Probe Cocktail Studies

The conduct of drug interaction studies was revolutionized by the ability to evaluate more than one potential drug-drug interaction (DDI) within a single study. Cocktail studies provide a means to screen for DDIs through multiple metabolic pathways within a single study. Usually conducted in healthy volunteers, these studies use concurrent administration of probe substrates and assessment of biomarkers to simultaneously assess drug-metabolizing enzyme (DME) activities before (baseline) and during drug treatment. Evaluation of DME can be for effect of a drug on constitutive DME (i.e., inhibition, induction, or activation) or to evaluate the effect of an inhibitor, inducer, or activator on the pharmacokinetics and pharmacodynamics of the DME pathway of the drug in question. Studies should be designed with the use of safe, validated probes and published, validated cocktails. Advantages of using cocktail studies in drug development include reduced subject variability (because the same subjects are used for each phase of the study), increased efficiency, and lower costs. Potential limitations can be addressed by proper study design. Because cocktail studies assess the potential extent of DDIs, inferences for drug dosing and use may be drawn.