(A) physiologically based pharmacokinetic model for absorption and distribution of imatinib mesylate in a human body

Abstract

A whole body physiologically based pharmacokinetic model is applied to investigate absorption and distribution and the impact of physiologic conditions variation on pharmacokinetic of imatinib mesylate. The model has simulated previously published pharmacokinetic data of the drug in case of intravenous (i.v.) dose and oral dose. Oral dose absorption kinetics has been modeled by adopting Advanced Compartmental Absorption and Transit (ACAT) model in gut section. Tissue:plasma partition coefficients of drug in i.v. dose case are also used in oral dose case. Sensitivity analysis of the whole body PBPK model is done by taking parameters that are commonly subject to variation among human. Adipose tissue drug concentration has been found high compared to other tissues concentration and it act as storage organ for the drug. Variation in metabolism in liver, body weight, and blood:plasma partition coefficient are found to be important factors affecting plasma concentration profile in human body.