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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 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
2、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。,Pharmacokinetics,Disposition of drug ( ADME system )Time-concentration relationshipElimination kinetics,The End,Disposition of drug,Drug transport AbsorptionDistributionMetabolism or BiotransformationExcretion,Drug transport,TypeFeatu
3、reInfluence factor,Con. gradient;carrier; energy;saturable;competitive inhibit;,Molecular weight (M.W.)Liposoluble property or PolarityIonization degree a.pH b.pKa,Feature,Feature,Influence factor,Handerson-Hasselbalch equation,Absorption,ConceptRouteSpeedDegreeInfluence factor,P.O (per os, or oral)
4、 First-pass eliminationI.V (intravenous)I.M (intramuscularS.C (subcutaneouP.r ( per rectum)Inhalation; sublingual;,Lungstonguerectumimscposkin;,Lungstonguerectumimscposkin;,M.W.Hydrophilic or lipophilicpHBlood flow,Distribution,ConceptInfluence factor,Plasma protein bindingFeatureResultSignificanceB
5、arrierBlood-brain barrier (BBB)Placenta barrierBlood-eye barrier,Metabolism,ConceptPhase ResultEnzymeEnzyme induction, Phase oxidations, reductions, hydrolysis； Phase conjugations,Special enzymeNon-special enzyme(hepatic microsomal mixed function oxidase system)Cytochrome P-450NADPH Flavoprotein,Ind
6、ucersInhibitors,Activity or Toxicity or ,Excretion,ConceptRouteKidneyFiltration ExcretionBile,Hepatoenteral circulationMilkSalivaSkin Lungs,Time-concentration curve,time,Metabolism and elimination phase,Cmax,Latent period,Continuanceperiod,Remnantperiod,MTC,MEC,Tmax,Drug concentration(mg/L),Absorpti
7、on and distribution phase,Time-concentration relationship,Cmax,Cmax,Tpeak,Elimination kinetics,Elimination kinetics,Zero-order kineticsConceptFormula Ct = C0 Kt ; 0.5C0 = C0 Kt1/2,figureFeatureSignificance,Elimination kinetics,First-order kineticsConceptFormula,FigureFeaturesignificance,Elimination
8、kinetics,Compartment modelOne-compartment modelTwo-compartment modelThree-compartment model,Elimination kinetics,ParametersBioavailability, (F)Absolute FRelative F,AUC ( P.O.） AUC (I.V.）,Absolute F=100% Relative F = 100%,(AUC：Area under the curve),Biological Equivalent Trial,AUC ( trial） AUC (standa
9、rd）,Elimination kinetics,Apparent volume of distribution, (Vd)DefinitionFormula：Clinical significance,Elimination kinetics,Elimination rate constant, (Ke)Half-life, (t1/2)ConceptFormulaClinical significance,Elimination kinetics,Area under curve, (AUC)formulaClearance, (Cl) DefinitionFormulaClinical
10、significance,Cl 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 kidney.,Elimination kinetics,Steady state or Plateau, (Css)CmaxTpeakDose Loading dose (D1)Maintenance dose (DM),P.O.,I.V.,练习t1/2为8 h,按一级动力学消除的药物，95%被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9小时，该药的血浆半衰期是多少？,
