基于多药耐药相关蛋白2(Abcc2/Mrp2)在大鼠肾脏表达性别差异的氧氟沙星药动学变化(英文)  

Pharmacokinetic variation of ofloxacin based on gender-related difference in the expression of multidrug resistance-associated protein (Abcc2/Mrp2) in rat kidney

作　　者：王丹[1,2] 魏玉辉[1] 周燕[1] 张国强[1,2] 张帆[1,2] 李育卿[1,2] 张建萍[1,2] 武新安[1] 

机构地区：[1]兰州大学第一医院药剂科,甘肃兰州730000 [2]兰州大学药学院,甘肃兰州730000

出　　处：《药学学报》2012年第5期624-629,共6页Acta Pharmaceutica Sinica

摘　　要：本研究旨在探讨基于多药耐药相关蛋白2(Abcc2/Mrp2)在大鼠肾脏表达性别差异的氧氟沙星的药代动力学变化。采用高效液相色谱法(HPLC)分别测定经尾静脉注射给予氧氟沙星(30 mg.kg1)后大鼠血浆和尿液中氧氟沙星的浓度;通过免疫组化法和流式细胞术分别对雄性和雌性大鼠肾脏Mrp2的表达进行定性和定量分析。结果表明在雄性大鼠体内,氧氟沙星药时曲线下面积(AUC)明显小于雌性大鼠,而尿排总量明显大于雌性大鼠;Mrp2在雄性大鼠肾脏中的表达显著高于雌性大鼠。因此,氧氟沙星药动学性别差异可能是由Mrp2在雄性和雌性大鼠肾脏中的表达差异所引起的。The present study aimed to investigate the pharmacokinetic variation of ofloxacin based on gender-related difference in the expression of multidrug resistance-associated protein（Abcc2/Mrp2） in rat kidney.The concentrations of ofloxacin in rat plasma and urine were determined after tail vein administration（30 mg.kg？1） by high-performance liquid chromatography（HPLC） method.Expression of Mrp2 in kidney of male and female rats was qualitatively and quantitatively detected by immunohistochemistry and flow cytometry,separately.The results showed that AUC value of ofloxacin was lower in male rats than that in female rats and the total amount of ofloxacin excreted in the urine was higher in male rats than that in female rats.And the expression of Mrp2 in male rat kidney was higher than that in female rats.All results suggested that gender-related differences in pharmacokinetics of ofloxacin may be attributed to the differences in the expression of Mrp2 in kidney of male and female rats.

关 键 词：氧氟沙星 多药耐药相关蛋白2 药动学 

分 类 号：R969[医药卫生—药理学]