Chemical concentrations in cell culture compartments (C5) : free concentrations

Kisitu, Jaffar; Hollert, Henner; Fisher, Ciarán; Leist, Marcel

Chemical concentrations in cell culture compartments (C5) : free concentrations

Dateien

Kisitu_2-1t853tp955kuk7.pdfGröße: 1.71 MBDownloads: 220

Datum

2020

Autor:innen

Kisitu, Jaffar

Hollert, Henner

Fisher, Ciarán

Leist, Marcel

Angaben zur Forschungsförderung

European Union (EU): 681002

Projekt

EUToxRisk21

Open Access-Veröffentlichung

Open Access Gold

Sammlungen

Biologie

Publikationstyp

Zeitschriftenartikel

Publikationsstatus

Published

Erschienen in

Alternatives to Animal Experimentation : ALTEX. Springer Spektrum. 2020, 37(4), pp. 693-708. ISSN 1868-596X. eISSN 1868-8551. Available under: doi: 10.14573/altex.2008251

Zusammenfassung

In biological systems (cell culture media, cells, body fluids), drugs/toxicants are usually not freely dissolved but partially bound to biomolecules; only a fraction of the chemical is free/unbound (fu). To predict pharmacological effects and toxicity, it is important that the fu of the drug is known. As the differences between free and nominal concentrations are determined by test system parameters (e.g., the protein and lipid content, and the type of surface material), comparison of nominal concentrations between two different new approach methods (NAM) may lead to faulty conclusions. The same problem exists when in vitro concentrations are compared to those in human subjects. Therefore, the respective fu of a chemical in a test system needs to be determined for in vitro-to-in vivo extrapolations (IVIVE). Besides direct measurements, prediction models can help to obtain fu. Here we describe a simplified approach to approximate fu and provide background information on the underlying assumptions. Comparative predictions and measurements of fu of various drugs are shown to exemplify the approach. Basic input data, like protein and lipid concentrations, are also provided. Beyond such test systems data, the only required chemical-specific inputs are the lipophilicity of the candidate drug and its ionization state, as determined by the dissociation constants of its acidic or basic groups. This overview is intended to be used by any lab scientist without specific toxicokinetics training to obtain an estimate of fu in a given cell culture medium.

Fachgebiet (DDC)

570 Biowissenschaften, Biologie

Zitieren

ISO 690

KISITU, Jaffar, Henner HOLLERT, Ciarán FISHER, Marcel LEIST, 2020. Chemical concentrations in cell culture compartments (C5) : free concentrations. In: Alternatives to Animal Experimentation : ALTEX. Springer Spektrum. 2020, 37(4), pp. 693-708. ISSN 1868-596X. eISSN 1868-8551. Available under: doi: 10.14573/altex.2008251

BibTex

@article{Kisitu2020Chemi-51796,
  year={2020},
  doi={10.14573/altex.2008251},
  title={Chemical concentrations in cell culture compartments (C5) : free concentrations},
  number={4},
  volume={37},
  issn={1868-596X},
  journal={Alternatives to Animal Experimentation : ALTEX},
  pages={693--708},
  author={Kisitu, Jaffar and Hollert, Henner and Fisher, Ciarán and Leist, Marcel}
}

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