Despite its effcacy and toxicity being exposure-related, levofloxacin pharmacokinetics in\npatients with bone and joint infections has been poorly described to date, so the possible need for a\ndose adjustment is unknown in this population. A prospective population pharmacokinetic study\nwas conducted in 59 patients to answer this question. The final model consisted of a one-compartment\nmodel with first-order absorption and elimination. Mean parameter estimates (% interindividual\nvariability) were 0.895 h-1 for the absorption rate constant (Ka), 6.10 L/h (40%) for the apparent\nclearance (CL/F), 90.6 L (25%) for the apparent distribution volume (V/F). Age and glomerular filtration\nrate (GFR), estimated by the modification of diet in renal disease formula, were related to CL/F by\npower models, and CL/F was found to increase for increasing GFR and decreasing age. For a similar\nGFR, the simulated area under the curve (AUC) was 55% higher in 70 years-old patients compared to\n30 year-old patients. Based on this model, a 750 mg dose should provide an optimal exposure (AUC/\nminimum inhibitory concentration (MIC) -100), with the possible exception of patients older than\n60 years and with GFR <70 mL/min/m2 who may necessitate a dose reduction, and patients with\ninfections caused by bacteria with MIC close to 1 mg/L who may need an increase in the dose.
Loading....