以形态学为基础的人口药理动力学和生理学基础的药理动力学建模,以优化塞法林手术预防
Shuhan Liu1, Aleksas Matvekas1, Tamara Naimi1
1College of Pharmacy, University of Michigan, Ann Arbor, Michigan, USA.
Pharmacotherapy
|September 20, 2023
概括
功能和身体组成测量,而不仅仅是体重,更好地预测手术地点的塞法林药物水平. 需要进一步的研究来完善剂量策略,以预防肥胖患者感染.
科学领域:
- 药理动力学 药理动力学
- 手术部位感染的预防 手术部位感染的预防
- 肥胖医学 肥胖医学
背景情况:
- 塞法索林是全球预防手术部位感染 (SSI) 的首要抗生素.
- 目前的指导方针建议根据体重进行剂量调整,但忽视了身体成分.
- 形态学提供了一种方法,可以从放射学数据中量化身体成分,以改善剂量.
研究的目的:
- 将体重与形态测量进行比较,以预测塞法林的药理动力学.
- 在接受结直肠手术的肥胖患者中,以告知塞法林剂量分层.
- 开发一种基于形态学的群体药理动力学 (PopPK) 模型.
主要方法:
- 预期研究测量血和组织中塞法林度.
- 开发一种基于形态学的PopPK模型.
- 为患有病态肥胖症的患者构建基于生理学的药理动力学 (PBPK) 模型.
主要成果:
- 从58名患者收集的形态学和药理动力学数据.
- 估计的肌素清除率 (eCLcr) 和L3的体内深度 (体内深度_L3) 被确定为关键共变量.
- 在eCLcr≥105毫升/分钟和身体深度L3≥300毫米的患者中,皮下脂肪度低于目标水平的预测.
结论:
- 形态测量和功能优于体重来预测塞法林暴露.
- 需要对不同人群进行进一步的研究,并就目标暴露达成共识.
- 目前的数据不足以改变塞法林剂量的临床实践.
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