在糖尿病患者中对二线结核病药物的种群药理学和剂量评估
1Department of Epidemiology, School of Public Health and Key Laboratory of Public Health Safety, Fudan University, Shanghai, China.
概括
在中国糖尿病患者中,五种MDR-TB药物的群体药理学表明,目前的贝达基林剂量可能不足以应对某些耐药水平,这表明可能需要调整剂量.
科学领域:
- 药理动力学 药理动力学
- 传染性疾病 传染性疾病
- 内分泌学 在内分泌学.
背景情况:
- 多药耐药结核病 (MDR-TB) 的治疗需要仔细考虑药物药理动力学 (PK).
- 由于药物代谢发生变化,II型糖尿病患者在MDR-TB治疗中存在独特的挑战.
- 评估当前药物剂量与人口PK的对比对于优化治疗结果至关重要.
研究的目的:
- 评估五种关键的MDR-TB药物的群体药理学 (PK):贝达基林 (BDQ),克洛法齐明 (Clofazimine),赛克洛塞林 (Cycloserine),线索利德 (Linezolid) (LZD) 和莫西素 (MFX).
- 评估目前推的剂量对中国患者的疗效,这些患者同时感染了MDR-TB和II型DM.
- 通过人口PK模型和蒙特卡洛模拟来确定这些药物的目标实现概率 (PTA).
主要方法:
- 从2016年到2019年,在中国进行了一项前性的多中心PK研究.
- 人口PK模型是使用58名参与者的1450个血样本的非线性混合效应分析来开发的.
- 蒙特卡洛模拟用于估计各种药物敏感和耐药的Mycobacterium结核病分离物的PTA.
主要成果:
- 世界卫生组织推的LZD (每天600毫克) 和MFX (每天400毫克) 治疗方案显示,针对M.结核病分离物的PTA>90%,最小抑制度 (MIC) 分别低于0.50毫克/升和0.25毫克/升.
- 目前的BDQ疗法 (每天400毫克2周,然后每周三次200毫克) 对于MIC为0.06毫克/升或更高的隔离物可能无法达到>90%的PTA.
- 在这个特定的患者队列中,成功建立了BDQ,克洛法齐明,环素,LZD和MFX的群体PK模型.
结论:
- 已建立的人口PK模型为优化中国DM患者的MDR-TB治疗提供了基础.
- 目前用于linezolid和moxifloxacin的剂量策略似乎足够适用于敏感隔离物,但贝达基林可能需要剂量调整.
- 基于模型的评估强调了考虑对具有边界耐药水平的分离物进行剂量调整的必要性,以确保治疗疗效.
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