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含有达沙替尼无水酸的口服配方改善了人类的可变性和生物可用性
Jiří Hofmann1, Aleš Bartůněk2, Tomáš Hauser1
1Zentiva, k.s., Prague, Czech Republic.
Leukemia
|October 3, 2023
概括
与慢性骨髓性白血病治疗的单酸形式相比,一种新的达沙替尼无水化合物配方显示出更好的吸收和降低的药物动力学变异性. 这一发展可能会导致更好的患者结果.
科学领域:
- 药理学 药理学是指药理学的学科.
- 药物开发 药物开发
背景情况:
- 用于慢性髓性白血病 (CML) 的达沙替尼单水,表现出依赖pH的溶解度.
- 质子抑制剂 (PPI) 经常与达沙替尼 (dasatinib) 联合处方,尽管有警告,这突出了配方方面的挑战.
研究的目的:
- 开发一种具有改善吸收和降低药物动力学变异性的新型达沙替尼无水化合物配方.
- 为了比较新配方与达沙替尼单酸的生物利用性和药物相互作用概况.
主要方法:
- 一项生物可用性研究比较了达沙替尼无水 (110.6毫克) 和单水 (140毫克) 配方.
- 一项药物相互作用研究评估了奥梅普拉对达沙替尼暴露的影响.
- 联合处方分析检查了与PPI一起使用dasatinib的情况.
主要成果:
- 这两种配方均在标准范围内达到Cmax和AUC.
- 达沙替尼无水化合物配方显示AUC0-inf.的体内变化约为3倍,体内变化约为1.5倍,体内变化约为1.5倍.
- 奥梅普拉降低了达沙替尼的AUC0-inf19%,这是临床上无关紧要的下降,并且低于单酸形式所观察到的.
结论:
- 新的达沙替尼无水化合物配方比单水化合物形式提供了更好的吸收和药物动力学稳定性.
- 这些改进可能转化为更强的临床疗效,在临床试验中需要进一步调查.
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