DAY-NIGHT TREATMENT DIFFERENCE OF TOBRAMYCIN SERUM AND INTRARENAL DRUG DISTRIBUTION AND NEPHROTOXICITY IN RATS - EFFECTS OF FASTING

The effects of short-term food deprivation on the serum and renal dist ribution and nephrotoxicity of tobramycin were studied in female Sprag ue-Dawley rats maintained on a 14-h light/10-h dark cycle (light on: 0 6:00). For the distribution study, a single injection of tobramycin (4 0 mg/kg, i.p.) was administered at 14:00 or 02:00 to normally fed anim als or to animals fasted for 12 h before tobramycin injection; these t reatment times correspond to the peak and trough of tobramycin nephrot oxicity as previously determined in other studies. The serum and corti cal levels of tobramycin were significantly higher 60, 120, and 240 mi n after the injection in fasted animals treated at 02:00 compared with normally fed animals treated at the same time (p < 0.05). In animals injected at 14:00, similar levels of tobramycin were measured in both fasted and fed rats. In the nephrotoxicity study, female Sprague-Dawle y rats were fasted for 12 h before and 24 h after the timed single inj ection of tobramycin (150 mg/kg, i.p.). The 24-h urinary excretion of beta-galactosidase was significantly higher in fasted animals treated at 02:00 than in fed rats treated at the same time of day. Seventy-two hours following tobramycin injection, serum creatinine levels and cor tical levels of tobramycin were significantly higher in fasted rats tr eated at 14:00 than at 02:00 and in fed rats treated at 14:00. These d ata suggest that a short period of food deprivation modulates the temp oral variations of tobramycin nephrotoxicity.