Does critical illness change levofloxacin pharmacokinetics?

Roberts, Jason A., Cotta, Menino Osbert, Cojutti, Piergiorgio, Lugano, Manuela, Rocca, Giorgio D. and Pea, Federico (2016) Does critical illness change levofloxacin pharmacokinetics?. Antimicrobial Agents and Chemotherapy, 60 3: 1459-1463. doi:10.1128/AAC.02610-15

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Author Roberts, Jason A.
Cotta, Menino Osbert
Cojutti, Piergiorgio
Lugano, Manuela
Rocca, Giorgio D.
Pea, Federico
Title Does critical illness change levofloxacin pharmacokinetics?
Journal name Antimicrobial Agents and Chemotherapy   Check publisher's open access policy
ISSN 1098-6596
Publication date 2016-03-01
Year available 2015
Sub-type Article (original research)
DOI 10.1128/AAC.02610-15
Open Access Status File (Publisher version)
Volume 60
Issue 3
Start page 1459
End page 1463
Total pages 5
Place of publication Washington, DC United States
Publisher American Society for Microbiology
Language eng
Subject 3004 Pharmacology
2736 Pharmacology (medical)
2725 Infectious Diseases
Abstract Levofloxacin is commonly used in critically ill patients for which existing data suggest nonstandard dosing regimens should be used. The objective of this study was to compare the population pharmacokinetics of levofloxacin in critically ill and in non-critically ill patients. Adult patients with a clinical indication for levofloxacin were eligible for participation in this prospective pharmacokinetic study. Patients were given 500 mg or 750 mg daily by intravenous administration with up to 11 blood samples taken on day 1 or 2 of therapy. Plasma samples were analyzed and population pharmacokinetic analysis was undertaken using Pmetrics. Thirty-five patients (18 critically ill) were included. The mean (standard deviation [SD]) age, weight, and Cockcroft-Gault creatinine clearance for the critically ill and for the non-critically ill patients were 60.3 (16.4) and 72.0 (11.6) years, 78.5 (14.8) and 70.9 (15.8) kg, and 71.9 (65.8) and 68.2 (30.1) ml/min, respectively. A two-compartment linear model best described the data. Increasing creatinine clearance was the only covariate associated with increasing drug clearance. The presence of critical illness did not significantly affect any pharmacokinetic parameter. The mean (SD) parameter estimates were as follows: clearance, 8.66 (3.85) liters/h; volume of the central compartment (Vc), 41.5 (24.5) liters; intercompartmental clearance constants from central to peripheral, 2.58 (3.51) liters/h; and peripheral to central compartments, 0.90 (0.58) liters/h. Monte Carlo dosing simulations demonstrated that achievement of therapeutic exposures was dependent on renal function, pathogen, and MIC. Critical illness appears to have no independent effect on levofloxacin pharmacokinetics that cannot be explained by altered renal function.
Keyword Pharmacodynamics
Q-Index Code C1
Q-Index Status Provisional Code
Grant ID APP1048652
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2016 Collection
School of Medicine Publications
School of Pharmacy Publications
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