An approach to forecast aminoglycoside-related nephrotoxicity from routinely collected clinical data

Routinely collected clinical data on 104 critically ill patients who had received an aminoglycoside (gentamicin or tobramycin) were evaluated using a proposed approach to forecast aminoglycoside-related nephrotoxicity. Observed steady-state peak and trough concentrations were greater than the respective predicted values when one-compartment model was assumed. This difference was particularly eminent for trough concentrations. The bias (difference between predicted and observed values) for trough concentrations was analyzed assuming tissue accumulation by an extended least-squares method to estimate population pharmacokinetics. The mean values for terminal half-life of gentamicin and tobramycin in patients who did not develop nephrotoxicity were estimated to be approximately 50 and 116 h, respectively. By using these values, the bias of trough concentration was found to be greater in patients who developed nephrotoxicity during or within 60 days after the therapy than in those who did not. Our results suggest that assessing the bias of steady-state trough concentrations of aminoglycosides can provide a useful index to forecast an aminoglycoside-induced nephrotoxicity.