Population pharmacokinetics of aminoglycosides in critically ill trauma patients on once-daily regimens

Background: Once-daily dosing regimens of aminoglycosides are routinely use d in critically ill trauma patients. However, the pharmacokinetic parameter s are variable in these patients. The purpose of this study was to evaluate the pharmacokinetics of aminoglycosides in critically ill trauma patients receiving once-daily dosing regimens. Methods: At least two aminoglycoside concentrations were measured in each p atient, Population pharmacokinetic parameters were estimated on the basis o f a one-compartment structural model and the program nonlinear mixed effect s modeling. Results: Fifty-three aminoglycoside concentrations from 19 patients were an alyzed. The aminoglycoside clearance was 5.47 L/h, The mean volume of distr ibution was 22.2 L (0.3 L/kg). The mean half-life was 2.9 hours. Serum-amin oglycoside concentrations were undetectable for longer than 12 hours in 4 o f 19 patients. Weight, age, or serum creatinine did not significantly expla in the variability. Conclusion: There is marked variability in aminoglycoside pharmacokinetic p arameters in critically ill trauma patients. This may lead to prolonged dru g-free intervals. Individualized dosing of critically ill trauma patients o n the basis of at least two serum-aminoglycoside concentrations seems indic ated when using once-daily dosing regimens.