药理学课件第三章-药物代谢动力学

单击此处编辑母版标题样式,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,*,第二章药物代谢动力学,Pharmacokinetics,南开大学医学院,张京玲 韩姗,第二章药物代谢动力学 Pharmacokinetics南开,1,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目的,2,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。,Pharmacokinetics内容,3,Pharmacokinetics,Disposition of drug,(ADME system),Time-concentration relationship,Elimination kinetics,PharmacokineticsDisposition of,4,The End,The End,5,药理学课件第三章-药物代谢动力学,6,Disposition of drug,Drug transport,Absorption,Distribution,Metabolism or Biotransformation,Excretion,Disposition of drug Drug tra,7,Drug transport,Type,Feature,Influence factor,Con.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 Polarity,Ionization degree,a.,pH,b.,pKa,Drug transport TypeCon.gra,8,Feature,Feature,Passive transport,Active transport,Another name,Descending transport,Ascending transport,Concentration&electrochemical gradient,Obey,Against,Need special carrier,No,Yes,FeatureFeature Passive transpo,9,Feature,Feature,Passive transport,Active transport,Need energy,No,Yes,Saturable,No,Yes,Competitive inhibit,No,Yes,Types of distribution,Simple diffusion&filtration,Renal tubules,neuron,liver cells,Featured by,Most drugs,Few drugs,FeatureFeature Passive transpo,10,Influence factor,Effect,Molecular weight,Liposoluble property,Polarity,ionization,degree,(,PH&Pka,),Easy to transport,Small,High,Low,Non-dis-associated,Hard to transport,Large,Low,High,Dis-associated,Influence factorEffect Molecul,11,Handerson-Hasselbalch equation,Handerson-Hasselbalch equation,12,Absorption,Concept,Route,Speed,Degree,Influence factor,P.O(per os,or oral),First-pass elimination,I.V(intravenous),I.M(intramuscular,S.C(subcutaneou,P.r(per rectum),Inhalation;sublingual;,Lungstonguerectumimscposkin;,Lungstonguerectumimscposkin;,M.W.,Hydrophilic or lipophilic,pH,Blood flow,AbsorptionConceptP.O(per os,13,Distribution,Concept,Influence factor,Plasma protein binding,Feature,Result,Significance,Barrier,Blood-brain barrier(BBB),Placenta barrier,Blood-eye barrier,DistributionPlasma protein bi,14,Metabolism,Concept,Phase,Result,Enzyme,Enzyme induction,Phase,oxidations,reductions,hydrolysis；,Phase,conjugations,Special enzyme,Non-special enzyme,(hepatic microsomal mixed function oxidase system),Cytochrome P-450,NADPH,Flavoprotein,Inducers,Inhibitors,Activity or,Toxicity or,MetabolismConcept PhaseSpeci,15,Excretion,Concept,Route,Kidney,Filtration,Excretion,Bile,Hepatoenteral circulation,Milk,Saliva,Skin,Lungs,ExcretionConceptHepatoenteral,16,Time-concentration curve,time,Metabolism and elimination phase,C,max,Latent,period,Continuance,period,Remnant,period,MTC,MEC,T,max,Drug concentration(mg/L),Absorption and distribution phase,Time-concentration curve timeM,17,Time-concentration relationship,C,max,C,max,T,peak,Time-concentration relationshi,18,Elimination kinetics,Elimination kinetics,19,Elimination kinetics,Zero-order kinetics,Concept,Formula,C,t,=C,0,Kt;,0.5C,0,=C,0,Kt,1/2,figure,Feature,Significance,Elimination kineticsZero-order,20,Elimination kinetics,First-order kinetics,Concept,Formula,Figure,Feature,significance,Elimination kineticsFirst-orde,21,Elimination kinetics,Compartment model,One-compartment model,Two-compartment model,Three-compartment model,Elimination kineticsCompartmen,22,Elimination kinetics,Parameters,Bioavailability,(F),Absolute F,Relative F,Elimination kineticsParameters,23,AUC(P.O.）,AUC(I.V.）,Absolute F,=100%,Relative F,=100%,(AUC：Area under the curve),Biological Equivalent Trial,AUC(trial）,AUC(standard）,AUC(P.O.）Absolute F=,24,Elimination kinetics,Apparent volume of distribution,(Vd),Definition,Formula：,Clinical significance,Elimination kineticsApparent v,25,Elimination kinetics,Elimination rate constant,(Ke),Half-life,(t1/2),Concept,Formula,Clinical significance,Elimination kineticsEliminatio,26,药理学课件第三章-药物代谢动力学,27,Elimination kinetics,Area under curve,(AUC),formula,Clearance,(Cl),Definition,Formula,Clinical 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 kineticsArea under,28,Elimination kinetics,Steady state or Plateau,(Css),Cmax,Tpeak,Dose,Loading dose(D,1,),Maintenance dose(D,M,),P.O.,I.V.,Elimination kineticsSteady sta,29,练习,t,1/2,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？,30,药理学课件第三章-药物代谢动力学,31,药理学课件第三章-药物代谢动力学,32,药理学课件第三章-药物代谢动力学,33,药理学课件第三章-药物代谢动力学,34,药理学课件第三章-药物代谢动力学,35,药理学课件第三章-药物代谢动力学,3