Quantitative evaluation of biliary elimination of gadoxetate, a magnetic resonance imaging contrast agent, via geometrical isomer-specific transporting system in rats
Quantitative evaluation of biliary elimination of gadoxetate, a magnetic resonance imaging contrast agent, via geometrical isomer-specific transporting system in rats
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通过大鼠几何异构体特异性转运系统对磁共振成像造影剂钆塞酯的胆汁消除进行定量评估
DOI：
10.1002/bdd.1907
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发表时间：
2014
影响因子：
2.1
通讯作者：
Ichiro Koshiishi
中科院分区：
文献类型：
--
作者：
Junji Ogawa;Azusa Yokota;Takuya Araki;Tohru Aomori;Tomonori Nakamura;Koujirou Yamamoto;Ichiro Koshiishi
Gadoxetate是一种磁共振成像造影剂，被排入胆汁中。Gadoxetate几何异构体根据离子状态的不同被层析分为两类(Gis-I和Gis-II；65：35w/w)；然而，每种异构体在体内的消除机制仍然存在争议。因此，研究了载体介导的转运系统对加多西他胆汁排泄的贡献。给大鼠静脉注射Gadoxetate，用高效液相色谱法测定Gis-I和Gis-II的血药浓度和胆汁排泄时间。结果表明，34.7%的Gis-I(S)和22.6%的Gadoxetate在注射后30 min内被迅速清除到胆汁中。血浆中残留Gis-I(R)和Gis-II的含量按一级消除过程类似地降低(T1/2= 23-27 )，注射后2 h内64.0%的Gis-I(R)和Gis-II(49.6%)被排泄到胆汁中。Gis-I(R)和Gis-II在大鼠体内的消除半衰期无显著差异。结论：静脉注射后不迟于30 m in，Gadoxetate的几何构象异构体在大鼠体内通过载体转运系统被清除到胆汁中。版权所有©2014 John Wiley&Sons，Ltd.
Gadoxetate, a magnetic resonance imaging contrast agent, is eliminated into bile. Gadoxetate geometrical isomers are chromatographically classified into two groups by differences between their ionic states (GIs‐I and GIs‐II; 65:35 w/w); however, the elimination mechanism of each isomerin vivoremains controversial. Thus, the contribution of carrier‐mediated transport systems on the biliary elimination of gadoxetate was examined. Gadoxetate was injected intravenously into rats, and the time courses of the plasma concentrations and biliary elimination of GIs‐I and GIs‐II were examined by high‐performance liquid chromatography techniques. The results showed that 34.7% of GIs‐I (GIs‐I(s); 22.6% of gadoxetate) was quickly eliminated into bile within 30 min after injection. The contents of the residual GIs‐I (GIs‐I(r)) and GIs‐II in plasma similarly decreased according to a first‐order elimination process (t1/2= 23–27 min), and 64.0% of GIs‐I(r) and GIs‐II (49.6% of gadoxetate) was eliminated into the bile within 2 h after injection. There was no significant difference between the elimination half‐lives of GIs‐I(r) and GIs‐II in rats. In conclusion, the geometrical isomer with specific conformation corresponding to 22.6% of gadoxetate was eliminated into bile in rats via a carrier‐mediated transport system no later than 30 min after intravenous injection. Copyright © 2014 John Wiley & Sons, Ltd.