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-darkcycle(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.