Circadian Variation in the Intracortical Accumulation Kinetics of Tobramycin in Conscious Rats

Abstract

The time-dependent variation in the renal accumulation of aminoglycosides has not been extensively investigated. The aim of the present study was to better characterize the temporal variation in the intracortical accumulation kinetics of tobramycin. Female Sprague-Dawley rats weighing 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 μg/ml over four different periods of the day (02h00–08h00; 08h00–14h00; 14h00–20h00; and 20h00–02h00). As previously reported, the steady-state elevation of serum 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 compared to rats infused at 08h00–14h00 (p < 0.001). The data suggest that the lower rate of tobramycin accumulation during the dark period might be responsible for the lower toxicity obser...