Hepatocytes provide an integrated model to study drug metabolism and disposition. Suspended and sandwich cultured hepatocytes have limitations in determining hepatocellular drug concentrations due to loss of polarity or significant decrease in expression of enzymes and transporters. Under-prediction of the extent of glucuronidation is also a concern for these hepatocyte models. Faldaprevir is an HCV protease inhibitor in late stage development that has demonstrated significant liver enrichment in in vivo rat models based on QWBA and liver to plasma AUC ratio. In bile duct cannulated rats the primary biliary metabolite was a glucuronide. It is difficult to assess liver enrichment in humans for ethical concerns and a lack of in vitro and in vivo correlation of glucuronidation has been reported. The current study was conducted to verify whether an hepatocyte model, rat HepatoPac, could overcome some of these limitations and provide validity for follow up studies with human HepatoPac. With rat HepatoPac, liver enrichment values averaged 34-fold and were consistent with rat QWBA (26.8-fold) and in vivo data (42-fold). In contrast, liver enrichment in suspended hepatocytes was only 2.8-fold. Furthermore, the extent of faldaprevir glucuronidation in HepatoPac studies was in agreement with in vivo, with glucuronidation as the major pathway (96%). Suspended rat hepatocytes did not generate the glucuronide or two key hydroxylated metabolites which were observed in vivo. Overall, our studies suggest that HepatoPac is a promising in vitro model to predict in vivo liver enrichment and metabolism, especially for glucuronidation, and has demonstrated superiority over suspended hepatocytes.