Pharmacokinetic variability of extended interval tobramycin in burn patients

Background: Aminoglycosides are mandatory in the treatment of severe infections in burns. However, their pharmacokinetics are difficult to predict in critically ill patients. Our objective was to describe the pharmacokinetic parameters of high doses of tobramycin administered at extended intervals in severely burned patients. Methods: We prospectively enrolled 23 burned patients receiving tobramycin in combination therapy for Pseudomonas species infections in a burn ICU over 2 years in a therapeutic drug monitoring program. Trough and post peak tobramycin levels were measured to adjust drug dosage. Pharmacokinetic parameters were derived from two points first order kinetics. Results: Tobramycin peak concentration was 7.4 (3.1-19.6) mu g/ml and C-max/MIC ratio 14.8 (2.8-39.2). Half-life was 6.9 (range 1.8-24.6) h with a distribution volume of 0.4 (0.2-1.0) l/kg. Clearance was 35 (14-121) ml/min and was weakly but significantly correlated with creatinine clearance. Conclusion: Tobramycin had a normal clearance, but an increased volume cf distribution and a prolonged half-life in burned patients. However, the pharmacokinetic parameters of tobramycin are highly variable in burned patients. These data support extended interval administration and strongly suggest that aminoglycosides should only be used within a structured pharmacokinetic monitoring program. (C) 2007 Elsevier Ltd and ISBI. All rights reserved.