课件：药物代谢动力学.ppt

第二章 药物代谢动力学 Pharmacokinetics,Across membrane and lipid,Across aqueous channel,Carrier-mediated transport,Outside,Inside,Manners of Transport Across Membrance,Passive transport,Routes of Drug Administration,Enteral within or by way of the GI tract Oral (PO), rectal, sublingual Parenteral Not within the alimentary canal Inhalation, IM, SC, IP, topical Central Into the brain or spinal cord Intrathecal,Routes of Drug Administration common abbreviations,PO = per os = oral IV = intravenous = into the vein IM = intramuscular = into the muscle SC = subcutaneous = between the skin and muscle IP = intraperitoneal = within the peritoneal cavity icv = intracerebroventricular = directly into the ventricle of the brain,Factors Affecting Response to Drugs Dosage Route of Administration Rate of Absorption Rate of Elimination Physiochemical properties of the drug age, sex, species, metabolism, etc,血 浆 阿 司 匹 林 浓 度 (mg/L),时间（min）,口服和静脉注射阿司匹林659mg后的时-量曲线,三种不同的生物利用度 A.吸收速度快、吸收量完全 B.吸收速度与A相同，但吸收量仅为A的50% C.吸收量完全，但吸收速度为A的50%,时间（h）,Elimination kinetics 1. First-order elimination kinetics,2019/9/1,13,可编辑,三种不同给药方案对稳态浓度的影响 A. 缩短给药时间 B. 增加给药剂量 C. 负荷量给药,2. Zero-order elimination kinetics,Pharmacokinetic Evaluation of Gepirone Immediate-Release Capsules and Gepirone Extended-Release Tablets in Healthy Volunteers,JOURNAL OF PHARMACEUTICAL SCIENCES, VOL. 92, NO. 9, SEPTEMBER 2003,Gepirone is a 5-HT1A agonist for the treatment of major depression. half-life of 3 h and good oral bioavailability, and undergoes extensive first-pass metabolism,Because of its rapid absorption and short half-life, the gepirone-IR (immediate-release formulation) must be administered at least twice daily. This regimen results in high peak concentrations and marked peak-to-trough fluctuations in plasma concentrations.,These fluctuations may contribute to an increased incidence of adverse events, such as nausea, dizziness, headache, and somnolence, and have the potential to result in lower patient compliance and reduced effectiveness. extended-release gepirone formulation(ER) immediate-release formulation(IR),Figure 1. Mean gepirone plasma concentrations following administration of gepirone-IR formulations (10mgq12 h,n=12) or gepirone-ER formulations (ER-1: 20 mg q24 h, n=12; ER-2: 20 mg q24 h, n=12; ER-3: 25 mg q24 h, n=12).,Figure 2. Mean 1-PP plasma concentrations following administration of gepirone-IR formulations (10 mg q12 h, n