一个基于生理学的动力模型,用于量化人类对DEET的暴露
Min-Soo Kim1, Abdullah Hamadeh1, Jason Kowalski2
1School of Pharmacy, University of Waterloo, 10A Victoria Street South, Kitchener, Ontario, N2G 1C5, Canada.
一个基于N,N-二甲基-3-甲基胺 (DEET) 和其代谢物的药理动力学模型 (PBK) 已开发并在人类中验证. 该模型有助于估计DEET暴露,并评估使用驱虫剂的儿童的安全性.
科学领域:
- 毒理学 毒理学 毒理学
- 药理动力学 药理动力学
- 环境健康 环境健康
背景情况:
- N,N-二甲基-3-甲基胺 (DEET) 是用于对抗蚊子和的昆虫驱虫剂的关键成分.
- 对DEET及其主要代谢物3 - - 甲基基酸 (DCBA) 开发了一种基于人体药理动力学 (PBK) 的模型.
研究的目的:
- 开发和验证人类PBK模型的DEET和DCBA.
- 解释儿童DEET暴露研究中的生物监测数据.
主要方法:
- 对于DEET和DCBA的综合系统和机械皮肤吸收模型.
- 利用体外,体内和体内数据用于模型开发和优化.
- 根据人类药理动力学和生物监测研究数据验证的模型预测.
主要成果:
- 集成的PBK模型准确地预测了尿中DEET度在2倍的范围内.
- 据估计,夏令营中典型的DEET应用量为24小时内69.0毫克,皮肤生物利用率为24.2%.
- 模拟的DEET时间过程概况与已公布的药理动力学数据保持一致.
结论:
- 通过使用集成数据,成功开发了对DEET和DCBA的验证的人类PBK模型.
- 该模型允许估计外部DEET剂量,并证实了超过关注水平的暴露幅度.
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