在怀孕期间应用基于生理学的药理动力学方法来预测诺福维尔的药理动力学
Khaled Abduljalil1, Mailys De Sousa Mendes2, Farzaneh Salem2,3
1Certara Predictive Technologies, Sheffield, UK. Khaled.Abduljalil@certara.com.
基于生理学上的药理动力学 (PBPK) 建模准确地预测了孕妇暴露于tenofovir的情况. 这种方法有助于评估胎儿在怀孕期间的药物暴露和风险.
科学领域:
- 药理动力学 药理动力学
- 生理学基础的药理动力学 (PBPK) 建模
- 生殖毒理学 生殖毒理学
背景情况:
- 怀孕期间的孕产妇药物治疗需要了解影响药物暴露的生理变化.
- 基于生理学的药理动力学 (PBPK) 建模提供了对孕产妇和胎儿药物暴露的预测方法.
研究的目的:
- 开发和验证诺福维尔的PBPK模型,以预测怀孕期间母亲和胎儿的暴露.
- 评估PBPK模型预测与孕妇观察数据的准确性.
主要方法:
- 编制了非怀孕个体的体外和体内药理动力学 (PK) 数据,以构建和验证特诺福维尔的PBPK模型.
- 将怀孕期间已知的母亲和胎儿生理变化集成到PBPK模型中.
- 在虚拟孕妇群体中模拟了不同妊娠周的tenofovir暴露.
主要成果:
- 该PBPK模型在非怀孕和怀孕的个体中准确预测了tenofovir PK.
- 观察到的药物度落在PBPK模型的第5-95预测间隔内.
- 预测的带对母体诺福维尔暴露率在术后 (0.85) 与临床观察 (0.60-1.00) 保持一致.
结论:
- PBPK建模是预测孕妇暴露于tenofovir的可靠工具.
- 这种方法可以扩展到预测胎儿暴露和评估其他药物和环境毒素的风险.
- PBPK建模支持怀孕期间药物治疗的知情决策.
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