[Chronotoxicity of amikacin]

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.