Integration of Food Animal Residue Avoidance Databank (FARAD) empirical methods for drug withdrawal interval determination with a mechanistic population-based interactive physiologically based pharmacokinetic (iPBPK) modeling platform: example for flunixin meglumine administration

Miao Li, Yi Hsien Cheng, Jason T. Chittenden, Ronald E. Baynes, Lisa A Tell, Jennifer L. Davis, Thomas W. Vickroy, Jim E. Riviere, Zhoumeng Lin

Research output: Contribution to journalArticle

Abstract

Violative chemical residues in animal-derived food products affect food safety globally and have impact on the trade of international agricultural products. The Food Animal Residue Avoidance Databank program has been developing scientific tools to provide appropriate withdrawal interval (WDI) estimations after extralabel drug use in food animals for the past three decades. One of the tools is physiologically based pharmacokinetic (PBPK) modeling, which is a mechanistic-based approach that can be used to predict tissue residues and WDIs. However, PBPK models are complicated and difficult to use by non-modelers. Therefore, a user-friendly PBPK modeling framework is needed to move this field forward. Flunixin was one of the top five violative drug residues identified in the United States from 2010 to 2016. The objective of this study was to establish a web-based user-friendly framework for the development of new PBPK models for drugs administered to food animals. Specifically, a new PBPK model for both cattle and swine after administration of flunixin meglumine was developed. Population analysis using Monte Carlo simulations was incorporated into the model to predict WDIs following extralabel administration of flunixin meglumine. The population PBPK model was converted to a web-based interactive PBPK (iPBPK) framework to facilitate its application. This iPBPK framework serves as a proof-of-concept for further improvements in the future and it can be applied to develop new models for other drugs in other food animal species, thereby facilitating the application of PBPK modeling in WDI estimation and food safety assessment.

Original languageEnglish (US)
JournalArchives of Toxicology
DOIs
StatePublished - Jan 1 2019

Fingerprint

Pharmacokinetics
Animals
Databases
Food
Pharmaceutical Preparations
Population
Food safety
Food Safety
Drug Residues
Agricultural products
flunixin meglumine
Swine
Tissue

Keywords

  • Drug residues
  • Flunixin
  • Food Animal Residue Avoidance Databank (FARAD)
  • Food safety
  • Interactive physiologically based pharmacokinetic (iPBPK) model
  • Withdrawal intervals (WDIs)

ASJC Scopus subject areas

  • Toxicology
  • Health, Toxicology and Mutagenesis

Cite this

@article{baef6215038d487aa9b4bcecfd280a45,
title = "Integration of Food Animal Residue Avoidance Databank (FARAD) empirical methods for drug withdrawal interval determination with a mechanistic population-based interactive physiologically based pharmacokinetic (iPBPK) modeling platform: example for flunixin meglumine administration",
abstract = "Violative chemical residues in animal-derived food products affect food safety globally and have impact on the trade of international agricultural products. The Food Animal Residue Avoidance Databank program has been developing scientific tools to provide appropriate withdrawal interval (WDI) estimations after extralabel drug use in food animals for the past three decades. One of the tools is physiologically based pharmacokinetic (PBPK) modeling, which is a mechanistic-based approach that can be used to predict tissue residues and WDIs. However, PBPK models are complicated and difficult to use by non-modelers. Therefore, a user-friendly PBPK modeling framework is needed to move this field forward. Flunixin was one of the top five violative drug residues identified in the United States from 2010 to 2016. The objective of this study was to establish a web-based user-friendly framework for the development of new PBPK models for drugs administered to food animals. Specifically, a new PBPK model for both cattle and swine after administration of flunixin meglumine was developed. Population analysis using Monte Carlo simulations was incorporated into the model to predict WDIs following extralabel administration of flunixin meglumine. The population PBPK model was converted to a web-based interactive PBPK (iPBPK) framework to facilitate its application. This iPBPK framework serves as a proof-of-concept for further improvements in the future and it can be applied to develop new models for other drugs in other food animal species, thereby facilitating the application of PBPK modeling in WDI estimation and food safety assessment.",
keywords = "Drug residues, Flunixin, Food Animal Residue Avoidance Databank (FARAD), Food safety, Interactive physiologically based pharmacokinetic (iPBPK) model, Withdrawal intervals (WDIs)",
author = "Miao Li and Cheng, {Yi Hsien} and Chittenden, {Jason T.} and Baynes, {Ronald E.} and Tell, {Lisa A} and Davis, {Jennifer L.} and Vickroy, {Thomas W.} and Riviere, {Jim E.} and Zhoumeng Lin",
year = "2019",
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doi = "10.1007/s00204-019-02464-z",
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AU - Li, Miao

AU - Cheng, Yi Hsien

AU - Chittenden, Jason T.

AU - Baynes, Ronald E.

AU - Tell, Lisa A

AU - Davis, Jennifer L.

AU - Vickroy, Thomas W.

AU - Riviere, Jim E.

AU - Lin, Zhoumeng

PY - 2019/1/1

Y1 - 2019/1/1

N2 - Violative chemical residues in animal-derived food products affect food safety globally and have impact on the trade of international agricultural products. The Food Animal Residue Avoidance Databank program has been developing scientific tools to provide appropriate withdrawal interval (WDI) estimations after extralabel drug use in food animals for the past three decades. One of the tools is physiologically based pharmacokinetic (PBPK) modeling, which is a mechanistic-based approach that can be used to predict tissue residues and WDIs. However, PBPK models are complicated and difficult to use by non-modelers. Therefore, a user-friendly PBPK modeling framework is needed to move this field forward. Flunixin was one of the top five violative drug residues identified in the United States from 2010 to 2016. The objective of this study was to establish a web-based user-friendly framework for the development of new PBPK models for drugs administered to food animals. Specifically, a new PBPK model for both cattle and swine after administration of flunixin meglumine was developed. Population analysis using Monte Carlo simulations was incorporated into the model to predict WDIs following extralabel administration of flunixin meglumine. The population PBPK model was converted to a web-based interactive PBPK (iPBPK) framework to facilitate its application. This iPBPK framework serves as a proof-of-concept for further improvements in the future and it can be applied to develop new models for other drugs in other food animal species, thereby facilitating the application of PBPK modeling in WDI estimation and food safety assessment.

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