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Trantinterol, a Novel beta(2)-Adrenoceptor Agonist, Noncompetitively Inhibits P-Glycoprotein Function in Vitro and in Vivo 期刊论文

编号：

196d3c26-b20d-405c-acce-e738f3bb2d7d
作者：

Wang, Tingting(王婷婷)#^[1,2]Sun, Yantong^[3];Ma, Wenxiao#^[1,5]Yang, Zhichao^[1];Yang, Junfeng^[1];Liu, Jingrui(刘景瑞)^[1]Fan, Hongbo^[3];Yang, Yan(杨艳)*^[1,4]Gu, Jingkai(顾景凯)*^[2,4]Fawcett, John Paul^[6];Guo, Yingjie*^[1]
语种：

英文
期刊：

MOLECULAR PHARMACEUTICS ISSN：1543-8384 2015 年 12 卷 1 期 (1 - 9) ; JAN
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关键词：

P-gp trantinterol noncompetitive inhibitor MDCK-MDR1 cells Caco-2 cells
摘要：

P-glycoprotein (P-gp)-mediated drug-drug interactions are important factors causing adverse effects of drugs in clinical use. The aim of this study was to determine whether trantinterol (also known as SPFF), a novel beta(2)-adrenoceptor agonist, was a P-gp inhibitor or substrate. The results showed that trantinterol was not a substrate of P-gp but increased rhodamine 123 (Rho 123) uptake by MDCK-MDR1 cells and decreased the efflux transport of both Rho 123 and cyclosporine A (CsA) in bidirectional transport studies across MDCK-MDR1 cell monolayers. This suggested that trantinterol was a P-gp inhibitor but not a P-gp substrate. The mechanism of inhibition was investigated in the P-gp-Glo assay system, where it was found that trantinterol inhibited P-gp ATPase activity in a dose-dependent manner. A subsequent study using the antibody binding assay with the conformation-sensitive P-gp-specific antibody UIC2 confirmed that trantinterol decreased UIC2 binding at 10 mu M in contrast to the competitive inhibitor, verapamil. This suggested that trantinterol was a noncompetitive inhibitor of P-gp. Finally, a pharmacokinetic study in rat showed that trantinterol significantly increased the area under the plasma concentration-time curve (AUC) and maximum plasma concentration (C-max) of digoxin and paclitaxel (PAC), and the C-max of cyclosporine A (CsA). In summary, trantinterol is a potent noncompetitive P-gp inhibitor which may increase the bioavailability of other P-gp substrate drugs coadministered with it.
推荐引用方式
GB/T 7714：

Wang Tingting,Sun Yantong,Ma Wenxiao, et al. Trantinterol, a Novel beta(2)-Adrenoceptor Agonist, Noncompetitively Inhibits P-Glycoprotein Function in Vitro and in Vivo [J].MOLECULAR PHARMACEUTICS,2015,12(1):1-9.
APA：

Wang Tingting,Sun Yantong,Ma Wenxiao,Yang Zhichao,&Guo Yingjie.(2015).Trantinterol, a Novel beta(2)-Adrenoceptor Agonist, Noncompetitively Inhibits P-Glycoprotein Function in Vitro and in Vivo .MOLECULAR PHARMACEUTICS,12(1):1-9.
MLA：

Wang Tingting, et al. "Trantinterol, a Novel beta(2)-Adrenoceptor Agonist, Noncompetitively Inhibits P-Glycoprotein Function in Vitro and in Vivo" .MOLECULAR PHARMACEUTICS 12,1(2015):1-9.
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