二甲双胍
药代动力学
生物利用度
药理学
化学
内分泌学
内科学
关节炎
类风湿性关节炎
免疫印迹
运输机
尿
有机阳离子转运蛋白
医学
糖尿病
生物化学
基因
作者
Minghao Chen,Guoquan You,Cong Xie,Ruopeng Yang,Wanyu Hu,Zhijie Zheng,Shuwen Liu,Ling Ye
标识
DOI:10.1016/j.bcp.2021.114413
摘要
Due to the elevated presence of cytokines, the expressions of metabolic enzymes and drug transporters are altered in rheumatoid arthritis (RA). Given the high incidence of diabetes in patients with RA, the aim of the present study was to investigate the metformin pharmacokinetics of a single oral dose in rats with collagen-induced arthritis (CIA). Blood and urine samples were collected at different timepoints, and analyzed by ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS). Tissue samples were also collected to investigate the expression of metabolic enzymes and drug transporters by quantitative reverse transcription-polymerase chain reaction (RT-qPCR) and western blot. The results indicated that the bioavailability of metformin was markedly decreased in the CIA rats. Moreover, metformin was not metabolized by enzymes of rat liver microsomes, suggesting that the decreased bioavailability of metformin was independent of the liver metabolism. In addition, the mRNA, protein expression level and activity of the renal organic cation transporter 2 (OCT2) was markedly increased, suggesting that the enhanced renal clearance of metformin in CIA rats may be due to the up-regulated activity of OCT2. In conclusion, our study suggested that the reduced bioavailability of metformin in CIA rats is possibly related to the up-regulated function of the renal protein OCT2.
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