BIOMAT Database Logo BIOMAT Database Logo

Considerations for Improving Metabolism Predictions for In Vitro to In Vivo Extrapolation. 2022

Marjory Moreau, and Pankajini Mallick, and Marci Smeltz, and Saad Haider, and Chantel I Nicolas, and Salil N Pendse, and Jeremy A Leonard, and Matthew W Linakis, and Patrick D McMullen, and Rebecca A Clewell, and Harvey J Clewell, and Miyoung Yoon
ScitoVation, LLC, Durham, NC, United States.

High-throughput (HT) in vitro to in vivo extrapolation (IVIVE) is an integral component in new approach method (NAM)-based risk assessment paradigms, for rapidly translating in vitro toxicity assay results into the context of in vivo exposure. When coupled with rapid exposure predictions, HT-IVIVE supports the use of HT in vitro assays for risk-based chemical prioritization. However, the reliability of prioritization based on HT bioactivity data and HT-IVIVE can be limited as the domain of applicability of current HT-IVIVE is generally restricted to intrinsic clearance measured primarily in pharmaceutical compounds. Further, current approaches only consider parent chemical toxicity. These limitations occur because current state-of-the-art HT prediction tools for clearance and metabolite kinetics do not provide reliable data to support HT-IVIVE. This paper discusses current challenges in implementation of IVIVE for prioritization and risk assessment and recommends a path forward for addressing the most pressing needs and expanding the utility of IVIVE.

UI MeSH Term Description Entries

Related Publications

Marjory Moreau, and Pankajini Mallick, and Marci Smeltz, and Saad Haider, and Chantel I Nicolas, and Salil N Pendse, and Jeremy A Leonard, and Matthew W Linakis, and Patrick D McMullen, and Rebecca A Clewell, and Harvey J Clewell, and Miyoung Yoon
In vitro to in vivo extrapolation for trichloroethylene metabolism in humans.
October 1998, Toxicology and applied pharmacology,
Marjory Moreau, and Pankajini Mallick, and Marci Smeltz, and Saad Haider, and Chantel I Nicolas, and Salil N Pendse, and Jeremy A Leonard, and Matthew W Linakis, and Patrick D McMullen, and Rebecca A Clewell, and Harvey J Clewell, and Miyoung Yoon
In vitro-in vivo extrapolation of drug-induced proarrhythmia predictions at the population level.
March 2014, Drug discovery today,
Marjory Moreau, and Pankajini Mallick, and Marci Smeltz, and Saad Haider, and Chantel I Nicolas, and Salil N Pendse, and Jeremy A Leonard, and Matthew W Linakis, and Patrick D McMullen, and Rebecca A Clewell, and Harvey J Clewell, and Miyoung Yoon
In Vitro- in Vivo Extrapolation of Hepatic Metabolism for Different Scenarios - a Toolbox.
November 2018, Chemical research in toxicology,
Marjory Moreau, and Pankajini Mallick, and Marci Smeltz, and Saad Haider, and Chantel I Nicolas, and Salil N Pendse, and Jeremy A Leonard, and Matthew W Linakis, and Patrick D McMullen, and Rebecca A Clewell, and Harvey J Clewell, and Miyoung Yoon
High-throughput PBTK models for in vitro to in vivo extrapolation.
August 2021, Expert opinion on drug metabolism & toxicology,
Marjory Moreau, and Pankajini Mallick, and Marci Smeltz, and Saad Haider, and Chantel I Nicolas, and Salil N Pendse, and Jeremy A Leonard, and Matthew W Linakis, and Patrick D McMullen, and Rebecca A Clewell, and Harvey J Clewell, and Miyoung Yoon
Hepatic Clearance Predictions from In Vitro-In Vivo Extrapolation and the Biopharmaceutics Drug Disposition Classification System.
November 2016, Drug metabolism and disposition: the biological fate of chemicals,
Marjory Moreau, and Pankajini Mallick, and Marci Smeltz, and Saad Haider, and Chantel I Nicolas, and Salil N Pendse, and Jeremy A Leonard, and Matthew W Linakis, and Patrick D McMullen, and Rebecca A Clewell, and Harvey J Clewell, and Miyoung Yoon
A Computational Workflow for Probabilistic Quantitative in Vitro to in Vivo Extrapolation.
January 2018, Frontiers in pharmacology,
Marjory Moreau, and Pankajini Mallick, and Marci Smeltz, and Saad Haider, and Chantel I Nicolas, and Salil N Pendse, and Jeremy A Leonard, and Matthew W Linakis, and Patrick D McMullen, and Rebecca A Clewell, and Harvey J Clewell, and Miyoung Yoon
Key to Opening Kidney for In Vitro-In Vivo Extrapolation Entrance in Health and Disease: Part II: Mechanistic Models and In Vitro-In Vivo Extrapolation.
September 2016, The AAPS journal,
Marjory Moreau, and Pankajini Mallick, and Marci Smeltz, and Saad Haider, and Chantel I Nicolas, and Salil N Pendse, and Jeremy A Leonard, and Matthew W Linakis, and Patrick D McMullen, and Rebecca A Clewell, and Harvey J Clewell, and Miyoung Yoon
A Model Mechanism-Based Explanation of an In Vitro-In Vivo Disconnect for Improving Extrapolation and Translation.
April 2018, The Journal of pharmacology and experimental therapeutics,
Marjory Moreau, and Pankajini Mallick, and Marci Smeltz, and Saad Haider, and Chantel I Nicolas, and Salil N Pendse, and Jeremy A Leonard, and Matthew W Linakis, and Patrick D McMullen, and Rebecca A Clewell, and Harvey J Clewell, and Miyoung Yoon
Quantitative in vitro to in vivo extrapolation of tissues toxicity.
December 2015, Toxicology in vitro : an international journal published in association with BIBRA,
Marjory Moreau, and Pankajini Mallick, and Marci Smeltz, and Saad Haider, and Chantel I Nicolas, and Salil N Pendse, and Jeremy A Leonard, and Matthew W Linakis, and Patrick D McMullen, and Rebecca A Clewell, and Harvey J Clewell, and Miyoung Yoon
Improving in vitro to in vivo extrapolation by incorporating toxicokinetic measurements: a case study of lindane-induced neurotoxicity.
February 2015, Toxicology and applied pharmacology,
Copied contents to your clipboard!