Dorian C, Cal J C, Cambar J
Pathol Biol (Paris). 1985 May;33(5):377-80.
This study addresses circadian variations in the tolerance of mice to a single lethal dose of amikacin. Female mice placed in cages providing constant thermal conditions and lighted from 8 h to 20 h were given a single intraperitoneal injection of 1.6 to 1.9 g/kg amikacin at different times over the 24 hours (8 h, 14 h, 20 h and 2 h) and in two different seasons (november/december and march/april). The number of dead mice was determined every day for seven consecutive days. For a given dose, mortality rate was influenced by the time and season of administration of amikacin. Amikacin toxicity exhibited a peak at 2 h (mean 60%) and nadir at 14 h (mean 47.75%) in november/december, whereas the opposite was true in spring (means 36.6% and 23.3% respectively at 14 h and 2 h). Thus, acute toxicity of amikacin in mice varies throughout the circadian cycle and from season to season. These findings encourage further research in view of achieving optimal use of antibiotics in human clinical practice.
本研究探讨了小鼠对单次致死剂量阿米卡星耐受性的昼夜变化。将雌性小鼠置于提供恒定热条件且光照时间为8时至20时的笼子中，在24小时内的不同时间点（8时、14时、20时和2时）以及两个不同季节（11月/12月和3月/4月）腹腔注射1.6至1.9g/kg的阿米卡星。连续七天每天测定死亡小鼠的数量。对于给定剂量，阿米卡星的死亡率受给药时间和季节的影响。在11月/12月，阿米卡星毒性在2时出现峰值（平均60%），在14时出现最低点（平均47.75%），而在春季则相反（14时和2时的平均值分别为36.6%和23.3%）。因此，阿米卡星对小鼠的急性毒性在昼夜周期中以及不同季节之间有所变化。鉴于在人类临床实践中实现抗生素的最佳使用，这些发现鼓励进一步研究。
