他克莫司在中国健康人体内的药动学特征

Pharmacokinetic Characteristics of Tacrolimus in Chinese Healthy Volunteers

采用随机开放试验设计,研究了22名中国健康男性志愿者单剂量口服5mg他克莫司胶囊的药动学特征。以环孢素D为内标,建立了LC-MS/MS法测定他克莫司在全血中浓度。主要药动学参数为:T1/2(31.4±9.0)h,cmax(41.3±19.6)ng/ml,Tmax(1.7±0.8)h,AUC0-t(330.3±143.5)h·ng·ml-1,AUC0-∝(394.9±186.3)h·ng·ml-1。所得结果与国外文献接近,他克莫司在人体的吸收代谢存在较大的个体变异,变异来源与CYP3A4/5的基因多态性密切相关。

According to an open-label randomized design, pharmacokinetic characteristics of tacrolimus in twenty-two Chinese healthy male volunteers after a single oral dose of 5 mg tacrolimus were discussed. Concentrations of tacrolimus in whole blood were determined by LC-MS/MS and cyclosporin D was used as intemal standard. The pharmacokinetic parameters were as follows： Tv2 （31.4±9.0） h, Cmax （41.3±19.6） ng/ml, Tmax （1.7±0.8） h, AUC0→t （330.3± 143.5） h.ng.ml-1, AUC0→∞ （394.9±186.3）h.ng.ml-1. The results were approximate to those from foreign literature, and there are great inter-individual variations in the absorption and metabolism of tacrolimus in humans due to the close relation with the gene polymorphism of CYP3A4/5.