德费拉西洛克斯和西普罗夫洛克萨:与铁酸铁,药理动力学和药理动力学相互作用的潜在三级复合体形成
Imad I Hamdan1, Ruba T Tarawneh1, Firas Awwadi2
1Department of Pharmaceutical Sciences, The University of Jordan, Amman, Jordan.
这项研究表明,deferasirox (DFX) 和ciprofloxacin (CP) 与铁形成高度稳定的三元复合物. 这种组合疗法比单独使用DFX更有效地降低了老鼠的铁含量.
科学领域:
- 药理学 药理学是指药理学的学科.
- 药用化学 医学化学
- 生物化学 生物化学
背景情况:
- 德菲拉西洛克斯 (DFX) 用于铁过载.
- 与DFX同时服用西普洛素 (CP) 可能会影响DFX的疗效.
- 研究药物相互作用对于患者安全和治疗有效性至关重要.
研究的目的:
- 评估三元合物复合物的形成,其中包括deferasirox (DFX),ciprofloxacin (CP) 和铁铁.
- 为了评估这些复杂物对铁含量和DFX药理动力学 in vivo的影响.
- 确定潜在三元复合体的热力学有利性和平衡常数.
主要方法:
- 一个三元复合体 (DFX-CP-Fe) 的制备和表征.
- 理论化学计算以确定平衡常数.
- 在小鼠体内研究,测量血DFX水平,组织铁含量,并进行组织学评估.
主要成果:
- 形成两个热力学偏好的三元复合体: (DFX:CP:Fe) 具有K = 2x10^7和 (DFX:CP:2Fe) 具有K = 2.0x10^60.
- 与单独使用DFX治疗的老鼠相比,用DFX和CP治疗的老鼠在红细胞中铁含量显著降低 (p=0.012).
- 在组合治疗组中观察到较低的血DFX水平和减少脏中的铁沉积.
结论:
- 形成DFX,CP和铁的三元复合体,其稳定常数异常高.
- 与deferasirox同时服用西普洛素似乎在药理学上有利,尽管降低了DFX的血水平,但增强了铁的减少.
- 这些发现表明,CP在涉及DFX的铁化疗方案中可能具有有益作用.
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