以生理学为基础的药理动力学模型预测婴儿通过母乳接受多克索鲁比辛和帕克利塔塞尔的暴露
David Damoiseaux1, Frédéric Amant2,3, Jos H Beijnen1,4
1Department of Pharmacy and Pharmacology, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
婴儿通过母乳接触化疗是令人担忧的. PBPK模型预测全身暴露低,但可能存在胃肠道问题,这表明监测和丢弃牛奶的策略对于婴儿安全至关重要.
科学领域:
- 药理学 药理学是指药理学的学科.
- 儿科 儿科 儿科
- 毒理学 毒理学 毒理学
背景情况:
- 有限的数据存在于婴儿的安全性和暴露,当母乳养的母亲接受化疗.
- 了解药物分布到母乳和婴儿的药理动力学对于评估潜在的毒性影响至关重要.
研究的目的:
- 预测接受化疗污染母乳的婴儿对帕克利塔塞尔和多克索鲁比辛的全身和局部 (肠道) 暴露.
- 通过基于生理学的药理动力学 (PBPK) 方法评估母乳中化疗对婴儿安全的影响.
- 评估母乳丢弃策略的有效性.
主要方法:
- 扩展全身PBPK模型用于静脉注射帕克利塔塞尔和多克索鲁比辛.
- 包含一个口服吸收组件用于婴儿预测.
- 在最坏的情况下,婴儿血和肠道组织中的模拟药物暴露.
主要成果:
- 婴儿预测的高血度很低 (3.48nM用于帕克利塔塞尔,0.74nM用于多克索鲁比辛).
- 肠道暴露达到更高的度 (帕克利塔塞尔的1.0微米,多克索鲁比辛的140微米).
- 在化疗后3天丢弃母乳,将暴露率降低了90%以上 (帕克利塔塞尔) 和80% (多克索鲁比辛).
结论:
- PBPK模拟表明,母乳化疗期间母乳养婴儿的全身不良事件风险较低.
- 局部胃肠道不良事件是一个潜在的担忧,需要监测.
- 丢弃母乳3天显著减少婴儿暴露于化疗药物.
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