在患有肺结核脑膜炎的患者中预测贝达基林中枢神经系统暴露,使用基于生理学的药物动力学建模
Krina Mehta1, Pavel Balazki2, Piet H van der Graaf3,4
1Leiden Academic Centre for Drug Research, Leiden University, Leiden, The Netherlands. krinaj@gmail.com.
贝达奎林是什么意思?贝达奎林是什么意思?
科学领域:
- 药理动力学和药物新陈代谢
- 神经科学和神经病学 神经科学和神经病学
- 传染病与微生物学
背景情况:
- 结核性脑膜炎 (TBM) 中药物耐药性的增加需要替代治疗方法.
- 贝达基林是抗药性TBM的潜在候选者.
- 了解贝达基林的中枢神经系统 (CNS) 透对于疗效至关重要.
研究的目的:
- 开发一种基于生理学的药理动力学 (PBPK) 模型,用于贝达基林.
- 预测贝达基林及其代谢物M2在中枢神经系统中的暴露.
- 为了比较中枢神经系统暴露与肺和血暴露.
主要方法:
- 开发了一种整体PBPK模型,其中包括大脑和脑脊液 (CSF) 分区.
- 根据患者血和CSF的药理动力学数据验证了模型.
- 在临床剂量方案中模拟中枢神经系统和肺部暴露.
主要成果:
- 该PBPK模型准确地预测了血和脑脊液中的贝达基林和M2度.
- 组织结合显著影响中枢神经系统中的贝达基林度.
- 预测的未结合的细胞内大脑度比血和肺部要低得多 (7%).
结论:
- 预计贝达奎林的未结合的大脑度将低于肺部度.
- 这表明,与肺结核相比,贝达基林对抗药性TBM的疗效可能较低.
- 需要进一步的研究来优化贝达奎林在中枢神经系统感染中的剂量.
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