庆大霉素在小鼠的时辰毒性及时辰药代动力学

本文研究了庆大霉素对小鼠的毒性及其药代动力学的昼夜节律性变化。雄性ICR小鼠自实验前两周置于标准的明期和暗期下饲养,自由进食进水。毒性实验剂量为庆大霉素290mg/kg,Sc:药代动力学实验剂量为45 mg/kg,Sc。结果表明,庆大霉素毒性及药代动力学因用药时间不同呈明显的昼夜节律性变化。明期中点用药毒性最大,血药浓度最高,AUC值最大:暗期用药毒性小,血药浓度低,AUC值小。提示了庆大霉素毒性的昼夜节律变化与其药代动力学的的昼夜节律变化有密切关系。

CIRCADIAN RHYTHMS OF TOXICITY AND PHARMACOKINETICS OF GENTAMICIN IN MICE

The circadian rhythms in the toxicity and the pharmacokinetics of gentamicin were investigated in mice. Male ICR mice were housed in a standardized light-dark cycle (light on: 0700-1900, LD 12: 12) with food and water ad libitum for 2 weeks before experiment. Each animal was given a single dose of gentamicin 290 mg/kg, se. for the toxicity study and 45 mg/kg, sc for the pharmacokinetic study. A definite circadian rhythm was demonstrated for the toxicity and pharmacokinetics of gentamicin depending on the time of administration with the highest toxicity and plasma drug concentration during the light phase and the lowest during the dark phase. The results of the study suggest that there is a correlation between the peak drug levels and toxicity of gentamicin in mice. The circadian rhythm of gentamicin toxicity seems to be, at least in part, due to the circadian rhythm in pharmacokinetics of the drug.