CIRCADIAN VARIATION IN THE INTRACORTICAL ACCUMULATION KINETICS OF TOBRAMYCIN IN CONSCIOUS RATS

The time-dependent variation in the renal accumulation of aminoglycosi des has not been extensively investigated. The aim of the present stud y was to better characterize the temporal variation in the intracortic al accumulation kinetics of tobramycin. Female Sprague-Dawley rats wei ghing 210-254 g were maintained in a 14 h light/10 h dark cycle (light on 06h00-20h00). They were infused for 6 h with tobramycin to achieve individual steady-state serum levels of 0.5-15 mu g/ml over four diff erent periods of the day (02h00-08h00; 08h00-14h00; 14h00-20h00; and 2 0h00-02h00). As previously reported, the steady-state elevation of ser um tobramycin concentrations was associated with a linear increase of the cortical concentration in all groups. The tobramycin accumulation rate was significantly lower in animals infused at 20h00-02h00 compare d to rats infused at 08h00-14h00 (p < 0.001). The data suggest that th e lower rate of tobramycin accumulation during the dark period might b e responsible for the lower toxicity observed during this time.