基于人口药动力学模型的临界病患者的线索利德剂量优化:两中心前性干预研究
Lu Shi1, Ying Zhang2, Lufen Duan1
1Department of Pharmacy, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, No. 26 Daoqian Street, Gusu District, Suzhou, Jiangsu 215002, China.
临床药剂师主导的精确用线索利德剂量显著降低了不良药物反应,包括线索利德诱导的血小板缩症. 这种基于模型的精确剂量 (MIPD) 方法改善了药理动力学/药理动力学目标的实现,并建议功能障碍患者使用.
科学领域:
- 药理学 药理学是指药理学的学科.
- 临床药房 临床药房
- 制药指标 (Pharmacometrics) 是一个指标.
背景情况:
- 利尼佐利德对于治疗由格拉姆阳性细菌引起的感染至关重要.
- 优化linezolid剂量至关重要,以最大限度地提高疗效并最大限度地降低毒性.
- 种群药动力学 (PPK) 模型为个性化剂量策略提供了一个框架.
研究的目的:
- 用PPK模型评估临床药剂师介导的linezolid治疗方案优化的影响.
- 为了比较标准和优化剂量组之间的linezolid诱导的血小板缩 (LIT) 和其他药物不良反应 (ADRs) 的发生率.
- 评估通过优化linezolid疗法实现药理动力学/药理动力学 (PK/PD) 目标的实现情况.
主要方法:
- 建立了追溯控制组 (2020年1月至2021年6月) 和前性干预组 (2021年7月至2022年6月).
- 临床药剂师在干预组中使用了一种已发表的linezolid PPK模型来优化剂量.
- 一个中断的时间序列分析比较了LIT发病率,ADRs,和群体之间的PK/PD目标实现.
主要成果:
- 与对照组 (n=77) 相比,干预组 (n=103) 的LIT (10.7%对23.4%) 和其他ADR (1.0%对7.8%) 的发生率明显较低.
- 基于模型的精确剂量 (MIPD) 导致Cmin和AUC24/MIC值显著降低 (P<0.001).
- 干预组中Cmin和AUC24/MIC的目标实现率明显高于干预组 (分别为49.6%与20.0%和48.1%与25.6%).
结论:
- 临床药剂师的干预有效地减少了与线索利德治疗相关的LIT和其他ADRs.
- 对于linezolid的MIPD显著改善了Cmin和AUC24/MIC目标的实现.
- 在MIPD指导下,建议对患有功能障碍的患者降低线索利德剂量.
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