The Influence of Dosage Regimen on Experimental Gentamicin Nephrotoxicity: Dissociation of Peak Serum Levels from Renal Failure

Publisher Website
Google Scholar
Abstract
Peak serum levels of gentamicin were varied in rats by administering a standard nephrotoxic dosage of 40 mg/kg per day in one (QD), two, or three (TID) daily doses. The QD animals had the highest peak serum levels but showed no appreciable increase of serum creatinine concentrations over a lO-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/IOO ml, mean ± SE) was significantly higher than in control rats (0.6 ± 0.01 mg/IOO ml) (P < 0.001). After two days of gentamicin treatment, the renal concentration of gentamicin was 269 ± 77 μg/g in the QD rats and 820 ± 29 μg/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. The results suggest that dose frequency should be considered when data from different laboratories are compared.

This publication has 3 references indexed in Scilit: