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Toxicol Sci. 2017 Jul 1;158(1):23-35. doi: 10.1093/toxsci/kfx070.

Performance Assessment and Translation of Physiologically Based Pharmacokinetic Models From acslX to Berkeley Madonna, MATLAB, and R Language: Oxytetracycline and Gold Nanoparticles As Case Examples.

Author information

1
Institute of Computational Comparative Medicine (ICCM), Department of Anatomy and Physiology, College of Veterinary Medicine, Kansas State University, Manhattan, Kansas 66506.
2
Department of Mathematics, College of Arts and Sciences, Kansas State University, Manhattan, Kansas 66506.
3
Department of Epidemiology and Biostatistics, College of Public Health, The University of Georgia, Athens, Georgia 30602.
4
Department of Statistics, College of Arts and Sciences, Kansas State University, Manhattan, Kansas 66506.
5
Department of Environmental and Radiological Health Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, Colorado 80523.
6
Ray Yang Consulting LLC, Fort Collins, Colorado 80526.
7
Division of Biochemical Toxicology, National Center for Toxicological Research, U.S. Food and Drug Administration, Jefferson, Arkansas 72079.

Abstract

Many physiologically based pharmacokinetic (PBPK) models for environmental chemicals, drugs, and nanomaterials have been developed to aid risk and safety assessments using acslX. However, acslX has been rendered sunset since November 2015. Alternative modeling tools and tutorials are needed for future PBPK applications. This forum article aimed to: (1) demonstrate the performance of 4 PBPK modeling software packages (acslX, Berkeley Madonna, MATLAB, and R language) tested using 2 existing models (oxytetracycline and gold nanoparticles); (2) provide a tutorial of PBPK model code conversion from acslX to Berkeley Madonna, MATLAB, and R language; (3) discuss the advantages and disadvantages of each software package in the implementation of PBPK models in toxicology, and (4) share our perspective about future direction in this field. Simulation results of plasma/tissue concentrations/amounts of oxytetracycline and gold from different models were compared visually and statistically with linear regression analyses. Simulation results from the original models were correlated well with results from the recoded models, with time-concentration/amount curves nearly superimposable and determination coefficients of 0.86-1.00. Step-by-step explanations of the recoding of the models in different software programs are provided in the Supplementary Data. In summary, this article presents a tutorial of PBPK model code conversion for a small molecule and a nanoparticle among 4 software packages, and a performance comparison of these software packages in PBPK model implementation. This tutorial helps beginners learn PBPK modeling, provides suggestions for selecting a suitable tool for future projects, and may lead to the transition from acslX to alternative modeling tools.

KEYWORDS:

Berkeley Madonna; MATLAB; PBPK modeling; R language; acslX

PMID:
28402537
DOI:
10.1093/toxsci/kfx070
[Indexed for MEDLINE]

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