Do intensive care patients need an individualized dosing regimen for levofloxacin?
OBJECTIVE
In general, the pharmacokinetics (PK) of antibiotics in intensive care unit (ICU) patients are known to differ from healthy subjects. These differences can pose challenges in developing appropriate dosing guidelines. The primary objective of this report was to characterize the disposition of levofloxacin in critically ill patients and to assess any relationships between patient covariates and the PK parameters.


METHODS
20 patients in the ICU were given levofloxacin, 500 mg, as an i.v. infusion for a half hour. Plasma samples were taken until 24 hours and assayed using HPLC. The concentration-time data were analyzed using population analysis with NONMEM.


RESULTS
The data were described using a 2-compartment model. Creatinine clearance was determined to be a statistically significant predictor of variability in total levofloxacin clearance. For patients with higher levofloxacin clearance, the resulting efficacy for different strains of bacteria (expressed as free AUC/MIC ratios) suggested that for less sensitive pathogens, a dosage adjustment may be needed.


CONCLUSIONS
A model describing the pharmacokinetics of levofloxacin in critically ill patients was developed. It was determined that creatinine clearance has a significant role in the disposition of levofloxacin. This may have significant implications in the clinical setting for identifying optimal dosage regimens for ICU patients.
Tayab
Z R
ZR
Department of Pharmaceutics, College of Pharmacy, University of Florida, Gainesville, FL 32610, USA.
Hochhaus
G
G
Kaufmann
S
S
Jäger
D
D
Barth
J
J
D000900:Anti-Bacterial Agents / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D016638:Critical Illness / Q000628:therapy*; D005260:Female; D006801:Humans; D007362:Intensive Care Units; D064704:Levofloxacin; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D015242:Ofloxacin / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D010195:Pancreatitis / Q000188:drug therapy / Q000378:metabolism; D018410:Pneumonia, Bacterial / Q000188:drug therapy / Q000378:metabolism; D018805:Sepsis / Q000188:drug therapy / Q000378:metabolism
D000900:Anti-Bacterial Agents; D064704:Levofloxacin; D015242:Ofloxacin