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

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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 published pharmacokinetic data of the drug after intravenous (i.v.) infusion and oral administration were simulated by the PBPK model. Oral dose absorption kinetics were analyzed by adopting a compartmental absorption and transit model in gut section. Tissue/plasma partition coefficients of drug after i.v. infusion were also used for oral administration. Sensitivity analysis of the PBPK model was carried out by taking parameters that were commonly subject to variation in human. Drug concentration in adipose tissue was found to be higher than those in other tissues, suggesting that adipose tissue plays a role as a storage tissue for the drug. Variations of metabolism in liver, body weight, and blood/plasma partition coefficient were found to be important factors affecting the plasma concentration profile of drug in human body.
Publisher
KOREAN CHEMICAL SOC
Issue Date
2011-11
Language
English
Article Type
Article
Keywords

PLASMA PARTITION-COEFFICIENTS; P-GLYCOPROTEIN; PREDICTION; BIOAVAILABILITY; DRUGS; RAT

Citation

BULLETIN OF THE KOREAN CHEMICAL SOCIETY, v.32, no.11, pp.3967 - 3972

ISSN
0253-2964
DOI
10.5012/bkcs.2011.32.11.3967
URI
http://hdl.handle.net/10203/101309
Appears in Collection
CBE-Journal Papers(저널논문)
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