甲氨喋呤毒性及药动学参数昼夜变化

CIRCADIAN CHANGES IN TOXICITY AND PHARMACOKINETICS OF METHOTREXATE

本文研究甲氨喋呤（ＭＴＸ）对小鼠及大鼠的毒性和药动学参数的昼夜变化，并探讨了两者的关系。ＭＴＸ毒性和药动学均与昼夜用药时间相关，明期用药毒性高，血药浓度曲线下面积大，清除率低；暗期用药相反。提示ＭＴＸ毒性昼夜差异可能与其药动学的昼夜变化有关。

The circadian rhythms in the toxicity and the pharmacokinetica of methotrexate(MTX),as well as the relationship between the chronotoxicity and chronopharmacokinetics of the drug were investigated in mice and rats. Definite circadian rhythms were demonstrated for the toxicity and the kinetica of MTX depending on the time of adminstration with the higher toxicity, smallest clearance and largest AUC at the midlight, lower toxicity, largest clearance and smallest AUC at the middark. Since the chronotoxicity of MTX well coincided with the rhythm in the kinetica of the drug, the change of MTX toxicity seems to be, at least in part, due to the circadian changes in kinetics of the drug.