P-450NADPH FlavoproteinInducersInhibitorsActivity or Toxicity or ExcretionConceptRouteKidneylFiltration lExcretionBileHepatoenteral circulationMilkSalivaSkin Lungs Time-concentration curve timeMetabolism and elimination phaseCmaxLatent periodContinuanceperiod

8、RemnantperiodMTCMECTmaxDrug Drug concentration(mg/L)concentration(mg/L)Absorption and distribution phaseTime-concentration relationshipCmaxCmaxTpeakElimination kineticsElimination kinetics1.Zero-order kineticsConceptFormula Ct=C0 Kt;0.5C0=C0 Kt1/2figureFeatureSignificanceElimination kinetics2.First-

9、order kineticsConceptFormulaFigureFeaturesignificanceElimination kinetics3.Compartment modelOne-compartment modelTwo-compartment modelThree-compartment modelElimination kinetics4.ParametersBioavailability,(F)lAbsolute FlRelative F AUC(P.O.）AUC(I.V.）Absolute F=100%Relative F=100%(AUC：Area under the c

10、urve)Biological Equivalent Trial AUC(trial）AUC(standard）Elimination kineticsApparent volume of distribution,(Vd)lDefinitionlFormula：lClinical significanceElimination kineticsElimination rate constant,(Ke)Half-life,(t1/2)lConceptlFormulalClinical significanceElimination kineticsArea under curve,(AUC)

11、lformulaClearance,(Cl)lDefinitionlFormulalClinical significanceCl means the total rate of the elimination of the drugs by the liver and the kidney.It doesnt equal to the elimination speed of the drugs(RE).It has nothing to do with the dose of drugs(A),but is influenced by the state of the liver and

12、kidney.Elimination kineticsSteady state or Plateau,(Css)CmaxTpeak5.Dose Loading dose(D1)Maintenance dose(DM)P.O.I.V.练习练习1.t1/2为为8 h,按一级动力学消除的药物，按一级动力学消除的药物，95%被被排出体外需多长时间排出体外需多长时间?2.某药在体内按一级动力学消除，在其吸收达某药在体内按一级动力学消除，在其吸收达高峰后两次抽血，其血药浓度分别为高峰后两次抽血，其血药浓度分别为180 ug/ml、22.5 ug/ml，两次抽血间隔两次抽血间隔9小时，小时，该药的血浆半衰期是多少？该药的血浆半衰期是多少？