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The use of the Göttingen minipig as an animal model for drug safety testing and prediction of human pharmacokinetics (PK) continues to gain momentum in pharmaceutical research and development. The aim of this study was to evaluate  in vitro  to  in vivo  extrapolation (IVIVE) methodologies for prediction of hepatic, metabolic clearance ( CL hep,met )  in Göttingen minipig, using a comprehensive set of compounds.In vivo  clearance was determined in Göttingen minipig by intravenous cassette dosing and hepatocyte intrinsic clearance, plasma protein binding and non-specific incubation binding were determined  in vitro . Prediction of  CL hep,metwas performed by IVIVE using conventional and adapted formats of the well-stirred liver model.The best prediction of  in vivo CL hep,metfrom scaled  in vitro  kinetic data was achieved using an empirical correction factor based on a ‘regression offset’ of the IVIV relationship.In summary, these results expand the  in vitro  and  in vivo  PK knowledge in Göttingen minipig. We show regression corrected IVIVE provides superior prediction of  in vivo CL hep,metin minipig offering a practical, unified scaling approach to address systematic under-predictions. Finally, we propose a reference set for researchers to establish their own ‘lab-specific’ regression correction for IVIVE in minipig. The use of the Göttingen minipig as an animal model for drug safety testing and prediction of human pharmacokinetics (PK) continues to gain momentum in pharmaceutical research and development. The aim of this study was to evaluate  in vitro  to  in vivo  extrapolation (IVIVE) methodologies for prediction of hepatic, metabolic clearance ( CL hep,met )  in Göttingen minipig, using a comprehensive set of compounds. In vivo  clearance was determined in Göttingen minipig by intravenous cassette dosing and hepatocyte intrinsic clearance, plasma protein binding and non-specific incubation binding were determined  in vitro . Prediction of  CL hep,metwas performed by IVIVE using conventional and adapted formats of the well-stirred liver model. The best prediction of  in vivo CL hep,metfrom scaled  in vitro  kinetic data was achieved using an empirical correction factor based on a ‘regression offset’ of the IVIV relationship. In summary, these results expand the  in vitro  and  in vivo  PK knowledge in Göttingen minipig. We show regression corrected IVIVE provides superior prediction of  in vivo CL hep,metin minipig offering a practical, unified scaling approach to address systematic under-predictions. Finally, we propose a reference set for researchers to establish their own ‘lab-specific’ regression correction for IVIVE in minipig.

xenobiotica

Characterisation of intravenous pharmacokinetics in Göttingen minipig and clearance prediction using established  in vitro  to  in vivo  extrapolation methodologies