Drug metabolism in vitro

How can you improve human hepatic drug metabolism predictions?

Drug metabolism is a complex process where drugs are structurally modified to form metabolites. Studying drug metabolism and pharmacokinetics (DMPK) is required to identify lead compounds with optimal PK/PD properties, optimize efficacy, and minimize safety issues.

Standard in vitro drug metabolism and pharmacokinetics studies face various challenges. Many are incompatible with new therapeutic modalities, are inaccurate predictors of human in vivo clearance rates, and fail to identify rare or human-specific metabolites.

Our solution

Individual Liver-, Lung-, and Gut-on-a-chip in vitro models can be used to study drug metabolism, metabolites, and transporter-mediated uptake and efflux.

Connecting two models related to DMPK offers an improved prediction of in vivo pharmacokinetics and pharmacodynamics. For example, combining gut and liver models allows orally administered drugs to be studied in a multi-organ system. The system can reflect compound permeability through an intestinal barrier, hepatic metabolism, organ–organ interaction, and crosstalk.

PhysioMimix^® Drug Metabolism Assays allow the measurement of parent and metabolite concentrations within the intracellular compartment and culture medium, to determine all standard metabolic parameters. They are particularly well suited to measuring slowly metabolized, low clearance drugs where in other systems, such as suspension hepatocytes, compound turnover is not detected.

Our organ-on-a-chip (OOC) models maintain phase I and II metabolism together with transporter function at in vivo-like levels for weeks. The ability to recirculate media around the cultures allows for the decrease in parent or build-up of metabolites to be measured and complete metabolic characterization from a single culture.