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.

Methods

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.

Results

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.

Conclusion

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.

中文翻译：

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莫西沙星在儿童中的群体药代动力学

背景/目标

莫西沙星是一种氟喹诺酮类药物，常用于成人，但不用于儿童。某些临床情况迫使儿科临床医生使用莫西沙星，尽管它具有潜在的毒性和有限的药代动力学 (PK) 数据。我们的目标是进一步表征莫西沙星在儿童中的药代动力学。

方法

我们在接受莫西沙星作为标准治疗一部分的 18 岁以下儿童中进行了一项关于莫西沙星的机会性、开放标签人群 PK 研究。使用非线性混合效应建模探索了一组结构 PK 模型和残余误差模型。研究了具有已知生物学关系的协变量对 PK 参数的影响。

结果

我们从 14 名接受莫西沙星静脉注射 ( n  = 8) 或口服 ( n  = 6) 的参与者那里获得了 43 种莫西沙星浓度。体重≤ 40 kg 的参与者的莫西沙星剂量为每天 10 mg/kg，体重 > 40 kg 的参与者的剂量为每天 400 mg。群体均数清除率和均数分布容积分别为 18.2 L/h 和 167 L。口服吸收由一级过程描述。口服生物利用度的估计程度变化很大（范围 20-91%）。总体重被确定为清除率和分布容积的协变量，并大大减少了这两个参数的随机无法解释的个体间变异性。没有参与者出现与莫西沙星相关的疑似严重不良反应。

结论

这些数据补充了现有文献以支持在某些情况下对儿童使用莫西沙星；然而，需要对莫西沙星的安全性和有效性进行进一步的前瞻性研究。