新型强效免疫抑制剂他克莫司在健康中国人体的药代动力学

Pharmacokinetics of tacrolimus, a novel potent immunsuppressant in healthy Chinese volunteers

目的 研究中国健康人体单次给予新型强效免疫抑制剂他克莫司 (tacrolimus)胶囊后的药代动力学特征 ,为临床制订合理的用药方案提供参考。方法 健康男性志愿者 8名 ,平均年龄 (2 3.5± 3.85 )岁 ,平均体重 (6 5 .6 9± 5 .70 ) kg。单剂量分别口服他克莫司胶囊 0 .1mg/ kg(n=4)和 0 .15 mg/ kg(n=4) ,用药后 0 .2 5、0 .5、0 .75、1、1.5、2、3、4、6、8、12、2 4、30、36和 46 h分别取血 ,采用酶联免疫法 (EL ISA)测定全血血药浓度 ,绘制药物浓度 -时间曲线图 ,3p87药代动力学程序拟合药 -时曲线 ,推导出其药代动力学模型并求出相应的药代动力学参数。结果 他克莫司口服后全血血药浓度 -时间曲线为二室模型 ,口服 0 .1和 0 .15 mg/ kg两种剂量的主要药代动力学参数分别为 :T1 / 2α为 (0 .6 6± 0 .18)和 (0 .6 6± 0 .2 2 ) h;T1 / 2β(33.87± 8.0 1)和 (32 .71±17.73) h;Tmax为 (1.6 3± 0 .48)和 (1.75± 0 .96 ) h;AUC为 (35 6 .9± 34 .82 )和 (5 35 .8± 317.9) ng· h/ ml;CL 为(0 .2 8± 0 .0 2 83)和 (0 .33± 0 .0 18) L/ (h· kg)。结论 口服他克莫司两种剂量 (0 .1和 0 .15 mg/ kg)的 T1 / 2α、T1 / 2β、Tmax、CL和 K a经统计分析 ,无显著性差异 (P>0 .0 5 )。

Objective: To study the pharmacokinetic profiles of tacrolimous in healthy Chinese volunteers. Methods: Eight healthy male volunteers [average age (23.5±3.85) year old, mean weight (65.69± 5.70)kg] were randomly divided into two groups, and received a single dose of tacrolimus capsule 0.1 or 0.15mg/kg respectively. Whole blood samples were determined by enzyme linked immunosorbant assay. Pharmacokinetic parameters were calculated by 3P87 software. Results: The concentration-time curves were fitted to 2-compartment model with 1st order absorption. The main pharmacokinetic parameters were as follows: T 1/2α (0.66±0.18) and (0.66±0.22)h, T 1/2β(33.87±8.01) and (32.71±17.73)h, T max (1.63±0.48) and (1.75± 0.96)h, AUC (356.9±34.82) and (535.8±317.9)ng·h/ml, CL (0.28±0.0283) and (0.33±0.018)L/(h·kg) for doses of 0.1 and 0.15mg/kg, respectively. Conclusion: After statistical analysis, no significant difference was found between the pharmacokinetic parameters [such as T 1/2α, T 1/2β, T max, CL and Ka (P>0.05)] following oral two different doses, but the rate of absorption of tacrolimus and t 1/2β is variable, which was concordant with that of the references.