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目的 研究合用环孢素（Ｃｙｓ）前后硫唑嘌呤（ＡＺＰ）血药浓度及药物动力学变化。方法 ９只家兔灌胃法给硫唑嘌呤（２０ｍｇ·ｋｇ－１）后，高效液相色谱法（ＨＰＬＣ）测定ＡＺＰ和其主要代谢物６巯基嘌呤（６ＭＰ）的血药浓度，１ｗｋ后，灌胃给Ｃｙｓ（１５ｍｇ·ｋｇ－１，ｑｄ）共４ｄ，并于ｄ４灌胃给Ｃｙｓ后ｌｈ再以同样方式给ＡＺＰ，同法测定ＡＺＰ和６ＭＰ血药浓度，以３Ｐ８７药物动力学程序拟合药物动力学参数。结果 正常家兔合用环孢素后，６ＭＰ的Ｖｃ升高，由合用前（１５９－１±２４－２）升至合用后（２６９－９±１１８－０）Ｌ·ｋｇ－１（Ｐ＜０－０５），ＣＬ升高，由（１－６±０－４）升至（３－２±２－０）Ｌ·ｍｉｎ－１·ｋｇ－１（Ｐ＜０－０５），ＡＵＣ降低，由（７７－９７±２６－０２）降至（４７－０１±２２－７０）ｍｉｎ·μｍｏｌ·Ｌ－１（Ｐ＜０－０５）。其他药动学参数变化差异无显著性。结论 合并用药可引起Ｖｃ、ＣＬ升高，ＡＵＣ降低。
Objective To study the changes of plasma concentration and pharmacokinetics of azathioprine (AZP) before and after co-administration of cyclosporine Cys. Methods Nine rabbits were given intragastric administration of azathioprine (20 mg · kg -1) and the plasma concentrations of AZP and its major metabolite 6-mercaptopurine (6MP) were determined by high performance liquid chromatography (HPLC) 1wk, intragastric administration of Cys (15mg · kg-1, qd) a total of 4d, and in d4 after oral administration of Cys lh again in the same way to AZP, the same method for the determination of AZP and 6MP blood concentration, 3P87 drug Kinetic procedures fit pharmacokinetic parameters. Results In normal rabbits, the Vc of 6MP increased after combined use of cyclosporine (159-1 ± 24-2) and increased to (269-9 ± 118-0) L · kg-1 (P (P <0-05), CL increased from (1-6 ± 0-4) to (3-2 ± 2-0) L · min-1 · kg-1 , From (77-97 ± 26-02) to (47-01 ± 22-70) min · μmol·L-1 (P <0-05). There was no significant difference in other pharmacokinetic parameters. Conclusions Combination of drugs can cause Vc, CL increased, AUC decreased.