Drug Metabolism Services

Description

Using HepatoPac® micropatterned co-cultures (MPCCs) of primary hepatocytes and stromal cells, SOLVO metabolism assays investigate the in vitro metabolism properties of your molecule across multiple species (human, monkey, dog and rat). MPCCs are provided in collaboration with Ascendance Biotechnology, Inc. (Medford, MA), and have been shown to exhibit superior metabolising capability, and prediction of intrinsic clearance compared to other in vitro methods 1–3. Our highly trained bioanalysts using our suite of state of the art LC-MS/MS equipment can assess metabolic stability and provide preliminary metabolite identification (both primary and secondary) and quantitation across multiple species for your molecule.

SOLVO MPCC assays are configured in 24 or 96 well formats and can be configured to produce data on
• metabolic stability
• metabolic profile and identification

MPCCs offer the following advantages over traditional drug metabolism tools:
• Stable expression of DMEs (Phase 1 and Phase 2) and uptake and efflux transporters for an extended period (>7 days), compared to plated or suspension hepatocytes.
• Greater range and extent of metabolism, particularly for slowly metabolized molecules.
• Enhanced prediction of in vivo clearance for molecules with low CLint

References:

1. Dalvie, D. et al. Assessment of three human in vitro systems in the generation of major human excretory and circulating metabolites. Chem. Res. Toxicol. 22, 357–68 (2009).
2. Chan, T. S., Yu, H., Moore, A., Khetani, S. R. & Tweedie, D. Meeting the Challenge of Predicting Hepatic Clearance of Compounds Slowly Metabolized by Cytochrome P450 Using a Novel Hepatocyte Model, HepatoPac. Drug Metab. Dispos. 41, 2024–2032 (2013).
3. Lin, C., Shi, J., Moore, A. & Khetani, S. R. Prediction of Drug Clearance and Drug-Drug Interactions in Microscale Cultures of Human Hepatocytes. Drug Metab. Dispos. 44, 127–36 (2016).