丙磺舒等药物对大鼠双环铂肾排泄的影响及其机理研究

THE EFFECTS OF PROBENESIDE AND OTHER DRUGS ON THE RENAL EXCRETION OF DICYCLOPLATIN IN RATS

目的比较丙磺舒、甲氨蝶呤、地高辛、维拉帕米等不同药物转运蛋白底物对大鼠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4h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4h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)μg/g、(309.5±88.8)μg/g、(374.4±90.1)μg/g和(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P-gp、OAT或OATP等药物转运蛋白参与。

Objective methotrexate, digoxin and ve compare the effects of different drug transporter substrates such as probeneside, rapamil on the renal excretion of dicycloplatin in rats. Methods The concentration of dicycloplatin in urine was measured by atom absorption method and cumulates excretion extent in the first four hours was evaluated. Results The excretion amount of dicycloplatin in urine decreased after substrates of different drug transporters used. The total excretion percent of dicycloplatin in urine in the first four hours after iv injection were （ 70.7 ±9.8 ） %, （28.8 ±4.1 ） %, （34.2 ± 10.1 ） %, （ 43.6±2.8 ） % and （47.4 ± 8.5 ）% respectively for using dicycloplatin only, and for using dicycloplatin pluss probeneside, verapamil, digoxin and methotrexate, however, the renal plating concentration changed from （278.8 ± 112.0） μg/g to （179.6 ± 122.2）μg/g, （309.5 ± 88.8 ） μg/g, （ 374.4±90.1 ）μg/g and （ 266.0 ± 107.5 ）μg/g respectively. Conclusion Drug transporter substrates as probeneside and verapamil reduce the renal excretion of plating after they were used combine with dicycloplatin. P-gp, OAT or OATP may take part in the excretion processes.