瑞格列奈对吡格列酮及其主要活性代谢物在健康人体的药代动力学影响

Effect of repaglinide on the pharmacokinetics of pioglitazone and its active metabolites in healthy volunteers

目的研究瑞格列奈(短效促胰岛素释放剂)对吡格列酮(胰岛素增敏剂)及其主要活性代谢物在健康人体中的药代动力学影响。方法采用随机交叉试验设计,将12名男性健康受试者随机分为吡格列酮单药给药组和吡格列酮与瑞格列奈片合并给药组,清洗期为2周。采用HPLC-MS法测定吡格列酮及其代谢产物M-Ⅳ、M-Ⅲ的血药浓度。结果合并瑞格列奈给药后,PIO、M-Ⅳ、M-Ⅲ的AUC0-τ分别为(6.15±2.71),(12.88±5.16),(5.72±3.06)μg.h.mL-1;Cm ax分别为(626.77±208.21),(272.24±153.76),(132.04±78.42)ng·mL-1;tm ax分别为1.0(0.5～3.0),12.0(12.0～72.0),12.0(12.0～15.0)h,与吡格列酮单药给药组相比,均无显著性改变(P>0.05)。吡格列酮单药和吡格列酮与瑞格列奈片合用在健康人体的药代动力学行为相近。结论瑞格列奈对吡格列酮及其主要活性代谢物在健康人体的药代动力学无显著影响。

Objective To investigate effect of repaglinide on the phar- macokinetics of pioglitazone and its active metabolites in healthy volunteers. Methods A randomized cross - over design was used in the study. 12 healthy volunteers were selected as subjects and were divided randomly to single administration group and co - administration group. The wash - out period was 2 weeks. Plasma concentration of pioglitazone and its active metabolites M- Ⅲ and M- IV were determined by HPLC - MS. Results The pharmacokinetic parameters of PIO, M - IV, M - m after co - administering pioglitazone with repaglinide were as follow： AUC0-τ were （ 6.15 ± 2.71）, （12.88±5.16）, （5.72±3.06） μg·h ·mL^-1; C were （626. 77 ±208.21）, （272. 24± 153.76）, （132.04 ±78.42）ng · mL^-1; t were 1.0（0.5 ±3.0）, 12. 0（12. 0 - 72. 0）, 12.0（ 12.0 - 15.0） h. The results showed that, either AUC0-τ, Cmax or t was unchanged between single administration group and co - administration group. Conclusion Repaglinide has no effect on the pharmaeokinetics of pioglitazone and its active metabilites in vivo.