伊马替尼和塔克罗利斯在老鼠中的药理动力相互作用
Naling Fan1, Teng Guo1, Liying Du1
1Department of Pharmacy, the Fourth Hospital of Hebei Medical University, Hebei Key Laboratory of Clinical Pharmacy, Shijiazhuang, China.
Current drug metabolism
|December 24, 2024
概括
伊马蒂尼布在大鼠中显著增加了塔克罗利斯水平,而塔克罗利斯在多次剂量后降低了伊马蒂尼布度. 这表明在同时服用这些药物时可能存在药物相互作用.
科学领域:
- 药理学 药理学是指药理学的学科.
- 药物新陈代谢 药物新陈代谢
- 药物相互作用 药物相互作用
背景情况:
- 塔克罗利木斯是一种氨酸抑制剂 (CNI),用于慢性髓性白血病 (CML) 和晚期胃肠道侧管瘤 (GIST).
- 伊马替尼和塔克罗利被CYP3A4/5代谢,并通过P-gp运输,这表明潜在的药物相互作用 (DDI).
研究的目的:
- 在大鼠模型中评估伊马蒂尼布和塔克罗利斯之间的药理动力相互作用.
- 评估同时给药对两种药物的度的影响.
主要方法:
- 在14天的时间里,老鼠接受了不同剂量的伊马替尼布和/或塔克罗利斯.
- 全血塔克罗利斯和血伊马替尼布 (包括N-desmethyl imatinib) 度使用超高性能液态染色体质谱法 (UPLC-MS) 来测量.
主要成果:
- 单剂量伊马替尼不显著影响塔克罗利斯的药理动力学,但伊马替尼增加了塔克罗利斯AUC和Cmax.
- 多剂量塔克罗利斯显著降低了伊马替尼和N-脱甲基伊马替尼AUC和Cmax.
- 伊马替尼在多次剂量后显著增加了塔克罗利斯AUC0-24和AUC0-∞.
结论:
- 伊马蒂尼布在单次和多次给药后会增加塔克罗利斯的血液度.
- 多次服用后,塔克罗利斯可能会影响伊马替尼布的吸收和新陈代谢,因此在同时服用时需要谨慎使用.
- 临床医生应监测药物相互作用时,同时处方伊马替尼和塔克罗利斯.
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