Abstract

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. Conclusion: 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.

Author Details

Authors

• Z.R. Tayab¹
• G. Hochhaus¹
• S. Kaufmann²
• D. Jäger²
• J. Barth²

Departments

• ¹ Department of Pharmaceutics, College of Pharmacy, University of Florida, Gainesville, FL, USA, and
• ² Clinics of the Berufsgenossenschaft Bergmannstrost, Halle, Germany

Address

G. Hochhaus, PhD
P.O. Box 100494
Department of Pharmaceutics
College of Pharmacy, JHMHC
University of Florida
Gainesville, FL 32610, USA
Email: [email protected]

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