Enzyme Induction Studies to Evaluate Drug-Drug Interaction Potential
Enzyme Induction studies assess the potential for a drug candidate to induce (up-regulate) the expression of drug-metabolizing enzymes, resulting in increased clearance of the drug or another metabolized compound.
Induction studies fall into two categories: in vitro and ex vivo. In vitro studies evaluate the test article for its perpetrator potential using primary cultures of hepatocytes from human and/or other species, while ex vivo 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.
Enzyme induction data is key to the evaluation of drug-drug interaction (DDI) potential of your compound.
To address direction from the Food and Drug Administration (FDA) to “determine if the investigational drug is an inducer of drug-metabolizing enzymes” (In Vitro Drug Interactions Studies— Cytochrome P450 Enzyme- and Transporter-Mediated Drug Interactions: Final Guidance for Industry, FDA 2020), we offer in vitro and ex vivo enzyme induction studies designed to meet current FDA, European Medicines Agency (EMA), and Pharmaceuticals and Medical Devices Agency (PMDA) expectations for new drug applications.
Frequently Asked Questions regarding enzyme induction study design and results
You asked, we answered.
Read our blog post or watch our webinar in which VP of Scientific Operations, Dr. Joanna Barbara, answers frequently asked questions such as “How are test article concentrations selected?” and “Why do I need to do spent media analysis?” Our experts walk you through each part of the study, reasoning for controls and study design elements, regulatory expectations, information gleaned from results, and more
Automation and Analysis
- Validated qRT-PCR methods
- Tecan liquid handling systems or manual incubations available
- Validated LC-MS/MS methods for activity endpoints
- Deuterated internal standards (all CYPs and most UGTs) for activity endpoints
- Comprehensive, publication-quality reports
Related Services: CYP 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.