【摘要】 目的:建立阿戈美拉汀在人体内的生理药动学(PBPK)模型,预测其口服给药后的体内药动学过程。方法:测定不同基因型群体的健康男性空腹口服阿戈美拉汀后的血药浓度,采用Gastro PlusTM软件建立阿戈美拉汀口服给药的PBPK模型,并进行模型的优化和验证。结果:模型拟合阿戈美拉汀的药-时曲线与实测值比较R2均>0.95。预测阿戈美拉汀口服给药后绝对生物利用度为1%~7%;给药后其在人体内广泛分布,各组织/器官的暴露量以肝、脑和红骨髓中为最高,约为血中药物暴露量的2~4倍;食物、年龄、性别均可对阿戈美拉汀口服给药后的药动学过程产生一定的影响。结论:该试验所建立的PBPK模型可较好模拟阿戈美拉汀的体内药动学过程。更多还原

【Abstract】 OBJECTIVE:To establish a physiological pharmacokinetic model for predicting pharmacokinetic profiles of agomelatine in Humans. METHODS:Blood concentrations of agomelatine in healthy male volunteers with different genotypes were determined after oral administration,and then Gastro PlusTMsoftware was used to build and optimize the PBPK models. RESULTS:Compared with the measured valued,the simulated concentration-time curves,R2 were greater than 0.95. The oral absolute bioavailability of agomelatine was predicted to be about 1%-7%,and it was widely distributed in human body after administration,exposure of agomelatine in liver,brain and redmarrow were about 2-4 times of the blood drug exposure,besides,food,age,sex might affect the pharmacokinetic process of agomelatine. CONCLUSIONS:The PBPK model can accurately simulate the pharmacokinetic profile of agomelatine in vivo.更多还原