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July - September 2021


Sniffing for science

Annegret Grimm-Seyfarth with species tracking dog "Zammy", a Border Collie. Photo: André Künzelmann / UFZ Annegret Grimm-Seyfarth with species tracking dog "Zammy", a Border Collie. Photo: André Künzelmann / UFZ Article in English follows


July 2021








Evaluation of algorithms for prediction of unbound fractions in blood

red blood cells UFZ scientists have evaluated the most commonly used algorithms for prediction of unbound fractions of pharmaceutical compounds in the human body. Only the free fraction of an absorbed pharmaceutical compound can take a medical effect. The method and the results are described in a recent paper.

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, UFZ scientists 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.

Paper here

July 2021