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)microg/ml and Cmax/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.


CONCLUSIONS
Tobramycin had a normal clearance, but an increased volume of 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.
Bracco
David
D
Montreal Burn Centre, Montreal University Hospital, Campus Hotel Dieu, Montreal, Canada. David.Bracco@McGill.Ca
Landry
Christine
C
Dubois
Marc-Jacques
MJ
Eggimann
Philippe
P
D000328:Adult; D000368:Aged; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D002056:Burns / Q000150:complications*; D003404:Creatinine / Q000097:blood; D003422:Critical Care / Q000379:methods; D016638:Critical Illness / Q000628:therapy; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D016903:Drug Monitoring / Q000379:methods; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D011552:Pseudomonas Infections / Q000188:drug therapy / Q000378:metabolism*; D014031:Tobramycin / Q000008:administration & dosage / Q000493:pharmacokinetics*; D016896:Treatment Outcome; D014946:Wound Infection / Q000188:drug therapy / Q000378:metabolism*
D000900:Anti-Bacterial Agents; D003404:Creatinine; D014031:Tobramycin