As pharmaceutical companies pursue the development of more stable compounds that enable extended dosing regimens, medicinal chemists are becoming more adept at synthesizing these entities. This puts increasing pressure on DMPK departments to accurately predict turnover. With only a 4-hour lifespan, conventional suspension cultures cannot be used to determine clearance for these slowly metabolized, stable compounds. HepatoPac™ is an in vitro micropatterened co-culture of primary hepatocytes that remains functional and viable for up to four weeks. Its extended longevity and full complement of active phase I and phase II enzymes as well as transporters make it an ideal platform for predicting the metabolic stability of high, medium and low turnover compounds. When compared to industry-standard suspension cultures, HepatoPac’s ability to perform long-term continuous incubations of stable compounds results in better turnover. Its proprietary architecture promotes intact bile caniliculi and active drug transporter activity, enabling studies of mechanistic clearance.