02药物代谢动力学 PBL2.ppt

药物代谢动力学Pharmacokinetics; Pharmacokinetics-- 主要研究机体对药物的影响，即药物进入机体后的体内过程，就是机体对药物的处置过程。 吸收(absorption)-------drug’s 转运 分布(distribution)-----drug’s 转运 代谢(metabolism) -----drug’s 转化 排泄(excretion) -------drug’s 转运 ;游离;一、药物的跨膜转运（transmembrane transport） 1.滤过、简单扩散、载体转运、膜动转运;pKa的含义 当解离和不解离的药物相等时，即当药物解离一半时，溶液的pH是该药的pKa，每个药物都有自己的pKa值。 ;pKa;;弱酸性药物丙磺舒pKa=3.4;2、药物的浓度差以及细胞膜通透性、面积和厚度 3、Blood flow 4、细胞膜转运蛋白的量和功能drug transportation;Parenteral (IV); Oral Administration (P. O.) The drug is swallowed. The stomach dissolves the drug. The drug is passed into the small intestine. Drug is absorbed through mucous membranes and enters the blood capillaries. Factors determining rate of absorption Food in G.I. Tract. Lipid Solubility of the Drug pH of drug and environment can affect lipid solubility. ;;Orally administered drugs reach the liver before the brain. First-pass metabolism. ;;Advantages of oral drug administration: Easy Disadvantages of oral drug administration: Slow Absorption Drug Depot Acidic GI environment. First-Pass Metabolism GI Irritation ; Administration through injection (IV, IM, SubQ) Advantages No harsh GI environment. Controlled onset of effects. Rapid onset (IV). Less rapid (IM, SubQ). Disadvantages Risk of overdose (IV). Risk of infectious disease. Tissue Damage.;Administration through inhalation Advantages Most rapid effect. Disadvantages Overdose Potential Throat and lung irritation. Potential dose variability.;Other routes of administration: Topical application to the skin. Application to nasal, oral, or rectal membranes. ;Differences in release profiles of medications. Most medications are “Immediate Release”. “Delayed Release” oral meds prevent stomach irritation. “Extended Release” preparations are a newer phenomenon. New formulations of an old product Often accomplished by layering. Extended release also found in non oral meds.;2. 分布（distribution） Heart pumps the blood throughout the body. Drugs diffuse out of capillar