《WHO 推荐剂量和更高剂量左氧氟沙星治疗儿童结核病的药代动力学和安全性：一项初步研究》。

Pharmacokinetics and Safety of WHO-Recommended Dosage and Higher Dosage of Levofloxacin for Tuberculosis Treatment in Children: a Pilot Study.

机构信息

Department of Pediatrics, King Chulalongkorn Memorial Hospital, Bangkok, Thailand; Center of Excellence for Pediatric Infectious Diseases and Vaccines, Department of Pediatrics, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.

Queen Sirikit Institute of Child Health, Bangkok, Thailand.

出版信息

Int J Infect Dis. 2022 Sep;122:603-608. doi: 10.1016/j.ijid.2022.07.029. Epub 2022 Jul 13.

DOI:10.1016/j.ijid.2022.07.029

PMID:35842213

Abstract

OBJECTIVES

To evaluate the pharmacokinetic parameters of the 2020 World Health Organization (WHO)-recommended pediatric dosage of levofloxacin and the higher-than-WHO dosage.

METHODS

Children aged 1-15 years with tuberculosis who received levofloxacin-based treatment for at least 7 days were enrolled. First, five children were enrolled to receive the WHO-recommended dosage (15-20 mg/kg/day), then an additional five children received a dosage higher than the WHO-recommended dosage (20-30 mg/kg/day). Blood samples were collected at predose and postdose 1, 2, 4, 6, 8, and 12 hours. A target of the ratio of the free area under the concentration-time curve to minimum inhibitory concentration (fAUC/MIC) was 100.

RESULTS

The median (interquartile range) age was 9.6 (4.9-10.5) and 12.0 (10.1-12.3) years in the WHO dosage and higher-than-WHO dosage groups, respectively. The median (interquartile range) duration of antituberculosis treatment was 24 (8-24) weeks. The geometric mean (95% confidence interval) of fAUC/MIC was 60.4 (43.5-84.0) and 103.2 (70.1-151.8) in the WHO and higher-than-WHO dosage groups, respectively. There was no adverse event of QT prolongation or any other grade 3 or 4 adverse events.

CONCLUSION

Levofloxacin at a higher dose of 20-30 mg/kg/day could achieve the fAUC/MIC target in children.

摘要

目的

评估世界卫生组织（WHO）推荐的儿童左氧氟沙星剂量和高于 WHO 剂量的药代动力学参数。

方法

纳入至少接受 7 天左氧氟沙星为基础的治疗的 1-15 岁结核病儿童。首先，招募了 5 名儿童接受 WHO 推荐剂量（15-20mg/kg/天），然后另外 5 名儿童接受高于 WHO 推荐剂量（20-30mg/kg/天）。在给药前和给药后 1、2、4、6、8 和 12 小时采集血样。游离浓度-时间曲线下面积与最小抑菌浓度比值（fAUC/MIC）的目标比值为 100。

结果

WHO 剂量组和高于 WHO 剂量组的中位（四分位间距）年龄分别为 9.6（4.9-10.5）和 12.0（10.1-12.3）岁。抗结核治疗的中位（四分位间距）持续时间分别为 24（8-24）周。fAUC/MIC 的几何均数（95%置信区间）分别为 WHO 剂量组 60.4（43.5-84.0）和高于 WHO 剂量组 103.2（70.1-151.8）。没有出现 QT 延长或任何其他 3 级或 4 级不良事件。