Influence of Renal Function and Age on the Pharmacokinetics of Levofloxacin in Patients with Bone and Joint Infections
Gauthier Eloy, David Lebeaux, Manon Launay, Marie‐Paule Fernandez‐Gerlinger, Eliane M. Billaud, Emmanuel Douez, Jean‐Luc Mainardi, Benjamin Bouyer, Vincent Jullien
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.