Characterization of Lipophilicity and Blood Partitioning of Pyrrolizidine Alkaloids and Their N-Oxides In Vitro and In Silico for Toxicokinetic Modeling.

ABSTRACT: Lipophilicity and blood partitioning are important determinants for predicting toxicokinetics using physiologically-based toxicokinetic modeling. In this study, the logarithm of the n-octanol : water partition coefficient and the blood-to-plasma concentration ratio were, for the first time, experimentally determined for the pyrrolizidine alkaloids intermedine, lasiocarpine, monocrotaline, retrorsine, and their N-oxides. Validated in vitro assays for determination of the n-octanol : water partition coefficient (miniaturized shake-flask method) and the blood-to-plasma conentration ratio (LC-MS/MS-based depletion assay) were compared to an ensemble of in silico models. The experimentally determined octanol : water partition coefficient indicates a higher affinity o

SUBMITTER: Lehmann A 

PROVIDER: S-EPMC12021451 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature