连续的Nab-Paclitaxel化疗周期对肠道微生物群和药物动力学行为的影响
Xinyue Zhang1, Weiwei Xie1, Yuqian Zhang1
1Department of Clinical Pharmacy, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, P. R. China.
Technology in cancer research & treatment
|March 17, 2026
概括
连续的nab-paclitaxel化疗周期会改变肠道微生物群和药物的药理动力学. 这些变化通过非CYP依赖的途径发生,这表明针对微生物群的干预可以优化癌症治疗.
科学领域:
- 药理学和微生物学 药理学和微生物学
- 癌症化疗 癌症化疗
- 肠道微生物组研究研究
背景情况:
- 纳布-帕克利塔塞尔是一种关键的化疗剂,但其系统性作用,特别是对肠道微生物群的作用,尚未完全理解.
- 肠道微生物群在药物代谢中发挥作用,影响化疗的疗效和毒性.
- 了解重复的nab-paclitaxel循环对宿主微生物群相互作用的影响对于优化治疗至关重要.
研究的目的:
- 为了研究连续的nab-paclitaxel化疗周期对大鼠肠道微生物群组成的影响.
- 评估纳布-帕克利塔塞尔对肠道屏障功能和药代动力学 (PK) 行为的影响.
- 探索潜在的机制,包括CYP酶的作用,在纳布-帕克利塔塞尔改变的PK概况.
主要方法:
- 通过尾静脉注射,大鼠接受了一,两或三次纳布-帕克利塔塞尔循环.
- 用16S rRNA测序分析了肠道微生物组成.
- 血药物度通过LC-MS/MS测量,肝脏CYP3A/CYP2C表达通过西部斑和qPCR进行评估.
主要成果:
- 纳布-帕克利塔塞尔显著改变了肠道微生物群的组成,增加了蛋白质细菌和蓝藻细菌,同时减少了Actinobacteriota和Firmicutes.
- 微生物多样性指数随着重复剂量的增加而增加.
- 药物动力学显示清除减少,AUC和Cmax增加,而肝脏CYP3A1或CYP2C11表达没有显著变化.
结论:
- 连续的nab-paclitaxel循环诱导肠道微生物群失调,并通过非CYP依赖的机制改变药物药理动力学.
- 肠道微生物群 - 肝脏轴极大地影响化疗药物处置.
- 这些发现支持开发针对微生物群的干预措施,以提高化疗的疗效.
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