Prediction of Unbound Fractions for in Vitro–in Vivo Extrapolation of Biotransformation Data
| Autor: | Sophia Krause, Kai-Uwe Goss |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
0303 health sciences
Chromatography Chemistry Extrapolation Sorption General Medicine 010501 environmental sciences Toxicology 01 natural sciences In vitro 03 medical and health sciences Biotransformation Surface-area-to-volume ratio In vivo Yield (chemistry) In vitro in vivo 030304 developmental biology 0105 earth and related environmental sciences |
| Zdroj: | Chemical Research in Toxicology. 34:7-11 |
| ISSN: | 1520-5010 0893-228X |
| DOI: | 10.1021/acs.chemrestox.0c00349 |
| Popis: | For in vitro-in vivo extrapolation of biotransformation data, the different sorptive environments in vitro and in vivo need to be considered. The most common approach for doing so is using the ratio of unbound fractions in vitro and in vivo. In the literature, several algorithms for prediction of these unbound fractions are available. In this study, we present a theoretical evaluation of the most commonly used algorithms for prediction of unbound fractions in S9 assays and blood and compare prediction results with empirical values from the literature. The results of this analysis prove a good performance of "composition-based" algorithms, i.e. algorithms that represent the inhomogeneous composition of in vitro assay and in vivo system and describe sorption to the individual components (lipids, proteins, water) in the same way. For strongly sorbing chemicals, these algorithms yield constant values for the ratio of unbound fractions in vitro and in vivo. This is mechanistically plausible, because in these cases, the chemicals are mostly bound, and the ratio of unbound fractions is determined by the volume ratio of sorbing components in both phases. |
| Databáze: | OpenAIRE |
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