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Probe Cocktail Studies

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Drug Interactions in Infectious Diseases

Part of the book series: Infectious Disease ((ID))

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Abstract

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 or to evaluate the effect of an inhibitor or inducer 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, 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.

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Abbreviations

AUC:

Area under the concentration time curve

CI:

Confidence intervals

Cmax :

Maximum concentration

CYP:

Cytochrome P450

DDI:

Drug-drug interaction

DME:

Drug metabolizing enzymes

EM:

Extensive metabolizer

EMA:

European Medicines Agency

FDA:

U.S. Food and Drug Administration

NAT2:

N-acetyltransferase 2

PhRMA:

Pharmaceutical Research and Manufacturers of America

PM:

Poor metabolizer

UM:

Ultra-rapid metabolizer

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Authors and Affiliations

  1. Bertino Consulting, 3078 New Williamsburg Drive, Schenectady, 12303, NY, USA

    Anne N. Nafziger

  2. School of Pharmacy & Pharmaceutical Sciences, Department of Pharmacy Practice, University at Buffalo, State University of New York, Buffalo, NY, USA

    Anne N. Nafziger

  3. Bertino Consulting, Schenectady, NY, USA

    Joseph S. Bertino Jr. (Principal)

  4. College of Physicians & Surgeons, Columbia University, New York, NY, USA

    Joseph S. Bertino Jr. (Associate Professor of Pharmacology)

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  1. Anne N. Nafziger
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  2. Joseph S. Bertino Jr.
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  3. Joseph S. Bertino Jr.
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Correspondence to Anne N. Nafziger .

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Editors and Affiliations

  1. , Infectious Diseases, GlaxoSmithKline, Research Triangle Park, 27709, North Carolina, USA

    Stephen C. Piscitelli

  2. College of Pharmacy, Dept. Pharmacy Practice, University of Illinois, Chicago, Chicago, 60612-7230, Illinois, USA

    Keith A. Rodvold

  3. , Pharmaceutical Sciences, Albany College of Pharmacy, Albany, 12208, New York, USA

    Manjunath P. Pai

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Nafziger, A.N., Bertino, J.S., Bertino, J.S. (2011). Probe Cocktail Studies. In: Piscitelli, S., Rodvold, K., Pai, M. (eds) Drug Interactions in Infectious Diseases. Infectious Disease. Humana Press. https://doi.org/10.1007/978-1-61779-213-7_19

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