May_PR_slider.png

 
Metabolite Identification and Profiling

Accurate identification of drug metabolites is a key aspect of drug development. Moreover, the ability to correctly predict human in vivo metabolites can save both time and money in clinical development. Metabolites discovered in the clinic must be characterized and tested for safety. Because the exclusivity period for new drug sales is limited, not only does this exercise require additional product development effort and resources, but it also delays the product launch, resulting in major loss of revenue. More predictive platforms, such as HepatoPac®, help researchers make better selections among potential candidate molecules, thus avoiding surprises in the clinic.

Access the predictive power of HepatoPac using our HepatoPac MetID Kits or through Hepregen Contract DMPK Services.  

In May of 2015, Hepregen announced a co-marketing agreement for a service to be offered with SCIEX, the gold-standard in LC/MS technology.  This new Comprehensive Met ID Solution combines the increased metabolite production of HepatoPac's superior cellular machinery and NEW multi-species plate with SCIEX's TripleTOF®, SWATH™ Acquisition, and Metabolite Pilot™ software to generate, detect and analyze more metabolites than any other Met ID solution available today.  Click here to learn more.

SWATH_ACQUISITION

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)
Contact Ascendance-Hepregen  Download Media Pack   Watch Video

 

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.

  • The most predictive in vitro platform
  • Conduct 7-day metabolism incubations without media changes
  • Study  slowly metabolized drugs
  • Identify metabolites other models miss


HepatoPac produces more Phase I, Phase II and Phase III metabolites than suspension hepatocytes
Click to enlarge

Success rate of Human HepatoPac versus primary human hepatocyte suspension culture production of Phase I, Phase II, Primary and Secondary Metabolites compared to clinical observations.

Superior Performance of HepatoPacCo-cultures in Met ID Studies

HepatoPac co-culture technology performance exceeds that of other standard in vitro models such as microsomes, S-9 fractions and primary hepatocyte suspensions in metabolite identification comparison studies. HepatoPac cultures identified an average of 79% of the total metabolites previously observed in the clinic (75% of total circulating metabolites and 83% of total excretory metabolites). In contrast, the various traditional methods produced between 43-53% of the total circulating metabolites and 49-64% of the total excretory metabolites. HepatoPac cultures produced 15 of 16 primary circulating and 14 of 16 primary excretory metabolites highlighting the comprehensive nature of HepatoPac results. Additionally, because HepatoPac co-cultures are stable for seven days, a far greater number of secondary metabolites were generated (67% of clinically identified secondary metabolites versus 25-38% using the other tested methods).

In a study with Prizer, HepatoPac consistently produced more metabolites than microsomes, S9 fractions, and suspension hepatocytes
HepatoPac co-cultures were incubated in serum-free media and exposed to each of the 27 compounds for seven days. Culture supernatant was sampled on days 2 and 7 and kept at -80°C. HPLC-tandem mass spectrometry analysis was conducted on the supernatants to identify the metabolites. The metabolite profiles generated using HepatoPac were compared with those generated using liver microsomes, liver S-9 fractions, and human hepatocyte suspension cultures.

 

Technical Resources

Type Title
Case Study Ability of a Micropatterned Hepatocyte Co-culture System to Generate Major Human Drug Metabolites
Publication Assessment of MicroPatterned Hepatocyte Co-culture System to Generate Metabolites. Drug Metab and Dispos.., 38(10), p 1900-1905 (2010).
Poster In Vitro Species Comparison Using Long-Term Hepatocyte Co-Cultures Model and Highly Sensitive UHPLC-QTOF-MS with SWATH Analysis.