用血清药理与代谢学来识别和描述肝脏载体运输 (OATP1B3-P-gp) 功能的内源生物标志物
Yong-Wen Jin1,2, Yan-Rong Ma1, Ming-Kang Zhang3
1Department of Pharmacy, The First Hospital of Lanzhou University, Lanzhou, 730000, China.
Amino acids
|February 6, 2024
概括
青酸 (AzA) 被确定为评估肝脏输送器功能的一种内源生物标志物. 它的血清水平与有机阴离子载体聚1B3 (OATP1B3) 和P-糖蛋白 (P-gp) 活性相关,有助于药物处置预测.
科学领域:
- 药理学和毒理学 药理学和毒理学
- 药物代谢和药理动力学
- 生物标志物发现发现
背景情况:
- 肝脏药物处置受到有机阴离子载体聚1B3 (OATP1B3) 和P-糖蛋白 (P-gp) 等载体的显著影响.
- 目前,评估肝脏OATP1B3-P-gp功能能力的有效方法是有限的.
- 评估载体功能对于预测药物药理动力学至关重要,特别是在肝病状态下.
研究的目的:
- 确定一个合适的内源生物标志物来评估肝脏中OATP1B3和P-gp的联合功能.
- 为了验证azelaic acid (AzA) 作为OATP1B3-P-gp活动的潜在生物标志物的实用性.
主要方法:
- 建立稳定转染的HEK293T细胞系,表达OATP1B3和P-gp.
- 利用血清药理学和代谢学来识别内源基质.
- 研究了大鼠血清AZA水平与输送器功能之间的相关性,包括诱导性肝损伤期间.
主要成果:
- 青酸 (AzA) 被确定为OATP1B3和P-gp的内源基质.
- 血清AZA度与大鼠OATP1B3和P-gp的探针药物有很强的相关性.
- 在5-甲诱导的肝损伤中,OATP1B3和P-gp表达的降低与血清AzA水平的增加相关.
结论:
- 青酸 (AzA) 作为OATP1B3和P-gp的内源基质.
- AzA是评估OATP1B3-P-gp功能的潜在内源生物标志物.
- 这种生物标志物可以帮助预测肝病中的药物处置变化.
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