在肥胖和瘦老鼠中基于生理学模型的Cefoxitin,Cefazolin和Piperacillin药理动力学
Yi-Hua Sheng1,2, Katarzyna Kosicka-Noworzyń1,3, Anna Siemiątkowska1,3
1Department of Pharmaceutics, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, 160 Frelinghuysen Road, Piscataway, NJ, 08854, USA.
肥胖会影响药物的药理动力学. 根据肥胖老鼠的总体体重给药抗生素,如皮佩拉西林,塞法索林和塞福西丁,可达到与瘦老鼠相似的药物暴露,支持基于体重的剂量策略.
科学领域:
- 药理学和毒理学 药理学和毒理学
- 肥胖问题研究研究
- 药物代谢和药理动力学
背景情况:
- 全球肥胖率的上升造成了药物药理动力学和肥胖人口最佳剂量的知识差距.
- 了解肥胖如何影响药物分配对于有效的治疗策略至关重要.
研究的目的:
- 为了研究与瘦肉对照相比,在饮食诱导的肥胖大鼠中,皮佩拉西林,塞法索林和塞福西丁的血药理学和组织处置.
- 开发和验证这些抗生素的全身生理学基础的药理动力学 (PBPK) 模型,用于瘦和肥胖的老鼠.
主要方法:
- 在23周的时间里,在雄性长埃文斯大鼠中,饮食诱导的肥胖模型.
- 使用皮佩拉西林,塞法索林和塞福西丁混合物.
- 使用LC-MS/MS分析血和组织度,并开发PBPK模型.
主要成果:
- 大多数血和组织药物度在瘦小鼠和肥胖大鼠之间相似,当用总体体重 (mg/kg) 的剂量时.
- 某些组织在肥胖大鼠中显示药物度始终更高.
- PBPK模型准确地捕捉了药物生物分布,但需要肝脏和脏的队列特定参数.
结论:
- 用总体体重 (mg/kg) 的抗生素剂量是必要的,以实现肥胖老鼠与瘦老鼠相比的药物暴露.
- PBPK模型表明,在肥胖人群中预测药物倾向的潜力.
- 未来的研究可以将这些模型扩展到人类,使用跨物种缩放来改善肥胖患者的抗生素剂量.
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