时间药理学和时间治疗学资料.ppt

时间药理学与临床合理用药 CHRONOPHARMACOLOGY AND RATIONAL MEDICATION 时间药理学Chronopharmacology 研究药物的体内过程和药物效应与机体生物周期的相互关系 生物周期性(bioperiodicity) 机体的功能状态随时间推移所呈现的规律性变化，包括近日节律 (昼夜节律circadian rhythm)和近年节律(circannual rhythm) The distinguish on the effect of drug while using in different time The same disease, same medicine, same dose, take in different time of a day, there are different effect and toxicity. The degree of the difference may be twofold, or even decades times. The revolving circling movement of time which can be compared to the circadian rhythms that regulate the behaviour, physiology and function of living organisms at many biochemical levels. The daily patterns of hormone release result in different body temperatures, pulse and blood pressure depending on the time of the day. This can be applied to the understanding and treatment of disease. Effective treatment must work with the body’s clocks not against them. The evidence suggests the treatment of disease could be improved by giving drugs at carefully selected times of the day. Chronopharmacology aims at achieving optimum drug effect and minimum adverse effect without altering the functioning of the drug in the body. Modern chronopharmacology investigates drug effects as a function of biological timing. 影响药物作用的时间因素 Chronopharmacokinetics Chronopharmacodynamics E=??F(?, C, S) E：药效及毒性作用的强度 ?：常数 ? ：药物的内在活性 C：作用部位的药物浓度 S：机体对药物的反应性 The effect of bioperiodicity on the absorption of medicine 药物吸收与机体节律性的关系 9时与21时口服氨茶碱的血药浓度比较，尽管AUC和t1/2相同，但9时的tmax短；Cmax高 The effect of bioperiodicity on the distribution of medicine 9时与21时口服地西泮的血药浓度比较：9时的Cmax高；tmax短 禁食状态下给药仍然存在这种差异 在静脉注射给药时，仍然表现出这种差异 提示：这种变化与血浆蛋白含量的节律变化有关(地西泮的血浆蛋白结合率为99％) The effect of bioperiodicity on the metabolism of medicine 肝脏酶的活性具有昼夜节律性 肝脏酶活性低时，药物代谢慢，作用维持时间长 肝脏酶活性高时，药物代谢快，作用维持时间短 肾上腺皮质激素的昼夜节律性也会影响药 物代谢(晨后高午后低) The effect of bioperiodicit