Chemical concentrations in cell culture compartments (C5) - free concentrations.

ola Kala shared this article with you from Inoreader Chemical concentrations in cell culture compartments (C5) - free concentrations. Μέσω Mitteleuropäische Gesellschaft für Alternativmethoden zu Tierversuchen Johns Hopkins Center for Alternatives to Animal Testing European Society for Alternatives to Animal Testing Chemical concentrations in cell culture compartments (C5) - free concentrations. ALTEX. 2020;37(4):693-708 Authors: Kisitu J, Hollert H, Fisher C, Leist M Abstract 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 un derlying 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. PMID: 33080039 [PubMed - as supplied by publisher] View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.