Division of Pharmaceutical Sciences, School of Pharmacy, University of Missouri-Kansas City, Kansas City, MO, USA.
J Pharm Pharmacol. 2014 Apr;66(4):574-83. doi: 10.1111/jphp.12139. Epub 2013 Sep 1.
This work was aim to determine in vitro interaction of moxifloxacin with monocarboxylate transporter (MCT) using a human retinal pigment epithelium cells (ARPE-19).
In vitro moxifloxacin uptakes were performed at 37°C across ARPE-19 cells. Concentration-dependent uptake of moxifloxacin was performed to delineate moxifloxacin kinetics with MCT. Effects of MCT substrates, MCT inhibitors, pH and metabolic inhibitors on moxifloxacin uptake were conducted to delineate mechanism of moxifloxacin influx via MCT.
Moxifloxacin uptake was found to exhibit saturable kinetics (K(m) = 1.56 ± 0.32 μM and V(max) = 0.58 ± 0.16 μM/min/mg protein). Higher uptake of moxifloxacin was observed at acidic pH. MCT substrates such as salicylic acid, ofloxacin and L-lactic acid significantly inhibited the uptake of moxifloxacin. Furthermore, moxifloxacin uptake was significantly reduced in the presence of metabolic and MCT inhibitors. Overall, this study demonstrated an interaction of moxifloxacin with Na⁺ and H⁺-coupled transporter, most likely MCT1.
Apart from the lipophilicity, we anticipate that lowest vitreal half-life of intravitreal moxifloxacin compared with other fluoroquinolones may be due to its interaction with MCT. This information might be crucial in clinical settings and can be further explored to improve vitreous half-life and therapeutic efficacy of moxifloxacin.
本研究旨在使用人视网膜色素上皮细胞（ARPE-19）确定莫西沙星与单羧酸转运蛋白（MCT）的体外相互作用。
在 37°C 下通过 ARPE-19 细胞进行莫西沙星的体外摄取。进行莫西沙星的浓度依赖性摄取，以描绘 MCT 与莫西沙星的动力学。进行 MCT 底物、MCT 抑制剂、pH 和代谢抑制剂对莫西沙星摄取的影响，以描绘 MCT 摄取的莫西沙星内流机制。
莫西沙星摄取显示出可饱和的动力学（K(m) = 1.56 ± 0.32 μM 和 V(max) = 0.58 ± 0.16 μM/min/mg 蛋白）。在酸性 pH 值下观察到莫西沙星的摄取较高。MCT 底物，如水杨酸、氧氟沙星和 L-乳酸显著抑制莫西沙星的摄取。此外，在存在代谢和 MCT 抑制剂的情况下，莫西沙星的摄取显著减少。总的来说，这项研究表明莫西沙星与 Na⁺和 H⁺偶联转运蛋白，很可能是 MCT1 相互作用。
除了亲脂性之外，我们预计与其他氟喹诺酮类药物相比，玻璃体内莫西沙星的最低玻璃体半衰期较短可能是由于其与 MCT 的相互作用。这些信息在临床环境中可能至关重要，并可以进一步探索以提高莫西沙星的玻璃体半衰期和治疗效果。
