Hepatocyte relay method was recently developed for hepatic intrinsic clearance prediction of low turnover compounds. However, its application was limited by one-week long experimental procedure and complicated data analysis. In order to simplify this method, a new protocol was established by incorporating our standardized regular hepatocyte stability assay presented previously. This new method was validated using ten commercially available drugs with very low values of human in vivo clearance. Comparison between the regular and relay methods were examined. Results have shown that the simplified relay method significantly improved data quality (e.g. higher R~2 values), with very good in vitro-in vivo clearance correlation (IVIVC). Therefore, we have demonstrated that this simplified relay method could serve as a valuable tool for investigating compounds with ultra low turnovers.
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