Understanding the biokinetics of ibuprofen after single and repeated treatments in rat and human in vitro liver cell systems

摘要: Common in vitro toxicity testing often neglects the fate and intracellular concentration of tested compounds, potentially limiting predictability results for vivo extrapolation. We used long-term cultures primary rat (PRH) human hepatocytes (PHH) HepaRG cells to characterise model biokinetic profile ibuprofen (IBU) after single daily repeated exposure (14 days) two concentrations. A cross-model comparison was carried out at 100μM, roughly corresponding therapeutic plasma concentration. Our showed that IBU uptake rapid a dynamic equilibrium reached within 1 or 2 days. All three cell systems efficiently metabolised IBU. In terms species-differences, our data mirrored known results. Although no bioaccumulation observed, higher PRH due 10-fold lower metabolic clearance compared human-derived cells. cells, metabolism increased over time, but not related treatment. PHH, low CYP2C9 activity, major IBU-metabolising CYP, led an cytotoxicity. high inter-individual variability seen whereas were more reproducible models. concentrations time differed from found under similar conditions.