INFLUENCE OF DOSAGE REGIMEN ON EXPERIMENTAL GENTAMICIN-NEPHROTOXICITY - DISSOCIATION OF PEAK SERUM LEVELS FROM RENAL-FAILURE

Peak serum levels of gentamicin were varied in rats by administering a standard neprhotoxic dosage of 40 mg/kg per day in 1 (QD), 2 or 3 (TID) daily doses. The QD animals had the highest peak serum levels but showed no appreciable increase of serum creatinine concentrations over a 10 day treatment period. The TID rats had the lowest peak serum levels, but after 10 days of drug administration, the serum creatinine concentration (2.8 .+-. 0.2 mg/100 ml, mean .+-. SE) was significantly higher than in control rats (0.6 .+-. 0.01 mg/100 ml) (P < 0.001). After 2 days of gentamicin treatment, the renal concentration of gentamicin was 269 .+-. 77 .mu.g/g in the QD rats and 820 .+-. 29 .mu.g/g in the TID rats (P < 0.001). In this rat model, the frequency of doses was a more important factor in the development of nephrotoxicity than the peak serum concentration of gentamicin. Dose frequency apparently should be considered when data from different laboratories are compared.