Abstract
Despite its efficacy and toxicity being exposure-related, levofloxacin pharmacokinetics in patients with bone and joint infections has been poorly described to date, so the possible need for a dose adjustment is unknown in this population. A prospective population pharmacokinetic study was conducted in 59 patients to answer this question. The final model consisted of a one-compartment model with first-order absorption and elimination. Mean parameter estimates (% interindividual variability) were 0.895 h−1 for the absorption rate constant (Ka), 6.10 L/h (40%) for the apparent clearance (CL/F), 90.6 L (25%) for the apparent distribution volume (V/F). Age and glomerular filtration rate (GFR), estimated by the modification of diet in renal disease formula, were related to CL/F by power models, and CL/F was found to increase for increasing GFR and decreasing age. For a similar GFR, the simulated area under the curve (AUC) was 55% higher in 70 years-old patients compared to 30 year-old patients. Based on this model, a 750 mg dose should provide an optimal exposure (AUC/ minimum inhibitory concentration (MIC) ≥100), with the possible exception of patients older than 60 years and with GFR <70 mL/min/m² who may necessitate a dose reduction, and patients with infections caused by bacteria with MIC close to 1 mg/L who may need an increase in the dose.
Highlights
Levofloxacin is a broad spectrum antibiotic belonging to the fluoroquinolone class, and corresponding to the active enantiomer of ofloxacin [1]
A clinical pharmacokinetic/pharmacodynamic (PK/PD) study performed in 134 hospitalized patients with proven skin, respiratory, or complicated urinary tract infection evidenced that patients with area under the curve (AUC)/MIC ratio
The present study investigated the pharmacokinetics of levofloxacin in patients with bone and joint infections
Summary
Levofloxacin is a broad spectrum antibiotic belonging to the fluoroquinolone class, and corresponding to the active enantiomer of ofloxacin [1]. Levofloxacin is a good candidate for the treatment of bone and joints infections, more since doses of 500 and 750 mg per day provided good outcomes [6,7]. It is, well known that fluoroquinolones efficacy is related to the area under the curve/minimum inhibitory concentration against the causative bacteria (AUC/MIC) ratio, with a currently accepted target of around 100–125 [8,9,10,11]. A clinical pharmacokinetic/pharmacodynamic (PK/PD) study performed in 134 hospitalized patients with proven skin, respiratory, or complicated urinary tract infection evidenced that patients with AUC/MIC ratio
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