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CYP3A4 activity levels in HepatoPac™ stabilize after a few days and exhibit sustained activity for several weeks.
DMPK Services
Hepregen offers a range of DMPK services using our HepatoPac™ platform. HepatoPac’s extended longevity and functionality as a result of the organized hepatocyte microenvironment result in more predictive in vivo outcomes than conventional in vitro models. HepatoPac's key benefits for DMPK applications include:
- Higher CYP activities
- More predictive of in vivo outcomes
- Able to screen stable and low turnover compounds
Hepregen provides DMPK services in the following models:
- Human
- Rat
- Monkey
- Dog (In development. Contact us for additional information.)
Metabolite Identification
Identifying drug metabolites is a key process in drug development. The ability to correctly predict human in vivo metabolites can save both time and money in the clinic. Metabolites discovered in the clinic must be characterized and tested for safety. Not only does this inquiry require additional resources, but it also delays the product launch resulting in a loss of potential revenue. More predictive platforms, such as HepatoPac™, help researchers make better selections among potential candidate molecules in order to avoid surprises in the clinic.
HepatoPac™ offers "the highest performance among in vitro metabolism systems to predict major human in vitro metabolites." Drug Metab. and Disp., Vol. 38(10), p. 1900-1905 (2010)
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.
- The most predictive in vitro platform
- Conduct 7-day metabolism incubations without media changes
- Study slowly metabolized drugs
- Identify metabolites other models miss
Featured Resources
Case Study: Ability of a Micropatterned Hepatocyte Co-culture System to Generate Major Human Drug Metabolites
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Publication: Assessment of a Micropatterned Hepatocyte Coculture System to Generate Major Human Excretory and Circulating Drug Metabolites
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Intrinsic Clearance
Generating accurate in vitro intrinsic clearance or metabolic stability data is essential for predicting in vivo human clearance and establishing a safe dose range in early clinical studies. Conventional primary hepatocytes in suspension are routinely used to determine drug clearance, but their limited viability (only a few hours), severely limits the ability of suspension hepatocytes to evaluate the metabolic stability of low clearance compounds.
HepatoPac™ can be used for continuous incubations for up to 7 days without media change. The platform’s longevity combined with its physiologically-relevant metabolism make it is an ideal platform for predicting intrinsic clearance of high, medium and low clearance compounds.
- Predict clearance of low turnover compounds
- Provides physiologically-relevant metabolism
- A single platform for high, medium and low turnover compounds
HepatoPac's high in vitro to in vivo correlations make the platform an ideal system for clearance predictions in human and pre-clinical species models.
Featured Resources
Application Note: Addressing the Challenges of In Vitro Clearance Prediction of Low Turnover Compounds.
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Poster: Be Careful What You Ask for: Challenges of Predicting Human Clearance for a Low Metabolic Turnover Compound, ELND006
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Induction Studies
The induction or inhibition of CYP450 enzymes can be an important aspect of clinical drug-drug interactions. HepatoPac™ can be a valuable platform for the study of CYP450 enzyme induction. Because of HepatoPac's extended longevity, it is the ideal platform to investigate long-term induction or inhibition.
Featured Resources
Whitepaper: HepatoPac™: A Bioengineered Micro-Liver Platform for Predictive Drug Metabolism and Toxicity Studies
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Drug Transporter Assays
Membrane transporters can have important effects on pharmacokinetics and drug exposure as mentioned in the FDA's Guidance for Industry on Drug Interaction Studies*. HepatoPac™’s improved functionality and longevity have made it a valuable tool in assessing transporter-mediated uptake and efflux.
HepatoPac expresses most drug transporters and exhibits higher levels of transporter-mediated compound uptake compared to sandwich cultures. Furthermore, HepatoPac retains optimal transporter functions for several weeks compared to days in sandwich cultures. As a result of microengineering, the HepatoPac cellular architecture creates a highly reproducible in vitro model exhibiting a consistent and extensive bile canalicular network.
- High levels of transport expression for several weeks
- Confers an extensive bile canalicular network
- Highly reproducible platform
- Retains metabolic capacity and function
Featured Resources
Whitepaper: HepatoPac™: A Bioengineered Micro-Liver Platform for Predictive Drug Metabolism and Toxicity Studies
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Poster: Micropatterned Primary Hepatocyte Co-Cultures for Drug Metabolism and Toxicity Studies
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Related Information
Featured Downloads
New Met ID Case Study Released
Ability of a Micropatterned Hepatocyte Co-culture System to Generate Major Human Drug Metabolites
Read MoreHepatoPac™-Kupffer Cell Inflammation Model
App. Note - A Micropatterned Hepatocyte-Kupffer Cell Co-culture System to Study Inflammation-Drug Interactions
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