Metabolic Stability and Clearance

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 there use in determining clearance for these stable compounds.

Metabolite Stability and Clearance in HepatoPac
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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

  • 7-day incubation without media changes allows accurate results for low turnover compounds
  • Unmatched longevity and functionality provides physiologically-relevant metabolism
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  • Proven high level of in vitro to in vivo predictive correlation (IVIVC)
  • In vitro stratification of low turnover compounds in a chemical series
  • Multiple species platform (human, rat, dog, etc.) for increased in vitro predictive power
  • Examine high, medium and low turnover compounds using a single platform

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.

Technical Resources

Type Title
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