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Translational Clinical Pharmacology
Symposia

Symposium 14: At the Precipice of Induction-based Drug-Drug Interactions: An Opportunity to Define the Path Forward

Tuesday, September 10, 2024
10:00 AM – 11:30 AM ET
Location:Grand Ballroom A-C
CE: 1.5

Target Audience:

The target audience for this Symposium is industry, academia and regulatory scientists in clinical pharmacology area, clinicians and others who are interested in patient-centered drug development and healthcare delivery.



Description:

Drug-drug interactions (DDIs) are a concern with polypharmacy. Coadministration of drugs that are inducers of metabolic enzymes and/or drug transporters (as precipitant) can decrease the concentrations of comedications (substrate or object) leading to reduced efficacy. Thus, it is critical to characterize the induction potential of investigational drugs during development to better inform healthcare providers on the risk of DDIs and recommend clinical interventions to ensure their effective use. Historically, clinical induction based DDIs for CYP3A substrates was conducted using rifampin, a strong prototype inducer, however its use is currently precluded due to unresolved nitrosamine impurities which pose a carcinogenesis risk. Alternative strong inducers, including carbamazepine and phenytoin, have been proposed in the interim, however due to adverse events there are concerns with administering these to healthy subjects. The challenge to apply the traditional paradigm allows for evaluation of new approaches. The goal of this section is to foster discussion on the best strategy to evaluate induction-mediated DDIs by inviting experts from relevant stakeholders to 1) discuss the applicability of an alternative approach to conduct clinical studies with moderate inducers of CYP3A instead of strong inducers; 2) explore the utility and limitation of physiologically-based pharmacokinetic (PBPK) modeling to predict the effects of inducers; 3) discuss the strategy for scenarios where the affected drug is mainly metabolized by non-CYP3A enzymes.

Goals & Objectives:

Following the completion of this activity, the learner will be able to:
  • Discuss the significant influence on efficacy of drugs by induction-mediated DDIs;
  • Discuss the optimal strategy to evaluate the impact of inducers on investigational drugs during development, considering the current restriction on use of rifampin;
  • Explain the utility and limitation of different alternative approaches including physiologically-based pharmacokinetic modeling.

Presentations:

  • Rethink the Current Practice of DDI Evaluation: Shift from Strong to Moderate Inducers

    Co-Chair & Faculty: Xinning Yang, PhD (he/him/his) – US Food & Drug Administration

  • Application of PBPK Modeling to Predict Induction-mediated DDIs

    Faculty: Tamara D. Cabalu, PhD – Merck & Co Inc

  • Beyond CYP3A: Knowledge & Gap for Induction of Non-CYP3A Metabolic Enzymes

    Co-Chair & Faculty: Diane Ramsden, BSc (she/her/hers) – Korrobio Inc

  • Discussion, Questions & Answers, Learner Feedback & Evaluations