The use of PBPK modelling to evaluate Acibenzolar-S-Methyl exposure in rat and human models and effect of GIT changes on diclofenac PK

Abstract

The use of physiologically based pharmacokinetic (PBPK) modelling has become more popular in the last years. Companies like Certara developed commercial software which is user friendly and easy to use even for scientist with limited programming and biomathematical skills. This research focused on the use of PBPK modelling software Simcyp Animal to assess the pesticide Acibenzolar-S-Methyl tissue distribution and parameters causing variability in rat model. Results showed that acibenzolar accumulated in rat brain and liver, and the compound was highly sensitive to changes in Km, Vmax, and CLR. The human dietary exposure of acibenzolar was also investigated in several populations. Results showed significant increase of acibenzolar concentrations in populations that have reduced renal elimination such as renal failure patients. The last investigation was performed on beagle dog model to explore the impact of GIT physiological changes on diclofenac PK. Results showed that diclofenac concentrations were altered after changing small intestine transit time. This paper highlighted some of the useful application of PBPK modelling such as assessing the exposure to different chemical in animals and humans and simulate real life scenario to support decision making in veterinary practice.