Population pharmacokinetics of levofloxacin in drug-susceptible and drug-resistant tuberculosis patients: Optimal dose suggestion based on renal function

IF 2.9 3区医学 Q3 IMMUNOLOGY

Tuberculosis Pub Date : 2025-07-23 DOI:10.1016/j.tube.2025.102675

Yong-Soon Cho , Rannissa Puspita Jayanti , Hyun-Kyung Lee , Hyo-Jung Kim , Tae Won Jang , Yun Seok Kim , Yousang Ko , Jinsoo Min , Heayon Lee , Soedarsono Soedarsono , Hyeon-Jeong Seong , Young-Kyung Choi , Ho-Sook Kim , Dong Hyun Kim , Jae-Gook Shin , cPMTb

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引用次数: 0

Abstract

Background

Levofloxacin (LFX) has gained attention as an effective drug to reduce treatment duration in tuberculosis (TB). We aimed to evaluate factors related to interindividual variability (IIV) and describe the pharmacokinetics (PK) of LFX in both DS- and DR-TB, as well as explore the optimal dose for TB treatment.

Methods

We included demographics, clinical information, and LFX concentrations from multinational hospitals. All data were utilized for model establishment. The population PK model was built using nonlinear mixed-effects method. Dose simulation was carried out thereafter using Monte Carlo simulation.

Results

A one-compartment model with allometric scaling described LFX PK adequately. PK parameters were similar between DS- and DR-TB. eGFR significantly affected CL/F, which decreased by 22 % and 48 % in mild and moderate-severe renal impairment, respectively (normal CL/F: 6.6 L/h). Considering LFX's AUC/MIC target of 146 and epidemiological cut-off value of MIC 0.5 μg/mL, doses of 1000 mg, 1250 mg, and 1500 mg may achieve 90 % probability of target attainment in patients with normal renal function weighing <40 kg, 40–70 kg, and >70 kg, respectively.

Conclusion

Renal impairment reduced LFX clearance. Doses equal to or greater than 1000 mg may improve AUC/MIC target attainment but require cautious use considering safety and clinical efficacy.

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左氧氟沙星在药敏和耐药结核病患者中的群体药动学：基于肾功能的最佳剂量建议

背景：左氧氟沙星（LFX）作为一种缩短结核病（TB）治疗时间的有效药物已引起人们的关注。我们的目的是评估与个体间变异性（iv）相关的因素，描述LFX在DS- TB和DR-TB中的药代动力学（PK），并探索治疗TB的最佳剂量。方法我们纳入了来自跨国医院的人口统计、临床信息和LFX浓度。所有数据均用于模型建立。采用非线性混合效应方法建立种群PK模型。随后采用蒙特卡罗模拟方法进行剂量模拟。结果异速缩放的单室模型充分描述了LFX的PK。DS- tb和DR-TB的PK参数相似。eGFR显著影响CL/F，轻度和中重度肾功能损害患者CL/F分别下降22%和48%（正常CL/F: 6.6 L/h）。考虑到LFX的AUC/MIC目标值为146，MIC的流行病学临界值为0.5 μg/mL，对于体重为40 kg、40 - 70 kg和70 kg的肾功能正常患者，1000mg、1250mg和1500mg的剂量分别有90%的概率达到目标。结论肾功能损害可降低LFX清除率。剂量等于或大于1000mg可能改善AUC/MIC目标的实现，但考虑到安全性和临床疗效，需要谨慎使用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Tuberculosis 医学-呼吸系统

CiteScore

4.60

自引率

3.10%

发文量

审稿时长

49 days

期刊介绍： Tuberculosis is a speciality journal focusing on basic experimental research on tuberculosis, notably on bacteriological, immunological and pathogenesis aspects of the disease. The journal publishes original research and reviews on the host response and immunology of tuberculosis and the molecular biology, genetics and physiology of the organism, however discourages submissions with a meta-analytical focus (for example, articles based on searches of published articles in public electronic databases, especially where there is lack of evidence of the personal involvement of authors in the generation of such material). We do not publish Clinical Case-Studies. Areas on which submissions are welcomed include: -Clinical TrialsDiagnostics- Antimicrobial resistance- Immunology- Leprosy- Microbiology, including microbial physiology- Molecular epidemiology- Non-tuberculous Mycobacteria- Pathogenesis- Pathology- Vaccine development. This Journal does not accept case-reports. The resurgence of interest in tuberculosis has accelerated the pace of relevant research and Tuberculosis has grown with it, as the only journal dedicated to experimental biomedical research in tuberculosis.