一个基于生理学的药理动力学模型,用于人类的甲基甲酸
Shiyu Chen1, Zhenzhen Shi2, Qiang Zhang3
1Department of Biostatistics and Bioinformatics, Rollins School of Public Health, Emory University, GA 30322, USA.
一个新的基于人体生理学的药理动力学 (PBPK) 模型预测了二甲基甲酸盐 (DEP) 和其代谢物单甲基甲酸盐 (MEP) 的内部度. 这个模型有助于评估DEP.
科学领域:
- 环境健康 环境健康
- 毒理学 毒理学 毒理学
- 药理动力学 药理动力学
背景情况:
- 甲基甲酸 (DEP) 是一种广泛使用的工业和消费化学品.
- 暴露于DEP与男性生殖,发育和肝脏毒性有关.
- 了解内部DEP和单乙烯甲酸盐 (MEP) 度对于毒性评估至关重要.
研究的目的:
- 开发一种基于人体生理学上的甲甲酸盐 (DEP) 药理动力学 (PBPK) 模型.
- 预测各种组织中DEP及其代谢物单乙烯甲酸 (MEP) 的内部度.
- 为了提高DEP暴露的风险评估.
主要方法:
- 对于DEP和MEP而言,一个由七个部分组成的人类PBPK模型在R.被实施.
- 模型参数在silico中进行预测,并使用人类尿尿MEP数据进行估计.
- 进行了灵敏度分析和贝叶斯马尔科夫链蒙特卡洛 (MCMC) 模拟.
主要成果:
- 该PBPK模型包括血液,肠道,肝脏,脂肪,皮肤,生殖腺和身体其他部分.
- 确定了影响DEP和MEP药理动学的关键参数.
- 皮肤吸收被证实是显著的暴露途径,衣服作为屏障.
结论:
- 开发的人类PBPK模型为DEP风险评估提供了定量工具.
- 该模型有助于理解DEP和MEP内部剂量计.
- 进一步精制可以提高其在监管毒理学中的实用性.
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