曲马多在小鼠体内的时间药理学

目的　研究曲马多对小鼠的急性毒性、药效学及药代动力学的昼夜节律性。方法　小鼠在08:00 ,12:00 ,16:00,20:00 ,24:00和04:00 ip曲马多后,观察其急性死亡率、对热板和压尾刺激的反应及药代动力学的变化。结果曲马多对小鼠的急性毒性有明显的昼夜节律,且与血药浓度的昼夜节律呈正相关,毒性作用峰值在暗中期;曲马多对小鼠的镇痛作用存在昼夜节律性差异,作用峰值在暗后期;曲马多在小鼠体内的药代动力学有用药时间依赖性。结论　曲马多对小鼠的急性毒性、镇痛作用及药动学均存在昼夜节律性

CHRONOPHARMACOLOGY OF TRAMADOL IN MICE

AIM To investigate the influence of dosing time on acute toxicity, action and pharmacokinetics of tramadol in mice to find the circadian rhythms of the drug. METHODS Tramadol was given (ip) to mice at 08:00 , 12:00 , 16:00 , 20:00 , 24:00 , 04:00 and the variations of their acute mortality, responses to hot plate and tail pressing stimulation and pharmacokinetics were investigated. RESULTS Significant circadian rhythm was found for the acute toxicity of tramadol in mice and the highest mortality was found when the drug was administered in the middle dark phase. The rhythm of drug toxicity coincided nicely with the rhythm of plasma drug level. Tramadol effect was demonstrated to vary circadianly and the highest effect occurred in the late dark phase. Dosing time dependent kinetics of tramadol was also found in mice. CONCLUSION Significant circadian rhythm of the acute toxicity, action and pharmacokinetics was found in mice when tramadol was given at different times of the day.