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

作者：Watsamon Jantarabenjakul, Piyarat Suntarattiwong, Noppadol Wacharachaisurapol, Praon Supradish Na Ayudhya, Weeraya Phaisal, Monta Tawan, Juthamanee Moonwong, Tavitiya Sudjaritruk, Pajaree Chariyavilaskul, Thanyawee Puthanakit · 发表于：International Journal of Infectious Diseases · 年份：2022 · DOI：10.1016/j.ijid.2022.07.029 · 被引用次数：9 · 研究领域：Tuberculosis Research and Epidemiology、Antibiotics Pharmacokinetics and Efficacy、Pneumonia and Respiratory Infections

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.