Evidence-based absorption, distribution, metabolism, excretion (ADME) and its interplay with alternative toxicity methods

Tsaioun, Katya; Blaauboer, Bas J.; Hartung, Thomas

Evidence-based absorption, distribution, metabolism, excretion (ADME) and its interplay with alternative toxicity methods

Dateien

Tsaioun_0-376941.pdfGröße: 2.55 MBDownloads: 1038

Datum

2016

Autor:innen

Tsaioun, Katya

Blaauboer, Bas J.

Hartung, Thomas

Open Access-Veröffentlichung

Open Access Gold

Sammlungen

Biologie

Publikationstyp

Zeitschriftenartikel

Publikationsstatus

Published

Erschienen in

Alternatives to Animal Experimentation : ALTEX. 2016, 33(4), pp. 343-358. ISSN 0946-7785. eISSN 1868-8551. Available under: doi: 10.14573/altex.1610101

Zusammenfassung

ADME (absorption, distribution, metabolism, elimination) has rapidly evolved over the past two decades, creating a unique interdisciplinary interface between medicinal chemists, biologists, formulators, toxicologists, clinicians, and regulators across industries, but has advanced most rapidly in the pharmaceutical industry. The implementation of ADME profiling of drug candidates, in conjunction with biological efficacy and safety optimization, has dramatically reduced pharmacokinetic drug failures in clinical trials and has become a lingua franca between disciplines that are involved in drug development. This article briefly reviews the basics and current state-of-the-art of ADME and the major lessons from the pharmaceutical industry on its efficient use, points out the importance of defining ADME properties leading to toxicity across industries for safety and toxicity prediction of chemicals, and raises the issues of quality, reliability, and reproducibility of tests and inclusion of ADME under the umbrella of evidence-based toxicology. Increasingly, in vitro results are used to inform ADME assessments and computer modeling. The aspects of kinetics of substances in cellular models themselves, however, are still too often neglected. ADME information will play a critical role in establishing quantitative in vitro to in vivo extrapolations (QIVIVE), integrated testing strategies, and systems toxicology approaches.

Fachgebiet (DDC)

570 Biowissenschaften, Biologie

Schlagwörter

ADME, pharmacokinetics (PK), physiologically-based pharmacokinetic (PBPK) model, systems toxicology, evidence-based toxicology

Zitieren

ISO 690

TSAIOUN, Katya, Bas J. BLAAUBOER, Thomas HARTUNG, 2016. Evidence-based absorption, distribution, metabolism, excretion (ADME) and its interplay with alternative toxicity methods. In: Alternatives to Animal Experimentation : ALTEX. 2016, 33(4), pp. 343-358. ISSN 0946-7785. eISSN 1868-8551. Available under: doi: 10.14573/altex.1610101

BibTex

@article{Tsaioun2016Evide-37782,
  year={2016},
  doi={10.14573/altex.1610101},
  title={Evidence-based absorption, distribution, metabolism, excretion (ADME) and its interplay with alternative toxicity methods},
  number={4},
  volume={33},
  issn={0946-7785},
  journal={Alternatives to Animal Experimentation : ALTEX},
  pages={343--358},
  author={Tsaioun, Katya and Blaauboer, Bas J. and Hartung, Thomas}
}

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