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在小鼠中对ifosfamide的慢性耐受性:证据表明有昼夜节律

Mylene Malek Chennoufi¹, Naceur A Boughattas¹

¹Laboratory of Pharmacology, Faculty of Medicine, University of Monastir, Monastir, Tunisia.

Chronobiology international

|November 10, 2025

概括

伊福斯法米德 (IFO) 毒性在小鼠中显示出显著的昼夜变化. 早晨给药,特别是大约13个HALO (相当于人类早晨),提供了最高的耐受性和生存率.

科学领域:

药理学药理学是指药理学的学科.
时间生物学时间生物学
在瘤学瘤学.

背景情况:

伊福斯法米德 (IFO) 是一种重要的化疗药物,具有显著的毒性.
它的临床应用受到诸如脑病变等副作用的限制.
对于IFO耐受性的时间治疗原则在很大程度上仍未被探索.

研究的目的:

在小鼠模型中研究ifosfamide (IFO) 毒性的昼夜变化.
为了确定最佳的剂量时间,以减少IFO诱导的毒性.

主要方法:

在瑞士阿尔比诺小鼠中确定IFO的中位致命剂量 (LD50).
在六个昼夜剂量时间 (1, 5, 9, 13, 17, 21 HALO) 中评估了生存率,生存时间,体重和直肠温度.
分析了昼夜节律和IFO对它们的影响.

主要成果:

估计IFO的LD50为520毫克/公斤.
在IFO毒性中观察到显著的昼夜变化 (p < 0.0001).
耐受性最高的发生在13个HALO (72%的存活率),最低的发生在9个HALO (22%的存活率). 在1个HALO (64%的存活率) 时发现了次要峰值.
IFO的使用破坏了正常的昼夜节律,特别是在有毒剂量下.

结论:

伊福斯法米德 (IFO) 毒性表现为双模昼夜模式,耐受性峰值在1个HALO和13个HALO.
翻译推断表明,早晨 (大约6点) 给药可能是人类IFO最安全的治疗窗口.
进一步的慢性治疗研究是有必要的,以优化IFO治疗,并最大限度地减少毒性.

关键词:

如果酸胺.慢性治疗是一种慢性疗法.时间耐受性时间耐受性昼夜节律昼夜节律鼠类模型模型氧沙氨酸是一种酸.

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