药理学课件南开大学第三章药物代谢动力学

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

2、。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,Disposition of drug ( ADME system ) Time-concentration relationship Elimination kinetics,The End,Disposition of drug,Drug transport Absorption Distribution Metabolism or Biotransformation Excretion,Drug transport,Ty

3、pe Feature Influence factor,Con. gradient; carrier; energy; saturable; competitive inhibit;,Molecular weight (M.W.) Liposoluble property or Polarity Ionization degree a.pH b.pKa,Feature,Feature,Influence factor,Handerson-Hasselbalch equation,Absorption,Concept Route Speed Degree Influence factor,P.O

4、 (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,Distribution,Concept Influence factor,Plasma protein bindin

5、g Feature Result Significance Barrier Blood-brain barrier (BBB) Placenta barrier Blood-eye barrier,Metabolism,Concept Phase Result Enzyme Enzyme induction, Phase oxidations, reductions, hydrolysis； Phase conjugations,Special enzyme Non-special enzyme (hepatic microsomal mixed function oxidase system

6、) Cytochrome P-450 NADPH Flavoprotein,Inducers Inhibitors,Activity or Toxicity or ,Excretion,Concept Route Kidney Filtration Excretion Bile,Hepatoenteral circulation Milk Saliva Skin Lungs,Time-concentration curve,time,Metabolism and elimination phase,Cmax,Latent period,Continuance period,Remnant pe

7、riod,MTC,MEC,Tmax,Drug concentration(mg/L),Absorption and distribution phase,Time-concentration relationship,Cmax,Cmax,Tpeak,Elimination kinetics,Elimination kinetics,Zero-order kinetics Concept Formula Ct = C0 Kt ; 0.5C0 = C0 Kt1/2,figure Feature Significance,Elimination kinetics,First-order kineti

8、cs Concept Formula,Figure Feature significance,Elimination kinetics,Compartment model One-compartment model Two-compartment model Three-compartment model,Elimination kinetics,Parameters Bioavailability, (F) Absolute F Relative F,AUC ( P.O.） AUC (I.V.）,Absolute F=100% Relative F = 100%,(AUC：Area unde

9、r the curve),Biological Equivalent Trial,AUC ( trial） AUC (standard）,Elimination kinetics,Apparent volume of distribution, (Vd) Definition Formula： Clinical significance,Elimination kinetics,Elimination rate constant, (Ke) Half-life, (t1/2) Concept Formula Clinical significance,Elimination kinetics,

10、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 kinetics,Steady state or Plateau, (Css) Cmax Tpeak Dose Loading