在中国慢性髓性白血病患者中对达沙替尼的人口药理动力学和药理遗传学分析
Shiyu He1,2, Jinxia Zhao1,2, Jialu Bian1,2
1Department of Pharmacy, Peking University People's Hospital, No. 11 Xizhimen South StreetXicheng District, Beijing, 100044, China.
Pharmaceutical research
|September 19, 2023
概括
这项研究在中国慢性髓性白血病 (CML) 患者中开发了达沙替尼的种群药动力学模型. 年龄显著影响达沙提尼布的暴露,建议对老年患者进行剂量调整.
科学领域:
- 药理动力学和药理动力学
- 在瘤学瘤学.
- 药物基因组学 药物基因组学
背景情况:
- 达沙替尼是一种氨酸激酶抑制剂,是费城染色体阳性慢性髓性白血病 (CML) 的一线治疗方法.
- 达沙替尼的高药理动力学 (PK) 变异性需要个性化的剂量策略.
- 对于中国的CML患者群体中达沙替尼的PK数据有限.
研究的目的:
- 在中国的CML患者中开发达沙替尼的种群药动力学 (PPK) 模型.
- 为了确定影响达沙替尼的个人PK变异性的共变量.
- 优化达沙提尼布剂量,以改善中国患者的治疗结果.
主要方法:
- 使用非线性混合效应 (NLME) 分析进行人口药理动力学建模.
- 分析了来自140名CML患者的754个血度.
- 评估遗传和物理化学参数作为共变量,包括内部和外部验证.
主要成果:
- 一个两部分的模型有效地描述了达沙替尼PK.
- 年龄被确定为影响达沙提尼布清除 (CL/F) 的重要共变量.
- 模拟表明老年患者的药物暴露率更高,没有发现遗传因素是显著的共变量.
结论:
- 对中国CML患者来说,较低的达沙替尼开始剂量可能是合适的.
- 随着年龄的增长,建议减少达沙替尼的剂量,特别是对于老年人.
- 开发的PPK模型有助于为中国患者提供个性化的达沙替尼布.
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