With the trend toward developing more stable compounds and extended dosing regimens, DMPK departments need to accurately predict turnover of even slowly metabolized compounds. The extremely limited lifespan of conventional suspension cultures precludes their use in determining clearance for these stable compounds.
HepatoPac® is an in vitro micropatterened co-culture of primary hepatocytes that retains functionality 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 metabolic stability predictions. Additionally, HepatoPac's proprietary architecture promotes intact bile caniliculi and active drug transporter activity, enabling studies of mechanistic clearance.
Extended Functionality Produces Increased Sensitivity
Given HepatoPac's longevity and stable enzymatic functions, the platform allows for the complete metabolism of pharmaceutical compounds. HepatoPac has been shown to be 20% more predictive in detecting primary and secondary excretory metabolites.
HepatoPac for Metabolic Stability Studies
Access the highly predictive power of HepatoPac® using our Human HepatoPac® Metabolic Stability Kit or through Hepregen Contract DMPK Services.
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Representative plot of parent compound depletion in HepatoPac Metabolic Stability assays for commercially available low (Theophylline), intermediate (Erythromycin), and high (Verapamil) clearance compounds.
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The strong in vitro to in vivo correlation observed in HepatoPac allows for accurate predictive clearance.
|Publication||Meeting the challenge of predicting hepatic clearance of compounds slowly metabolized by cytochrome P450 using a novel hepatocyte model, HepatoPac Drug Metab Dispos. Vol. 41(12), p 2024-2032 (2013).|
|Poster||Be Careful What You Ask for: Challenges of Predicting Human Clearance for a Low Metabolic Turnover Compound|