环孢素、硝苯地平等5种肾移植受者常用药物对人体红细胞硫嘌呤甲基转移酶活性的影响

Effects of five drugs including ciclosporin and nifedipine which were usually used in patients with kidney transplantation on erythrocyte thiopurine methyltransferase activity

目的:研究肾移植受者中常与硫唑嘌呤(AZA)同时服用的药物如环孢素、泼尼松的活性代谢物氢化可的松、硝苯地平、卡托普利以及别嘌呤醇对硫嘌呤甲基转移酶(TPMT)活性的影响。方法:应用高效液相色谱法(HPLC)测定健康受试者红细胞TPMT活性,其中中等活性和正常活性受试者各8例,计算药物各浓度对应的平均TPMT活性抑制率及有抑制作用药物的平均IC_(50)值。结果:环孢素、氢化可的松、卡托普利以及别嘌呤醇对TPMT活性抑制作用较弱。硝苯地平能明显抑制TPMT的活性,中等活性组的平均IC_(50)值为(24±17)μg/mL,正常活性组的平均,IC_(50)值为(12±10)μg/mL。结论:硝苯地平能明显抑制TPMT活性,当硝笨地平与嘌呤类药物同时服用时,应警惕可能发生不良相互作用。

AIM： To investigate the effects of five drugs which were usually used simultaneously with azathioprine （AZA） in patients with kidney transplantation： ciclosporin, hydrocortisone, nifedipine, captopril and allopurinol on erythrocyte thiopurine methyltransferase （TPMT） activity. METHODS： The erythrocyte TPMT activity of healthy volunteers was measured by high-performance liquid chromatography （HPLC）. Sixteen volunteers were chosen, in which 8 cases with intermediate TPMT activity and others with normal TPMT activity. The mean inhibition ratio of each drug concentration and the mean IC50 values of the inhibitors were determined. RESULTS： Ciclosporin, hydrocortisone, captopril and allopurinol had nearly no impacts on TPMT activity. Nifedipine highly inhibited TPMT activity in vitro, the mean IC50 value in intermediate TPMT activity group was （24 ± 17） μg/mL and in normal TPMT activity group was （ 12 ± 10） μg/mL. CONCLUSION： The co-administration of nifedipine and thiopurines may lead to drug interactions.