苯巴比妥对小鼠的敏感性及药物代谢动力学的昼夜差异

苯巴比妥对ICR小白鼠的急性毒性及药效均呈明显的昼夜节律性差异,夜间用药的毒性高于白昼用药,死亡峰值时在21:29,反之,白昼用药催眠作用起效快,维持时间久,血药浓度高,半衰期短,在较低的血药浓度下仍能维持有效的催眠作用,结果表明苯巴比妥的毒性及药效的昼夜节律性差异并非完全取决于其药物动力学的昼夜差异,而可能是主要依赖于动物的敏感性的昼夜差异。

Circadian variations of susceptibility and pharmacokinetics of phenobarbital in mice

The circadian variations in the susceptibility and the pharmacokinetics of phenobarbital were investigated in mice. Male ICR mice were housedunder a standardized light-dark cycle condition (light at 07 : 00-19 : 00, L : D= 12 : 12 h) with food and water ad libitum for 2 wk before th experiment. Defi nite circadian rhythms were demonstrated for the toxicity and the effectiveness of phenobarbital depending on the time of drug administration. A higher mortality was found during the dark phase with acrophase at 21 : 29. The hypnotic action of the drug was higher at the light phase when compared with the dark phase. However, the drug concentrations in plasma were higher and the half-life period was shorter at the light phase. Since there was a low correlationcoefficient between the chronosusceptibility and the chronopharmacokinetics of the drug, it suggests that the circadian variations of phenobarbital chronergy seem to be mainly attributed to the circadian changes of the susceptibility of the animals to the drug.