Application of an Accessible Interface for Pharmacokinetic Modeling and In Vitro to In Vivo Extrapolation

• DOI: 10.3389/fphar.2022.864742
• Publication Date: 2022-04-13T06:40:45Z
• Authors: David E. Hines; Shannon Bell; Xiaoqing Chang; Kamel Mansouri; David Allen; Nicole Kleinstreuer
• Keywords: In vitro toxicology

Regulatory toxicology testing has traditionally relied on in vivo methods to inform decision-making. However, scientific, practical, and ethical considerations have led an increased interest the use of vitro silico fill data gaps. While experiments advantage rapid application across large chemical sets, interpretation coming from these non-animal can be challenging due mechanistic nature many assays. In extrapolation (IVIVE) emerged as a computational tool help facilitate this task. Specifically, IVIVE uses physiologically based pharmacokinetic (PBPK) models estimate tissue-level concentrations various dosing parameters. This approach is used administered dose needed achieve bioactivity within body. results useful metrics such margin exposure or prioritize potential chemicals concern, but PBPK extensive requirements. Thus, access input parameters, well technical requirements applying interpreting models, limited routine part testing. As using for regulatory research contexts continues grow, our perspective that support tools modeling will essential facilitating broader acceptance techniques, encouraging most scientifically sound results. We highlight recent developments two open-access accessible via Integrated Chemical Environment (https://ice.ntp.niehs.nih.gov/), demonstrate types insights provide, discuss how analyses may vitro-based decision making.