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Ex Vivo Enzyme Induction Studies

Ex Vivo cytochrome P450 (CYP) and UDP glucuronyltransferase (UGT) enzyme induction experiments in monkey, dog, rat, and mouse liver microsomes can identify the species with the closest induction profile to humans and help explain unexpected results in animal pharmacokinetic/pharmacodynamic (PK/PD), absorption, metabolism, distribution, and excretion (ADME), and toxicology studies. 

Not only are these types of induction studies cost-effective, but they can also provide critical information to your investigation, such as which prototypical CYP inducers the drug candidate resembles, which animal species most closely resembles human, and epigenetic tumor formation.

Our Approach to Ex Vivo Induction Studies

Much of our understanding of CYP induction stems from studies conducted in rodents. The design of these studies is generally applicable to other species, although some significant species differences exist, such as:

Positive Controls

Positive controls show how your compound relates to the prototypical inducers in your animal model. To achieve relevant comparisons in microsomal activity, we maintain a selection of suitable positive controls from rat, mouse, dog, and monkey for both CYPs and UGTs to match with each drug candidate. Additionally, we consult our historical control values acquired over several years to provide the highest level of confidence in our assessment of your compound.

Prototypical Inducers

  • Β-naphthoflavone
  • Phenobarbital
  • Isoniazid
  • Rifampin
  • Dexamethasone
  • Clofibric acid

Related Services: Enzyme Induction Screening

Discovery Plus™ Screening Suite presents medium-throughput alternatives to definitive metabolism & DDI studies through non-GLP, abbreviated versions of our definitive assays. This option is best used for comparison of multiple compounds (during the Lead Optimization stage) or to yield preliminary data for definitive in vitro studies.

Find out more

Dr. Joanna Barbara explains how calculations about how calculations are formulated, spent media analysis, best test systems, and TA concentrations in our 2019 webinar, “In Vitro Induction Studies: Elements of Design and Important Considerations in Data Analysis”

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Find out more about study design, results, follow-up, test systems and more in our downloadable flyer discussing contract enzyme induction and hepatotoxicity studies

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