Journal: Clinical pharmacology and therapeutics

Article Title: Systems Pharmacology Modeling Predicts Delayed Presentation and Species Differences in Bile Acid-Mediated Troglitazone Hepatotoxicity

doi: 10.1038/clpt.2014.158

Figure Lengend Snippet: List of parameters varied in the human and rat SimPops and results of multiple regression analysis in human SimPops administered 600 mg/day troglitazone (TGZ) for 6 months Human and rat population samples incorporating variability in parameters governing bile acid homeostasis (Bile Acid SimPops) have been constructed previously. 20 Four parameters in the Drug PBPK Sub-model and two system-specific parameters also were varied. (See supplementary material for methods and data used for construction of SimPops). In the human SimPops administered 600 mg/day TGZ for 6 months, a multiple regression analysis was performed to identify the most important parameters in TGZ-mediated hepatotoxicity using 16 varied parameters as independent variables and minimum hepatic ATP as the dependent variable. Statistical significance and standardized coefficients were calculated using JMP 10.

Article Snippet: Human (n=331) and rat (n=191) population samples with variability in 10 (human) or 11 (rat) parameters in the BA homeostasis sub-model (Bile Acid SimPops) were constructed previously within DILIsym using the genetic algorithm in MATLAB ; these Bile Acid SimPops are system-specific, and thus the same Bile Acid SimPops are used to simulate hepatotoxic effects of different compounds.

Techniques: Construct, Inhibition