The importance of protein binding for the in vitro-in vivo extrapolation (IVIVE)-example of ibuprofen, a highly protein-bound substance.

摘要: A physiologically based human kinetic model (PBHKM) was used to predict the in vivo ibuprofen dose leading same concentration–time profile as measured cultured hepatic cells (Truisi et al. Toxicol Lett 233(2):172–186, 2015). We parameterized PBHKM with data from an study. Tissue partition coefficients were calculated by algorithm and also derived experimental vitro for liver. The predicted plasma excellent agreement when liver coefficient (3.01) demonstrating values line findings obtained postmortem tissues. results less adequate on (11.1). doses necessary reach concentrations 3610 mg using best fitting a of 3.01 compared 2840 mg 11.1. found that this difference is possibly attributable between protein binding (99.9 %) (nearly zero) highly dependent binding. Hence, fraction freely diffusible tissue several times higher than vivo. In consequence, extrapolating toxicity, it important consider non-intended vitro/in differences concentration which may occur due low content medium.