2023 ACCP Webinar: From Exogenous Probes to Endogenous Biomarkers: A Paradigm Shift in the Approach to Assess Transporter Mediated Drug-Drug Interactions - ON DEMAND

Why is this Webinar important to you?

Membrane bound drug transporters, expressed in various tissues throughout the body, control the movement of endogenous and exogenous substances in and out of cells at various sites in the body.  Some drugs interact with transporters either as substrates or modulators (inhibitors or inducers), therefore, evaluation of transporter mediated drug-drug interactions (DDI) during drug development and post-approval is important to formulate clinical management strategies and ensure the safe and effective use of concomitantly administered drugs.  

 An integral part of a comprehensive clinical pharmacology program includes assessing the effect of an investigational drug on various transporters.  This assessment may be completed by either conducting several DDI trials (generally a trial for each transporter modulated by the investigational drug) or by conducting one trial to explore the effect of the investigational drug on the pharmacokinetics of several simultaneously administered (at therapeutic dose or microdose) probe drugs (“probe cocktail” approach). 

 More recently, the idea of assessing changes in the concentration of endogenous biomarkers (which are substrates of clinically relevant transporters) to gain insight on the potential of a drug to inhibit transporter activity has received widespread attention. Numerous publications and presentations by various investigators have highlighted how endogenous biomarkers can enable early “derisking” by assessing DDI potential over a wide range of inhibitor exposures, facilitate quantitative prediction of DDIs and provide mechanistic insights into observed DDIs. 

Target Audience

Physicians, Pharmacists, PhDs and other healthcare professionals interested in the evaluation of transporter-mediated DDIs during drug development and post-approval.

Learning Objectives

After completing this activity, the learner will be able to:

1. Learn how the transporter only probe cocktail trial approach has been used in drug development;
2. Explain the advantages and challenges of using microdose trials for assessment of transporter-mediated DDIs;
3. Describe the emerging role of endogenous biomarkers in the assessment of transporter-mediated DDIs;
4. Discuss how the assessment of endogenous biomarkers can be integrated in probe cocktail trials for comprehensive characterization of transporter-mediated DDI assessments.