Influence of Renal Function and Age on the Pharmacokinetics of Levofloxacin in Patients with Bone and Joint Infections

Abstract

<jats:p>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 &lt;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.</jats:p>

Clinical Efficacy and Safety Analysis of Levofloxacin for the Prevention of Infection after Traumatic Osteoarthrosis and Internal Fixation: Systematic Review and Meta-Analysis

“…19 full papers were reviewed, different reports of the same clinical study and literature inconsistent with the content of this study were excluded, and references of relevant literature were searched to prevent literature omission. Finally, a total of 12 RCTs were included in the study [11][12][13][14][15][16][17][18][19][20][21][22][23][24]. All the retrieval and screening processes were completed by two evaluators independently, and any different opinions were unified through internal discussion (Table 1).…”

Key Factors in Effective Patient-Tailored Dosing of Fluoroquinolones in Urological Infections: Interindividual Pharmacokinetic and Pharmacodynamic Variability

“…In hospitalized elderly patients with varying degrees of renal function, CL CR was again shown to be the main covariate associated with interindividual variability in LEV CL [90]. A prospective population PK study conducted in patients with bone and joint infections demonstrated that age and glomerular filtration rate were covariates related to interindividual variability of CL/F [81]. Critical illness was not a significant variable in altering LEV CL per se, with altered renal function being the determining factor [77,[93][94][95][96].…”

“…Approximately 83% of LEV is excreted in the urine as an unchanged drug, indicating that it primarily undergoes renal elimination [36,39]. Similarly to CIP, population PK modeling has been used in several studies with LEV to estimate the effect of individual PK parameter values in a variety of patient populations and bacterial infections [70,[81][82][83][84][85][86][87][88][89][90][91][92][93] (Table 2). In several studies, CL CR [71,[82][83][84][85][91][92][93], age [70], and race [70] were found to be covariates that influenced the CL of LEV.…”

Model-Informed Precision Dosing of Antibiotics in Osteoarticular Infections

“…19 A patient of periprosthetic knee infection caused by Streptococcus anginosus, was successfully treated by vancomycin (1 g, q12h, iv) and levofloxacin (750 mg, qd, iv) for 4 weeks, and then levofloxacin (750 mg, qd, po) for 2 weeks. 54 In 2020, Eloy et al 55 developed a PPK model of levofloxacin with 59 OAI patients, and the model consisted of a one-compartment model with first-order absorption and elimination. Monte Carlo simulations evaluated the PTA of levofloxacin at a dose of 750 mg, qd, with different ages and renal functions.…”