【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。更多还原

【Abstract】 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.更多还原