生理药动学模型预测阿戈美拉汀口服给药的体内药动学过程

发布时间：2019-03-08 13:42

【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。
[Abstract]:Aim: to establish a physiological pharmacokinetic (PBPK) model of agomeratine in human body and to predict its pharmacokinetic process after oral administration. Methods: the plasma concentrations of agometine in healthy men with different genetic types were determined. The PBPK model of oral administration of Agomelatine was established by Gastro PlusTM software, and the model was optimized and verified. Results: the model fitted the drug-time curves of agometine and compared with the measured values, R2 was 0.95. The absolute bioavailability of agometine was predicted to be 1% ~ 7% after oral administration, and it was widely distributed in human body after oral administration, and the exposure amount of each tissue / organ was the highest in liver, brain and red bone marrow, which was about 2 times as much as that in blood. Food, age and sex can affect the pharmacokinetics of agometine after oral administration. Conclusion: the PBPK model established by this experiment can simulate the pharmacokinetic process of agomeratine in vivo.
【作者单位】：重庆医科大学附属儿童医院药剂科;重庆医科大学附属儿童医院儿童发育疾病研究教育部重点实验室;四川大学华西药学院临床药学研究中心;
【分类号】：R969.1

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