Use of In Silico Mechanistic Models to Support Interspecies Extrapolation of Oral Bioavailability and Formulation Optimization: Model Example Using GastroPlus™

Authors: Lukacova V
Conference: USP
Keywords: animal assays, bioavailability, drug behavior, in silico, in vitro, In vitro in vivo extrapolation (IVIVE), in vivo, oral absorption, PBPK model
Software: GastroPlus®
Division: Simulations Plus

Outline

• Introduction to GastroPlus PBPK model
• Physiological considerations for interspecies extrapolation of oral absorption and bioavailability
• Examples:
– Salt selection
– Animal study was used to verify the in silico model prediction
– Formulation development
– Mechanistic model was used to understand the formulation behavior in vivo based on animal study
– in vitro – in vivo dissolution extrapolation
– Animal data was used to validate methodology for in vitro – in vivo dissolution extrapolation
– Interspecies differences
– Mechanistic model was used to investigate interindividual and interspecies differences in formulation behavior
• Summary

USP Workshops Exploring the Science of Drug Absorption, October 15-16, 2018, Rockville, Maryland

By Viera Lukacova