Introducing Rat HepatoPac - a next generation in vitro rat micro-liver technology. Rat HepatoPac co-cultures contain primary rat hepatocytes organized into colonies of prescribed, optimized dimensions and surrounded by supportive, non-parenchymal cells which maintain in vitro functionality for over 4 weeks. This extended longevity allows for long term, low-dose toxicity testing as well as assessment of intrinsic clearance and metabolite profiles of low turnover compounds. All Hepregen DMPK and Toxicology Services can be performed using Rat HepatoPac.
Rat HepatoPac Co-cultures:
- Retain viability for over 4 weeks in vitro
- Enable evaluation of low clearance compounds
- Allow chronic toxicity studies
- Combine with Human HepatoPac to identify species-specific toxicity
Rat HepatoPac™ Characterization
Rat HepatoPac provides highly functional enzyme activity of Phase I & Phase II enzymes as well as consistent morphology and functional readouts such as albumin secretion for over 4 weeks. Data is presented summarizing the morphology, functional readouts and the activity profiles of various rat CYPs in Rat HepatoPac co-cultures for over 32 days. Rat HepatoPac remains viable and highly functional for 4 weeks rather than several days observed using conventional hepatocyte cultures.
Phase I CYP Activity
Phase II Enzyme Activity
Activity Profile Substrate Usage
References for rat specific probe substrates:
1. Madan et al. (1998) Effect of cryopreservation on cytochrome P-450 enzyme induction in cultured rat hepatocytes. DMD; Vol. 27, No. 3 (327-335).
2. Kobayashi et al. (2002) Substrate specificity for rat cytochrome P450 (CYP) isoforms: screening with cDNA-expressed systems of the rat Biochemical Pharmacology; (889-896).
3. Burke et al. (1994) Cytochrome P450 specificities of alkoxyresorufin o-dealkylation in human and rat liver. Biochemical Pharmacology; Vol. 48, No. 5 (923-936).
Improved Toxicity Testing using Rat HepatoPac
Use of in vitro rat liver cell cultures are important tools in detecting drugs associated with hepatic adverse drug reactions in preclinical development. Animal-based in vitro assays are necessary as they allow correlation of in vitro metabolic stability and metabolic profiles with in vivo metabolism studies. Unlike Rat HepatoPac which is viable for weeks in culture, alternative model systems such as rat primary hepatocyte monocultures, hepatocyte suspensions and sandwich cultures lose functionality (i.e. drug metabolizing enzyme activity) within a few days. Thus, Rat HepatoPac enables unique opportunities for improved toxicology testing including chronic and low-dose studies. Additionally, Rat HepatoPac co-cultures are micropatterned on industry-standard multiwell plates for streamlined, higher throughput in vitro assays.
HepatoPac for the Prediction of DILI
Poster - Assessment of HepatoPac to Detect Compounds that Cause Drug Induced Liver Injury in HumansRead More