在患有腹腔炎的患者中,使用生理学基础的药理动力学方法评估万科米辛进入脑脊液的透率
Larissa Martins Alves Guimarães1, Letícia Oliveira de Vasconcellos Nacif1, Jhohann Richard de Lima Benzi2
1Laboratory of Pharmacometrics (LabFarma), Faculty of Pharmacy, Federal University of Rio de Janeiro, Rio de Janeiro, 21941-902, Brazil.
Pharmaceutical research
|February 4, 2026
概括
一个新的生理学基础的药理动力学 (PBPK) 模型显示,万科米辛的透率低且可变的中枢神经系统 (CNS). 这凸显了对心室炎患者治疗药物监测的需要.
科学领域:
- 药理动力学和药理动力学
- 传染性疾病 传染性疾病
- 计算生物学 计算生物学
背景情况:
- 范科米辛对于治疗格拉姆阳性细菌中枢神经系统 (CNS) 感染至关重要.
- 直接测量大脑脊髓液 (CSF) 中的万科米辛具有挑战性,需要使用替代评估方法.
- 腹腔炎的治疗需要了解中枢神经系统中药物暴露.
研究的目的:
- 开发一种基于生理学的药理动力学 (PBPK) 模型,用于血和脑液中的万科米辛.
- 在患有腹腔炎的患者中表征范科米辛暴露.
- 为优化中枢神经系统感染中的万科米辛剂量提供一种工具.
主要方法:
- 使用PK-Sim®进行生理学基础的药理动力学 (PBPK) 建模和仿真.
- 将万科米辛的物理化学参数纳入大分子模型.
- 使用罗杰斯-罗兰模型进行组织分布,并调整CSF-to-plasma分区系数.
主要成果:
- 该PBPK模型纳入了万科米辛的低脑透性 (CSF-to-plasma 分割系数为0.17).
- 模型验证使用了33名腹腔炎患者的数据.
- 模拟的平均万科米辛度在血中为32 mg/L,在脑脊液中为7.2 mg/L,预测的脑脊液/血比为0.22.
结论:
- 范科米辛在中枢神经系统中透率低且可变.
- 治疗药物监测和个性化剂量对心室炎患者至关重要.
- PBPK模型可以帮助选择最佳的剂量方案,并确定中枢神经系统感染的PK/PD关系.
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