Kunze A Huwyler J Poller B Gutmann H Camenisch G 2014 Renal clearance is a key determinant of the elimination of drugs. To date, only few in vitro-in vivo extrapolation (IVIVE) approaches have been described to predict the renal organ clearance as the net result of glomerular filtration, tubular secretion, and tubular reabsorption. In this study, we measured in LLC-PK1 cells the transport of 20 compounds that cover all four classes of the Biopharmaceutical Drug Disposition System. These data were incorporated into a novel kidney model to predict all renal clearance processes in human. We showed that filtration and secretion were main contributors to the renal organ clearance for all compounds, whereas reabsorption was predominant for compounds assigned to classes 1 and 2. Our results suggest that anionic drugs were not significantly secreted in LLC-PK1 cells, resulting in under-predicted clearances. When all study compounds were included a high overall correlation between the reported and predicted renal organ clearances was obtained (R² = 0.83). The prediction accuracy in terms of percentage within twofold and threefold error was 70% and 95%, respectively. In conclusion, our novel IVIVE method allowed to predict the human renal organ clearance and the contribution of each underlying process. https://sonar.ch/global/documents/232234 eng info:eu-repo/semantics/altIdentifier/doi/10.1002/jps.23851 info:eu-repo/semantics/altIdentifier/pmid/24549735 Journal of pharmaceutical sciences. - 2014 LLC-PK1 cell line clearance prediction drug transport in vitro models in vitro-in vivo correlations (IVIVC) membrane transport permeability pharmacokinetics renal clearance renal reabsorption Absorption Algorithms Animals Biological Transport Cell Membrane Permeability Glomerular Filtration Rate Humans Kidney Kidney Tubules LLC-PK1 Cells Metabolic Clearance Rate Models, Biological Permeability Pharmaceutical Preparations Pharmacokinetics Reproducibility of Results Swine In vitro-in vivo extrapolation method to predict human renal clearance of drugs. http://purl.org/coar/resource_type/c_6501