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ORIGINAL RESEARCH article

Front. Pharmacol.
Sec. Drug Metabolism and Transport
Volume 15 - 2024 | doi: 10.3389/fphar.2024.1462193
This article is part of the Research Topic ADME of Drugs to Treat Infectious Diseases View all 3 articles

stormTB: A web-based simulator of a murine minimal-PBPK model for anti-tuberculosis treatments

Provisionally accepted
Roberto Visintainer Roberto Visintainer 1Anna Fochesato Anna Fochesato 1,2Daniele Boaretti Daniele Boaretti 1Stefano Giampiccolo Stefano Giampiccolo 1,3Shayne Watson Shayne Watson 4Micha Levi Micha Levi 4Federico Reali Federico Reali 1*Luca Marchetti Luca Marchetti 1,5*
  • 1 Fondazione The Microsoft Research - University of Trento Centre for Computational and Systems Biology, Rovereto, Italy
  • 2 Department of Mathematics, University of Trento, Trento, Trentino-Alto Adige/Südtirol, Italy
  • 3 Department of Engineering and Information Science, University of Trento, Trento, Trentino-Alto Adige/Südtirol, Italy
  • 4 Bill & Melinda Gates Medical Research Institute, Cambridge, Maryland, United States
  • 5 Department of Cellular, Computational and Integrated Biology, University of Trento, Povo, Italy

The final, formatted version of the article will be published soon.

    Introduction: Tuberculosis (TB) poses a significant threat to global health, with millions of new infections and approximately one million deaths annually. Various modeling efforts have emerged, offering tailored data-driven and physiologically-based solutions for novel and historical compounds. However, this diverse modeling panorama may lack consistency, limiting result comparability. Drug-specific models are often tied to commercial software and developed on various platforms and languages, potentially hindering access and complicating the comparison of different compounds. Methods: This work introduces stormTB: SimulaTOr of a muRine Minimal-pbpk model for anti-TB drugs. It is a web-based interface for our minimal physiologically based pharmacokinetic (mPBPK) platform, designed to simulate custom treatment scenarios for tuberculosis in murine models. The app facilitates visual comparisons of pharmacokinetic profiles, aiding in assessing drug-dose combinations. Results: The mPBPK model, supporting 11 anti-TB drugs, offers a unified perspective, overcoming the potential inconsistencies arising from diverse modeling efforts. The app, publicly accessible, provides a user-friendly environment for researchers to conduct what-if analyses and contribute to collective TB eradication efforts. The tool generates comprehensive visualizations of drug concentration profiles and pharmacokinetic/pharmacodynamic indices for TB-relevant tissues, empowering researchers in the quest for more effective TB treatments. stormTB is freely available at the link: https://apps.cosbi.eu/stormTB.

    Keywords: Physiologically based modeling, pharmacokinetics, Pharmacodynamics, ADME, Tuberculosis, web interface

    Received: 09 Jul 2024; Accepted: 18 Dec 2024.

    Copyright: © 2024 Visintainer, Fochesato, Boaretti, Giampiccolo, Watson, Levi, Reali and Marchetti. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence:
    Federico Reali, Fondazione The Microsoft Research - University of Trento Centre for Computational and Systems Biology, Rovereto, Italy
    Luca Marchetti, Fondazione The Microsoft Research - University of Trento Centre for Computational and Systems Biology, Rovereto, Italy

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.