title: Does Critical Illness Change Levofloxacin Pharmacokinetics?
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.
authors.affiliation: Burns, Trauma, and Critical Care Research Centre, The University of Queensland, Brisbane, Queensland, Australia School of Pharmacy, The University of Queensland, Brisbane, Queensland, Australia Pharmacy Department, Royal Brisbane and Womens' Hospital, Brisbane, Queensland, Australia j.roberts2@uq.edu.au.
authors.forename: Jason A
authors.initials: JA
authors.lastname: Roberts
authors.affiliation: Burns, Trauma, and Critical Care Research Centre, The University of Queensland, Brisbane, Queensland, Australia School of Pharmacy, The University of Queensland, Brisbane, Queensland, Australia Pharmacy Department, Royal Brisbane and Womens' Hospital, Brisbane, Queensland, Australia.
authors.forename: Menino Osbert
authors.initials: MO
authors.lastname: Cotta
authors.affiliation: Institute of Clinical Pharmacology, Azienda Ospedaliero-Universitaria Santa Maria della Misericordia, Udine, Italy Department of Experimental and Clinical Medical Sciences, University of Udine, Udine, Italy.
authors.forename: Piergiorgio
authors.initials: P
authors.lastname: Cojutti
authors.affiliation: Department of Anesthesia and Intensive Care Medicine, University of Udine, Udine, Italy.
authors.forename: Manuela
authors.initials: M
authors.lastname: Lugano
authors.affiliation: Department of Anesthesia and Intensive Care Medicine, University of Udine, Udine, Italy.
authors.forename: Giorgio
authors.initials: G
authors.lastname: Della Rocca
authors.affiliation: Institute of Clinical Pharmacology, Azienda Ospedaliero-Universitaria Santa Maria della Misericordia, Udine, Italy Department of Experimental and Clinical Medical Sciences, University of Udine, Udine, Italy.
authors.forename: Federico
authors.initials: F
authors.lastname: Pea
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D016638:Critical Illness; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D064704:Levofloxacin / Q000008:administration & dosage / Q000493:pharmacokinetics*; D008297:Male; D008657:Metabolic Clearance Rate; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D008962:Models, Theoretical; D009010:Monte Carlo Method; D018410:Pneumonia, Bacterial / Q000188:drug therapy; D011552:Pseudomonas Infections / Q000188:drug therapy / Q000382:microbiology; D011550:Pseudomonas aeruginosa / Q000187:drug effects
chemical_list: D000900:Anti-Bacterial Agents; D064704:Levofloxacin