Journal
BIOPHARMACEUTICS & DRUG DISPOSITION
Volume 38, Issue 6, Pages 373-380Publisher
WILEY
DOI: 10.1002/bdd.2075
Keywords
adipose tissue; body weight; fat mobilisation; lipophilic compound; PBPK
Categories
Ask authors/readers for more resources
In a dog toxicokinetic study, an unusual plasma concentration increase of the highly lipophilic compound TAK-357 was observed 2weeks after termination of a 2-week repeated dosing in one dog with acute body weight loss. The present study investigates the cause of this increase. A physiologically based pharmacokinetic (PBPK) model was constructed using the rat and dog pharmacokinetic data. Using the constructed model, the TAK-357 concentration profile in the case of body weight change was simulated. The PBPK model-derived simulation suggested that redistribution from adipose tissues to plasma due to a loss of body fat caused the observed concentration increase of TAK-357 in dog plasma. The analysis demonstrates that the disposition of a highly lipophilic and fat-distributed compound can be affected by acute changes in adipose tissue mass. PBPK modeling and simulation proved to be efficient tools for the quantitative hypothesis testing of apparently atypical PK phenomena resulting from acute physiological changes.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available