基础医学课件-药动学.pptVIP

2.2 First order kinetics 一级动力学 n ＝ 1 dC / dt ＝ －KC Ct ＝ C0e－Kt lnCt ＝ lnC0－Kt Kt＝lnC0－lnCt＝ln(C0 / Ct) when Ct＝1/2C0，t＝t1/2， then t1/2＝ln2/K＝0.693/K Part B Kinetic Processes First order kinetics 一级动力学 A. eliminated at same rate per unit time 单位时间内按相同比例消除 B. t1/2 is a constant 半衰期是常数 C. logC-T curve is linear logC-T曲线为直线 D. steady state (Css) after 4-5 t1/2 反复给药后经4~5个t1/2达到稳态 Part B Kinetic Processes Kinetic properties of C-T curves after single bolus injection of drug (1) Binding of drug to plasma proteins 药物与血浆蛋白结合 Bound drug: can not distribute / inactive temporally 不能分布/暂时失活 reversible (storage form)/ percentage of binding可逆/结合百分率 plasma protein capacity 血浆蛋白量 competitive displacement 竞争性置换 Part A Pharmacokinetic Processes Competitive displacement 竞争性置换 Class I drugs: Dose less than available binding sites 剂量小于结合位点. Most drug molecules are bound to the proteins and free drug concentration is low. Class II drugs: Dose greater than available binding sites 剂量大于结合位点. Most proteins contain a bound drug and free drug concentration is significant. Class I + Class II drugs: Displacement of Class I drug occurs when a Class II drug is administered simultaneously. Part A Pharmacokinetic Processes competitive displacement Example: Class I: Tolbutamide (甲苯磺丁脲) Class II: Sulfonamide (磺胺类药物) (2) Physic-chemical properties of the drug 药物的理化特性 (3) Blood flow and re-distribution 血流和再分布 (4) Affinity to organs or tissues 组织或器官的亲和力 (5) Barriers 屏障 Blood-brain barrier (BBB) 血脑屏障 Placental barrier 胎盘屏障 Blood-eye barrier 血眼屏障 Part A Pharmacokinetic Processes Blood-brain barrier (BBB) Able to pass through Unable to pass through Small molecules 小分子 Large molecules Lipid-soluble 脂溶性 Water-soluble Transporter-mediation 转运体介导 Amount of drug passing through blood-brain barrier Percentage of drug in c.s.f. Increases when