Chpt 03 Pharmacokinetics中药代学.pptVIP

Chapter 3 Pharmacokinetics药物代谢动力学 Regardless of the route of administration, a drug almost always must cross a biological membrane(s) to reach its site of action. Absorption, distribution and elimination of a drug also all involve its passage across cell membranes. I. Drug transport across membranes 1) GI epithelial cells 2) Vascular endothelium 3) Blood brain barrier 4) Subcellular membranes; nucleus, vesicle Cell membrane Fluid mosaic model-membrane is fluid Bimolecular lipid sheet with polar groups outside and non-polar groups inside Nonpolar molecules (uncharged drugs )-lipid soluble passes through lipid portion Polar molecules-water soluble pass through specific pores only Drugs are organic compounds ---only a portion dissociate into ions The rate of diffusion of uncharged drugs is determined primarily by lipid solubility What we have to know is how much is in undissociated (non-ionized) and dissociated（ionized）forms for a drug because in diffusion drugs cross in non-ionized form ionized-drug will not pass through the membrane 被动转运的特点 ①不需要载体； ②不消耗能量（ATP）； ③无饱和现象； ④不同药物同时转运时无竞争性抑制现象； ⑤当可跨膜转运的药物分子在膜两侧的浓度相等时达到动态平衡。 主动转运的特点 ①需要载体，载体对药物有特异性和选择性； ②需要消耗能量； ③受载体转运药物的最大能力的限制，因而有饱和现象； ④同一载体同时转运不同药物时，有竞争性抑制现象； ⑤当膜一侧的药物转运完毕后转运即停止。 如丙磺舒竞争性抑制青霉素类在肾小管分泌，可延长青霉素类药物的作用时间。 Placental Barrier Drugs cross placental barrier primarily by passive diffusion Fat soluble substances cross rapidly and without limitation Placenta is not a barrier to drugs Psychoactive drugs will be present in the fetus at a concentration quite similar to that in the mother 肝药酶(细胞色素P450单氧化酶系) 肝药酶由许多结构和功能类似的细胞色素P450同工酶(cytochrome P450 isozyme，CYP)组成。 CYP的基因和同工酶在人群中具有多态性（polymorphism）。 如: CYP2D6亚型达50多种，其代谢异喹胍的活性的个体差异（individual difference）可达1万倍以上。 D. Drug Excretion 肾脏排泄 脂溶性低、极性大、解离型的药物和代谢产物容易经肾小管排泄。 影响肾脏排泄的因素 尿液pH值 如：弱酸性药物苯巴比妥中毒时，碱化尿液使药物解离度增大，重吸收减少，增加排泄。 竞争性抑制主动分泌通道 有机酸和有机碱主动转运系统 经同一载体转运的药物合用时，可发生竞争性抑制现象。 Fi