TY  - JOUR
A1  - Kisitu, Jaffar
A1  - Hollert, Henner
A1  - Fisher, Ciarán
A1  - Leist, Marcel
T1  - Chemical concentrations in cell culture compartments (C5) – free concentrations
T2  - Alternatives to animal experimentation : ALTEX
N2  - 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.
Y1  - 2020
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/57418
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-574186
SN  - 1868-8551
SN  - 1868-596X
VL  - 37
IS  - 4
SP  - 693
EP  - 708
PB  - Springer Spektrum
CY  - Heidelberg
ER  -