丙磺舒等药物对双环铂肾排泄的影响及其机理  

Effects of probenecid,methotrexate,digoxin and verapamil on the renal excretion of dicycloplatin in rats

作　　者：李秀琴[1] 陈西敬[1] 任伟超[1] 张辉[1] 顾萱[2] 王广基[1] 

机构地区：[1]中国药科大学药物代谢与动力学研究中心 [2]中国药科大学分析测试中心,南京210009

出　　处：《中国药科大学学报》2006年第5期447-449,共3页Journal of China Pharmaceutical University

基　　金：国家自然科学基金资助项目(No.30472060);国家高技术研究发展计划("八六三"计划)资助项目(No.2003AA2Z347A);江苏省药物代谢重点实验室资助项目(No.2001201)~~

摘　　要：目的:比较在大鼠中丙磺舒、甲氨蝶呤、地高辛、维拉帕米等不同药物转运蛋白底物对双环铂肾排泄的影响。方法:采用原子吸收法测定大鼠尿液中铂浓度,计算4 h尿药累积排泄率。结果:合用不同转运蛋白底物后,双环铂在尿中的排泄量均有所降低,双环铂组4 h累积排泄百分率为(70.7±9.8)%,而合用丙磺舒、维拉帕米、地高辛或甲氨蝶呤后其累积排泄百分率分别下降为(28.8±4.1)%、(34.2±10.1)%、(43.6±2.8)%和(47.4±8.5)%,肾组织铂浓度则由(278.8±112.0)μg/g分别降低或升高为(179.6±122.2),(309.5±88.8),(374.4±90.1),(266.0±107.5)μg/g。结论:合用丙磺舒等药物可抑制双环铂的肾排泄速度,双环铂及其代谢物的肾排泄过程中可能有MRP2,OAT或OATP等药物转运蛋白参与。Aim： To compare the effects of the drug transporter substrates such as probenecid, methotrexate, digoxin and verapamil on renal excretion of dicycloplatin in rats. Method： The concentration of dicycloplatin in urine was measured by atom absorption and cumulate excretion amount of dicycloplatin in the initial 4 h period was evaluated. Results： The excretion amount of dicycloplatin in urine decreased after substrates of the drug transporters were coadministrated. In the initial 4 h period, the total urinal excretion percentage of dicycloplatin after iv injection of dicycloplatin were （70.7±9.8）%, but co-injection of dicycloplatin with probeneside, verapamil, digoxin and methotrexate was responsible for the urinal excretion of platin of （28.8± 4.1）%, （34.2±10.1）%, （43.6±2.8）% and （47.4 ± 8.5）%, respectively. Moreover, renal platin concentration changed from （278.8± 112.0） to （179.6±122.2）, （309.5± 88.8）, （374.4±90. 1）, （266.0±107.5）μg/g, respectively. Conclusion： Drug transporter substrates as probeneside and verapamil reduce the renal excretion of platin when they were used in combination with dicycloplatin. P-gp, OAT or OATP may take part in the excretion of platin.

关 键 词：双环铂 肾排泄 药物转运蛋白 药物动力学 原子吸收测定法 

分 类 号：R96[医药卫生—药理学]