肠道微生物组通过对ABCB1的转录调节来调节塔克罗利斯的药理动力学
Alexandra L Degraeve1,2, Vincent Haufroid3,4, Axelle Loriot5
1Department of Integrated PharmacoMetrics, PharmacoGenomics and PharmacoKinetics, Louvain Drug Research Institute, Université catholique de Louvain, Brussels, Belgium.
Microbiome
|July 5, 2023
概括
肠道微生物群通过改变ABCB1转运体表达来影响塔克罗利 (TAC) 的药理动力学. 调节肠道细菌可能有助于预测和管理移植患者的TAC剂量变化.
科学领域:
- 药理学 药理学是指药理学的学科.
- 微生物学 微生物学
- 免疫学 免疫学 免疫学
背景情况:
- 塔克罗利 (TAC) 对于移植后的免疫抑制至关重要,但具有显著的药理动力学变异性.
- 肠道微生物群在药物代谢中的作用是一个新兴领域,可能解释TAC的变化.
研究的目的:
- 研究TAC对肠道微生物群组成的影响.
- 确定肠道微生物群对TAC药理动力学 (PK) 的贡献.
主要方法:
- 在体内小鼠模型与TAC的管理和抗生素治疗.
- 无细菌小鼠常规化和体外研究.
- 对ABCB1载体表达和转录因子 (如CAR) 的分析.
主要成果:
- TAC改变了肠道微生物群的组成,并减少了微生物负载.
- 减少微生物负载减少了TAC血液暴露和变异性,与增加的ABCB1表达相关.
- 肠道微生物群通过细菌代谢物和CAR降低肠道ABCB1的表达,影响TAC PK.
结论:
- 肠道微生物群通过细菌代谢物对ABCB1表达的调节会影响TAC血液水平和PK变异性.
- 这些发现对预测药物剂量和管理ABCB1-运输药物的变异性具有临床意义.
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