Reaction Phenotyping

Reaction phenotyping assays have become an integral part of drug discovery screening as tools to minimize drug–drug interaction potential and to avoid complications due to polymorphic expression of drug metabolizing enzymes.

In vitro reaction phenotyping methods enable a prediction of human pharmacokinetics and dosages and determine the significance of individual human-specific drug metabolizing enzymes.

Reaction phenotyping is very useful to predict the in vivo metabolic clearance and the contribution of individual drug metabolizing enzymes to the total in vivo clearance. A drug with a metabolic clearance (e.g. >40% of the total clearance) and metabolized by a polymorphic enzyme and/or a primary enzyme (e.g. >30-50% of the total metabolic clearance) has an increased risk of drug-drug interactions and/or individual variation.

Assay Methodology

At Quintara Discovery, we have validated assays for reaction phenotyping. The studies can be conducted in the following ways:

  • Incubation of test compounds with individual CYP450 isoforms. Currently, there are 15 metabolizing enzymes available for assay.
  • Incubation of test compound with human liver microsomes in the presence of specific inhibitors for each of the major CYP450 isoforms.