Luo Bingfeng, Wang Rong, Li Wenbin, Yang Tao, Wang Chang, Lu Hui, Zhao Anpeng, Zhang Juanhong, Jia Zhengping
Key Laboratory of the Plateau Environmental Damage Control, Lanzhou General Hospital of Lanzhou Military Command, PLA, Lanzhou 730050, China; School of Pharmacy, Lanzhou university, Lanzhou 730000, China.
Key Laboratory of the Plateau Environmental Damage Control, Lanzhou General Hospital of Lanzhou Military Command, PLA, Lanzhou 730050, China; School of Pharmacy, Lanzhou university, Lanzhou 730000, China.
Biomed Pharmacother. 2017 May;89:1078-1085. doi: 10.1016/j.biopha.2017.02.092. Epub 2017 Mar 11.
This study was to investigate the influence of physiological changes and the expression of MRP2 efflux transporter on the pharmacokinetics of norfloxacin after acute exposure to high altitude 4300m.
The rats were randomly divided into high altitude group and plain group. Blood gas and biochemical analysis showed that the physiological parameters significantly changed at high altitude. The mRNA and protein expression of MRP2 in high altitude group were higher than plain group in rat small intestine and kidney, while was reduced in rat liver. The AUC, K and C of norfloxacin were significantly reduced in high altitude group (p<0.05). However, the MRT, CL, t and Vd were significantly increased (p<0.05).
These results indicate that physiological indicators and expression levels of drug transporters MRP2 are changed in responded to high altitude, to severely affect norfloxacin pharmacokinetics. These changes may provide basis and new ideas to adjust the dosage and administration, so as to promote rational drug use in the high altitude.
本研究旨在探讨急性暴露于4300米高海拔地区后，生理变化及多药耐药相关蛋白2（MRP2）外排转运体的表达对诺氟沙星药代动力学的影响。
将大鼠随机分为高海拔组和平原组。血气和生化分析表明，高海拔地区的生理参数发生了显著变化。高海拔组大鼠小肠和肾脏中MRP2的mRNA和蛋白表达高于平原组，而肝脏中的表达则降低。高海拔组诺氟沙星的曲线下面积（AUC）、消除速率常数（K）和血药浓度（C）显著降低（p<0.05）。然而，平均滞留时间（MRT）、清除率（CL）、达峰时间（t）和分布容积（Vd）显著增加（p<0.05）。
这些结果表明，高海拔地区生理指标和药物转运体MRP2的表达水平发生改变，严重影响诺氟沙星的药代动力学。这些变化可为调整剂量和给药方式提供依据和新思路，以促进高海拔地区合理用药。
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