时间药理学与临床合理用药

：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
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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
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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.
Chronopharmacology aims at achieving optimum drug effect and minimum adverse effect without altering the functioning of the drug in the body.
Modern
chronopharmacology
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.
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The effect of bioperiodicity on the 肝脏酶的m活e性ta具b有ol昼ism夜节of律m性edicine
❖ 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)
时间药理学与临床合理用药
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)
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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(地百度文库泮的血浆蛋白结合率为99％)
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抗高血压药物对血压昼夜节律的影响
investigates drug effects as a function of
biological timing.
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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
corresponds to 10 A.M. and 2 P.M., the alkaline tide after meals.
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The effect of bioperiodicity on the pharmacodynamics
❖ 胆固醇合成酶系统夜间合成增加；
❖ 甲基戊二酰辅酶A还原酶抑制剂可抑制 胆固醇的合成，药物效应也体现出相应 的昼夜节律；
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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.
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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.
❖ 黎明前肾上腺素和cAMP浓度低下，哮喘 发作加重；晚饭后一次给予茶碱缓释剂， 可明显减轻哮喘的夜间发作
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时间药理学 对临床药物治疗的指导作用
时间治疗法(chronotherapy) ❖硝苯地平对心肌缺血昼夜节律的影响
对纠正6时~12时的心肌缺血作用强 对纠正21时~24时的心肌缺血作用弱 ❖阿司匹林对心肌梗死昼夜节律的影响 隔日服用对6时~9时的心梗发作有明显疗 效；对其他时段的作用弱
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The effect of bioperiodicity on the excretion of medicine
The rhythm of the acid and base flow of the urine ❖The most acid at 2:00 A.M. (pH 5.0 to 6.8) ❖The most alkaline at 2:00 P.M. (pH 7.0 to 8.5) ❖Two times a day the urine should be alkaline