评估儿科结核病剂量指南:基于模型的个人数据汇总分析
Lufina Tsirizani Galileya1,2, Roeland E Wasmann1, Chishala Chabala1,3,4
1Division of Clinical Pharmacology, Department of Medicine, University of Cape Town, Cape Town, South Africa.
PLoS medicine
|November 21, 2023
概括
儿童结核病药物剂量需要优化. 增加3个月以上儿童的利芬素剂量可以改善暴露和治疗,而艾滋病毒药物相互作用需要进一步研究.
科学领域:
- 药理动力学和药理动力学
- 儿童传染病 儿童传染病
- 结核病治疗方法 结核病治疗方法
背景情况:
- 目前世界卫生组织 (WHO) 的儿科结核病剂量指南导致药物暴露率低于最佳水平.
- 儿科药物动力学研究通常很小,导致结果的变化和不确定性.
- 从大型药理动力学研究中汇集数据对于优化儿科结核病剂量至关重要.
研究的目的:
- 确定影响结核病治疗儿童药物暴露的关键共变量.
- 为儿童群体优化结核病剂量方案.
- 在儿童中描述里法皮辛,异亚和皮拉津胺的药理动力学.
主要方法:
- 利用非线性混合效应建模来分析来自四个国家的387名儿童的药理动力学数据.
- 研究了人类免疫缺陷病毒 (HIV),抗逆转录病毒疗法 (ART),药物配方,年龄和体型对药物药理动学的影响.
- 采用全度测量来测量里芬素,异亚和皮拉津胺的分泌量和分泌量.
主要成果:
- 年龄显著影响了里芬素和异化的生物可用性和清除,儿童在2年后达到成人水平,完全清除成熟时间约为3年.
- 艾滋病毒感染本身并没有改变药理动力学,但抗逆转录病毒疗法 (ART) 显示出显著的相互作用:洛皮纳维尔/里托纳维尔降低了利法素清除率和增加了皮拉津胺清除率,而埃法维伦兹和洛皮纳维尔/里托纳维尔降低了伊索尼亚齐德的生物可用性.
- 模拟表明,当前世卫组织推的剂量导致3个月以上儿童的利法素暴露率降低,这表明需要调整剂量.
结论:
- 超过3个月的儿童比成年人暴露于利法素的水平较低,因此需要增加75-150毫克的剂量以改善治疗.
- 艾滋病毒感染儿童的药物暴露变化可能是由于同时服用ART,而不是艾滋病毒感染本身.
- 进一步评估结核病药物和ART (lopinavir/ritonavir,efavirenz) 之间的药物相互作用对于未来的剂量指导至关重要.
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