A Physiologically Based Pharmacokinetic Model for Absorption and Distribution of Imatinib in Human Body

Bulletin of the Korean chemical society

Jeong Keun Ahn¹  Mohammad Mahfuz Chowdhury¹  Do Hyun Kim¹ 

关键词: Physiologically based pharmacokinetic model;    Imatinib;    Compartmental absorption and transitmodel;    Plasma concentration profile;   

DOI  :  

学科分类：化学（综合）

来源: Korean Chemical Society

【 摘 要 】

A whole body physiologically based pharmacokinetic (PBPK) model was applied to investigate absorption,distribution, and physiologic variations on pharmacokinetics of imatinib in human body. Previously publishedpharmacokinetic data of the drug after intravenous (i.v.) infusion and oral administration were simulated by thePBPK model. Oral dose absorption kinetics were analyzed by adopting a compartmental absorption and transitmodel in gut section. Tissue/plasma partition coefficients of drug after i.v. infusion were also used for oraladministration. Sensitivity analysis of the PBPK model was carried out by taking parameters that werecommonly subject to variation in human. Drug concentration in adipose tissue was found to be higher thanthose in other tissues, suggesting that adipose tissue plays a role as a storage tissue for the drug. Variations ofmetabolism in liver, body weight, and blood/plasma partition coefficient were found to be important factorsaffecting the plasma concentration profile of drug in human body.

【 授权许可】

Unknown