Pooled human hepatocytes are a preferred test system in many drug discovery and development applications which require intact cellular systems for in vitro testing. Intact hepatocytes contain the major hepatic drug-metabolizing enzymes and co-factors required to evaluate the metabolism and potential drug-drug interactions of drug candidates effectively.
Over the last decade, improvements of cryopreservation technologies make possible using cryopreserved human hepatocyte more conveniently. Pooled cryopreserved hepatocytes reduce the inter-individual differences and polymorphic distribution of liver enzymes. However, this is crucial to carefully select a pool according to its performance but also the application used for.
Reducing inter-individual differences with HepatoSure
This pool is characterized for 10 CYPs activities, UGT and SULT. This characterization can be found with mostly any other pool…so what’s more with HepatoSure? We have added the Aldehyde Oxidase activity, using 2 marker substrates since AO metabolism can play an extensive role in the clearance of many drugs. Intrinsic clearance values, using 5 marker substrates have been also added and finally we looked into uptake activity with 4 specific transporters.
Reducing lot-to-lot variability
Why having a large pool if we would be unable to offer lot-to-lot consistency? In the following graph we represented the activities for 4 different HepatoSure™ lots. Has shown there is minimal variability when comparing lot-to-lot. HepatoSure™ was designed for assays where continued use of historical data is desired.
HepatoSure™ is a 100-donor pool offering large perspective of offering a high number of vials. If you intend to harmonize to source a unique batch for multi-site, HepatoSure™ is probably the best solution to consider.
- Met ID
- Metabolic stability
- Drug inhibition
- Uptake assays
- Metabolism by aldehyde oxidase