Greenberg Rachel G, Landersdorfer Cornelia B, Rivera-Chaparro Nazario, Harward Melissa, Conrad Thomas, Nakamura Aya, Kirkpatrick Carl M, Gu Kenan, Ghazaryhan Varduhi, Osborn Blaire, Walter Emmanuel B
Duke Clinical Research Institute, Duke University School of Medicine, 300 W. Morgan St, Durham, NC, 27701, USA.
Department of Pediatrics, Duke University School of Medicine, Durham, NC, USA.
Paediatr Drugs. 2022 Mar;24(2):163-173. doi: 10.1007/s40272-022-00493-3. Epub 2022 Mar 14.
BACKGROUND/OBJECTIVE: Moxifloxacin is a fluoroquinolone that is commonly used in adults, but not children. Certain clinical situations compel pediatric clinicians to use moxifloxacin, despite its potential for toxicity and limited pharmacokinetics (PK) data. Our objective was to further characterize the pharmacokinetics of moxifloxacin in children.
We performed an opportunistic, open-label population PK study of moxifloxacin in children < 18 years of age who received moxifloxacin as part of standard care. A set of structural PK models and residual error models were explored using nonlinear mixed-effects modeling. Covariates with known biological relationships were investigated for their influence on PK parameters.
We obtained 43 moxifloxacin concentrations from 14 participants who received moxifloxacin intravenously (n = 8) or orally (n = 6). The dose of moxifloxacin was 10 mg/kg daily in participants ≤ 40 kg and 400 mg daily in participants > 40 kg. The population mean clearance and mean volume of distribution were 18.2 L/h and 167 L, respectively. The oral absorption was described by a first-order process. The estimated extent of oral bioavailability was highly variable (range 20-91%). Total body weight was identified as a covariate on clearance and volume of distribution, and substantially reduced the random unexplained inter-individual variability for both parameters. No participants experienced suspected serious adverse reactions related to moxifloxacin.
These data add to the existing literature to support use of moxifloxacin in children in certain situations; however, further prospective studies on the safety and efficacy of moxifloxacin are needed.
背景/目的：莫西沙星是一种常用于成人而非儿童的氟喹诺酮类药物。尽管其具有潜在毒性且药代动力学（PK）数据有限，但某些临床情况迫使儿科临床医生使用莫西沙星。我们的目的是进一步描述莫西沙星在儿童中的药代动力学特征。
我们对接受莫西沙星作为标准治疗一部分的18岁以下儿童进行了一项机会性、开放标签的群体PK研究。使用非线性混合效应模型探索了一组结构PK模型和残差误差模型。研究了具有已知生物学关系的协变量对PK参数的影响。
我们从14名接受静脉注射（n = 8）或口服（n = 6）莫西沙星的参与者中获得了43个莫西沙星浓度。体重≤40 kg的参与者中莫西沙星剂量为每日10 mg/kg，体重>40 kg的参与者中莫西沙星剂量为每日400 mg。群体平均清除率和平均分布容积分别为18.2 L/h和167 L。口服吸收采用一级过程描述。估计的口服生物利用度范围变化很大（20%-91%）。总体重被确定为清除率和分布容积的协变量，并显著降低了这两个参数的个体间随机 unexplained 变异性。没有参与者经历与莫西沙星相关的疑似严重不良反应。
这些数据补充了现有文献，支持在某些情况下儿童使用莫西沙星；然而，需要进一步对莫西沙星的安全性和有效性进行前瞻性研究。
