硫唑嘌呤对环孢素A家兔药动学的影响

目的:研究硫唑嘌呤(azathioprine,AZP)对环孢素A(cyclosporine CSA)血药浓度及药动学的影响。方法:8只家兔灌胃法给CSA口服液(1 5 mg/kg)后,高效液相色谱法(HPLC)测定CSA的血药浓度,恢复1 wk后,灌胃法给AZP(2 0 mg/kg·d)共5 d,并于第5 d灌胃给AZP后再以同样方式给CSA,HPLC测定CSA的血药浓度,以3 P97药动学程序拟合药动学参数。结果:正常家兔合用AZP后,CSA的Cmax、Ke、Ka升高(P <0 .0 5 ) ,T peak、AUC、t1 /2 (Ka)、t1 /2 (ke)降低(P <0 .0 5 ) ,合用AZP前后CSA的CL,V没有变化,其他药动学参数变化差异无显著性。结论:合用AZP前后家兔体内代谢均符合一室模型规律,并且合用AZP后可能加强CSA的作用,减少体内药物的残留量。

THE INFLUENCE OF AZATHIOPRINE ON THE PHARMACOKINETICS OF CYCLOSPORINE A IN RABBITS

Objective: To study the influences of azathioprine (AZP) on cyclosporine A (CSA) serum concentration and pharmacokinetics in rabbits. Methods: Eight rabbits were first administered with CSA (15mg/kg). The serum concentration of CSA at different time was determined by high performance liquid chromatography (HPLC) after administration. One week later, they were administered with AZP continually for five days (20 mg/kg, daily). On the fifth day, CSA was additionally administered after administration of AZP. CSA was determined in the same methods. The pharmacokinetics parameters were calculated with 3P97 program. Results: After administration of AZP, Cmax, Ke and Ka of normal rabbits increased($P$<0.05), T peak, AUC, t1/2(Ka) and t1/2(ke) reduced ($P$<0.05). There was no significant difference in the CL and V of CSA before and after administration of AZP. Also there was no significant difference for other parameters. Conclusion: Before and after oral administration of AZP, metabolism of rabbits in vivo fit to one room model. After administration of AZP, the effect of CSA may be enhanced, and the residual decreased in the body.;