Population pharmacokinetics of aminoglycosides in critically ill trauma patients on once-daily regimens.
BACKGROUND
Once-daily dosing regimens of aminoglycosides are routinely used in critically ill trauma patients. However, the pharmacokinetic parameters 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 patient. Population pharmacokinetic parameters were estimated on the basis of a one-compartment structural model and the program nonlinear mixed effects modeling.


RESULTS
Fifty-three aminoglycoside concentrations from 19 patients were analyzed. The aminoglycoside clearance was 5.47 L/h. The mean volume of distribution was 22.2 L (0.3 L/kg). The mean half-life was 2.9 hours. Serum-aminoglycoside concentrations were undetectable for longer than 12 hours in 4 of 19 patients. Weight, age, or serum creatinine did not significantly explain the variability.


CONCLUSIONS
There is marked variability in aminoglycoside pharmacokinetic parameters in critically ill trauma patients. This may lead to prolonged drug-free intervals. Individualized dosing of critically ill trauma patients on the basis of at least two serum-aminoglycoside concentrations seems indicated when using once-daily dosing regimens.
Barletta
J F
JF
Department of Pharmacy Practice, University of Arizona Health Sciences Center, Tucson, USA. jbarlett@dmc.org
Johnson
S B
SB
Nix
D E
DE
Nix
L C
LC
Erstad
B L
BL
D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D001835:Body Weight; D003404:Creatinine / Q000097:blood; D016638:Critical Illness; D004334:Drug Administration Schedule; D016903:Drug Monitoring; D005839:Gentamicins / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D006801:Humans; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D009104:Multiple Trauma / Q000188:drug therapy* / Q000378:metabolism; D017711:Nonlinear Dynamics; D011446:Prospective Studies; D013997:Time Factors; D014018:Tissue Distribution; D014031:Tobramycin / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*
D000900:Anti-Bacterial Agents; D005839:Gentamicins; D003404:Creatinine; D014031:Tobramycin