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目的研究XK对小鼠的急性毒性、药效学及药动学的昼夜节律性。方法小鼠分别在0400、0800、1200、1600、2000和2400灌胃XK后,观察其急性死亡率,用热板法、扭体法了解XK镇痛作用的时间变化,同时用高效液相色谱法测定不同时间点的血药浓度。结果XK对小鼠的急性毒性呈明显的昼夜节律,毒性作用的峰值在明中期;镇痛作用存在昼夜节律性差异,但作用峰值在明中后期,这恰是血药浓度的达峰时间。结论XK有良好的镇痛作用,其急性毒性和镇痛作用均呈现昼夜节律性,急性毒性与血药浓度的昼夜节律性有关。
Objective To study the acute toxicity, pharmacodynamics and pharmacokinetic circadian rhythm of XK in mice. Methods Mice were administrated with XK at 0400, 0800, 1200, 1600, 2000 and 2400 respectively. The acute mortality was observed. The time course of XK analgesia was determined by hot plate method and writhing method. Simultaneously, high performance liquid chromatography was used. The method determines the blood drug concentration at different time points. Results The acute toxicity of XK to mice was obvious circadian rhythm. The peak of toxic effect was in the mid-Ming period. There was a circadian rhythm difference in analgesic effect, but the peak effect was in the late Ming and late period, which was the peak time of blood drug concentration. Conclusion XK has good analgesic effect, and its acute toxicity and analgesic effect all show circadian rhythm. Acute toxicity is related to circadian rhythm of blood drug concentration.