Natural Product-Drug Interactions: Case Studies from the NaPDI Center

Date: October 25 2017
Presenter(s): Dr. Mary F. Paine


Mary F. Paine, RPh, PhD, Associate Professor, Department of Pharmaceutical Sciences, College of Pharmacy, Washington State University, Spokane, WA


Many patient groups, including those afflicted with cancer, cardiovascular disease, hepatitis C, and HIV/AIDS, often supplement their prescribed pharmacotherapeutic regimens with herbal and other natural products (NPs), raising concern for adverse interactions. As with drug-drug interactions, the most common pharmacokinetic mechanisms underlying NP-drug interactions include induction and inhibition of drug metabolizing enzymes and transporters. However, unlike for drug-drug interactions, harmonized guidelines for assessing the risk of NP-drug interactions do not exist. Because NPs are inherently complex mixtures that vary substantively in bioactive constituent composition, both between brands and between batches of the same brand, a multidisciplinary effort involving clinical pharmacologists, natural products chemists, and health informaticists is needed for rigorous assessment of the drug interaction liability of NPs. The NIH-funded Center of Excellence for Natural Product-Drug Interaction (NaPDI) Research was created in September, 2015. The mission of the NaPDI Center is to provide leadership in the identification, evaluation, and dissemination of potential clinically significant pharmacokinetic NP-drug interactions. One over-arching goal of the Center is to develop a set of Recommended Approaches to guide researchers in the proper conduct of NP-drug interaction studies; they are anticipated to evolve over time as new technologies and research data emerge. These Recommended Approaches will be based on results generated from a series of Interaction Projects that will examine four carefully selected NPs as precipitants of metabolism- and/or transporter-mediated interactions with clinically relevant object drugs. Three of these NPs – green tea, goldenseal, and cannabinoids – have been advanced to Interaction Projects that include human mechanistic in vitro studies, physiologically-based pharmacokinetic modeling and simulation, and clinical studies. The green tea project is near completion, and the goldenseal and cannabinoids projects are in progress. Key data generated from the Interaction Projects will continue to be entered into a data repository, which will be disseminated to researchers via a public access portal. Collectively, the efforts of the NaPDI Center are expected to lead to improved design of future NP-drug interaction research and ultimately, improved decisions regarding the optimal management of clinically relevant interactions.

About the presenter:

PAINE Mary, RPh, PhD

Professor, Department of Pharmaceutical Sciences, Washington State University, Spokane, USA


Mary Paine, RPh, PhD is a professor in the Department of Pharmaceutical Sciences, College of Pharmacy and Pharmaceutical Sciences, Washington State University. She received her BS in pharmacy at Oregon State University, her PhD in pharmaceutics at the University of Washington, and completed a post-doctoral fellowship in clinical pharmacology at the University of Michigan. Her longstanding research program, funded by the National Institutes of Health, focuses on adverse drug interactions precipitated by botanical and other natural products. Dr. Paine leads the Center of Excellence for Natural Product Drug Interaction Research, a multidisciplinary effort comprising clinical pharmacologists, natural products chemists, bioinformaticists, and health communications experts to provide leadership and guidance on the study and dissemination of these complex interactions. She has coauthored more than 95 publications as original research articles, reviews, editorials, and book chapters. She has served as associate editor for the journal Clinical Pharmacology and Therapeutics and is currently serving her second term as associate editor for the journal Drug Metabolism and Disposition.