Abstract
When present in blood, most chemicals tend to bind to the plasma protein albumin. For distribution into surrounding tissues, desorption from albumin is necessary, because only the unbound form of a chemical is assumed to be able to cross cell membranes. For metabolism of chemicals, the liver is a particularly important organ. One potentially limiting step for hepatic uptake of the chemicals is desorption from albumin, because blood passes the human liver within seconds. Desorption kinetics from albumin can thus be an important parameter for our pharmacokinetic and toxicokinetic understanding of chemicals. This work presents a dataset of measured desorption rate constants and reveals a possibility for their prediction. Additionally, the obtained extraction profiles directly indicate physiological relevance of desorption kinetics, because desorption of the test chemicals is still incomplete after time frames comparable to the residence time of blood in the liver.
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Acknowledgements
The authors thank Robert Köhler and Anett Georgi for technical support, Andrea Pfennigsdorff for lab assistance, Benjamin Schwarz for facilitating the measurement of a breakthrough curve and Satoshi Endo and Beate Escher for useful comments on our work. Additionally, we would like to thank the reviewers for their valuable comments which improved our manuscript strongly.
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Krause, S., Ulrich, N. & Goss, KU. Desorption kinetics of organic chemicals from albumin. Arch Toxicol 92, 1065–1074 (2018). https://doi.org/10.1007/s00204-017-2117-4
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DOI: https://doi.org/10.1007/s00204-017-2117-4