3第三章 中药药动学幻灯片.pptVIP

第三章 中药药动学 Pharmacokinetics of Chinese herbal ingredient complex (PCHC) 胃肠道各部位的吸收面大小(m2) 口腔 0.5-l .0 直肠 0.02 胃 0.1-0.2 小肠 100 大肠 0.04-0.07 GI tract factors affecting absorption 一般规律 第一节 中药药动学研究现状 1963年大黄蒽醌衍生物的PK研究，带动中药有效成分经典药动学（C-T）的研究 20世纪80年代使用生物效应法（毒理效应法与药理效应法） 90年代提出中药复方PK，产生许多假设，如“证治动力学”、“辨证动力学”、“复方散弹”、“中药胃肠药动学”、“脾主药动学”等。 中药药效物质研究促进PK研究 药物代谢酶(CYP450)研究 细胞转运研究 化学-PD-PK三维体系 房室模型、Michaelis-Menten非线性模型等 代谢物组学（metabonome）：是反应机体状况的分子集合，所有对机体健康影响的因素均可反映在代谢物组中，基因、环境、营养、药物(外源物)和时间(年龄)最终通过代谢物组对表达施加影响 Difficult：How to fit all kind of lines into one line standing the herbal complex metabolic process in vivo without any consideration of metabolism degradation after the herb intake CBN injection Figure Time-concentration curves of puerarin (black one) and ginsenoside Rg1(red one) after CBN injection in rat Figure Time-relation between the plasma concentration of puerarin and ginsenoside Rg1 and inhibition rate of platelet aggregation ? Figure The relation between puerarin and ginsenoside Rg1 in plasma and the content of MDA in brain after CBN injection Figure Distribution and excretion of puerarin after iv injection of CBN (100 mg/kg) in rats Example 2 Capsule of YL2000, antifibrile herbal complex---Pharmacokinetics of baicarine, berberine and osthole, and pharmacodynemics of antifibrile effect in rat 黄芩苷与小檗碱的结果较相似，即黄芩苷和小檗碱在发热大鼠体内其吸收、消除、及达峰时间都较正常快，AUC(0-T)较正常小。蛇床子素在发热SD大鼠体内的消除、达峰时间都较正常慢，AUC(0-T)偏大 。 Kinetics of 3 ingredients and temperature in vivo 三成分药时浓度曲线与体温变化曲线 Coefficient of three ingredients and body temperation 通过相关性分析，提示我们黄芩苷可以作为解热作用的指示性成分（Marker）。其它二种成分与体温变化的相关性不明显。如果该复方以解热作为其药理作用的话，YL2000动力学可以按黄芩苷的药代动力学来描述。 * * Drug Administration Drug Concentration in Systemic Circulation Drug in Tissues of Distribution Drug Metabolism or Excreted Drug Concentration at Site of Action Pharmacologic Effect Clinical Response Toxicity Efficacy Pharmacokinetics Pharmacodynamics Absorption Distribution Elimination 简单扩散 载体转运 主动转运 易化扩散 Drug Transp