Population pharmacokinetics and dose optimization of intravenous levofloxacin in hospitalized adult patients

Abstract

Although levofloxacin has been used for the last 25 years, there are limited pharmacokinetic data to guide levofloxacin dosing in adult patients. This study aimed to develop a population pharmacokinetic model of levofloxacin for adult hospitalized patients and define dosing regimens that attain pharmacokinetic/pharmacodynamic target associated with maximum effectiveness. Blood samples were drawn from 26 patients during one dosing interval. Population pharmacokinetic modelling and dosign simulations were performed using Pmetrics®. Pathogen minimum inhibition concentration (MIC) distribution data from the European Committee on Antimicrobial Susceptibility Testing database was used to analyse fractional target attainment (FTA). A two-compartment model adequately described the data. The final model included estimated glomerular filtration rate (eGFR) to describe clearance. The population estimate for clearance was 1.12 L/h, while the volume of distribution in the central compartment and peripheral compartments were 27.6 L and 28.2 L, respectively. Our simulation demonstrated that an area under free concentration–time curve to MIC ≥ 80 was hardly achieved for pathogens with MIC ≥ 1 mg/L. Low FTA against Pseudomonas aeruginosa and Streptococcus pneumoniae were observed for patients with higher eGFR (≥ 80 mL/min/1.73m2). A daily levofloxacin dose of 1000 mg is suggested to maximise the likelihood of efficacy for adult patients.

Population pharmacokinetics and dose optimization of levofloxacin in elderly patients with pneumonia

“…In this study, eGFR was the only covariate that had a significant impact on the model, which is consistent with the findings of Cojutti et al 15 and Setiawan et al 16 Levofloxacin is almost not metabolized in the body and is primarily eliminated through the kidneys in its unchanged form via urine. Approximately 79‐87% of the drug is eliminated in the urine 14,17,18 …”

“…Based on the results of levofloxacin dose simulations, when using levofloxacin for empirical treatment of pneumonia in the elderly, a recommended dosing regimen is 750 mg once daily. Other related studies have also shown that a dosing regimen of 750 mg once daily with levofloxacin leads to good clinical outcomes and is well‐tolerated 16,23–28 …”

“…Other related studies have also shown that a dosing regimen of 750 mg once daily with levofloxacin leads to good clinical outcomes and is well-tolerated. 16,[23][24][25][26][27][28] This study also has some limitations. It has been suggested that body weight is one of the factors influencing the clearance rate of levofloxacin.…”

Amphotericin B- and Levofloxacin-Loaded Chitosan Films for Potential Use in Antimicrobial Wound Dressings: Analytical Method Development and Its Application

“…These data indicated that the chitosan films we developed in this study could serve for localized topical use as the systemic exposure (indicated by the permeation data) is likely to be minimal, indicating good safety profiles, especially for toxic drugs such as AMB [71]. Even though there are very limited resources to define concentration toxicity threshold for levofloxacin [72,73], the safety profile of levofloxacin has been widely reported in the literature and a high daily dose of 1000 mg is recommended for patients [74]. The deposition and permeation of LVX from the film (approximately 21.54 µg in total) should be tolerable [75].…”

Community-acquired pneumonia: antibiotic therapy approach after the COVID-19 pandemic. A review

“…С учетом нарастающей в Российской Федерации резистентности и ростом МПК 90 оптимальная доза перорального амоксициллина -750-1000 мг на прием, препарат принимается 3 раза в сутки [19,20]. При аллергии на β-лактамы надежной альтернативой являются рФХ (моксифлоксацин 400 мг, левофлоксацин не менее 500 мг 2 раза в сутки) [1,4,7,14,[18][19][20][46][47][48][49][50]. Применение левофлоксацина оправдано в случаях высокой вероятности синегнойной инфекции, например у лиц с тяжелой ХОБЛ и/или бронхоэктазами при непереносимости β-лактамов, в том числе карбапенемов.…”