ABSTRACT
Several patient groups, particularly those with chronic illnesses such as cancer, cardio?vascular disease, hepatitis C, and HIV/AIDS, often supplement their pharmacotherapeutic regimens with botanical natural products (NPs), raising concern for adverse NP-drug interactions. Like drug-drug interactions, common mechanisms underlying pharmacokinetic NP-drug interactions include induction and inhibition of drug metabolizing enzymes and transporters, leading toaltered systemic drug concen?trations and potentially, suboptimal therapeutic effects. However, unlike for drug-drug interactions, rigorous guidelines for assessing the risk of NP-drug interactions are non-existent. Establishing such guidelines for NP-drug interactions poses challenges beyond those for drug-drug interactions because NPs are inherently complex mixtures that vary substantially in phytochemical composition. The National Center for Complementary and Integrative Health created the Center of Excellence for Natural Product-Drug Interaction (NaPDI) Research in September, 2015. The mission of the NaPDI Center is to provide leadership in the identification, evaluation, and dissemination of potential clinically significant pharmaco?kinetic NP-drug interactions. A key deliverable of the Center is a set of Recommended Approaches to guide researchers in the proper conduct of NP- drug interaction studies. These approaches will be based on results generated from a series of Interaction Projects that will examine four methodically 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 pharmacoki?netic modeling and simulation, and clinical studies. Key data generated from the Interaction Projects are being entered into a data repository, which will be disseminated to researchers via a public access portal. Collectively, the efforts of the NaPDI Center should lead to improved design of future NP-drug interaction research and ultimately, improved decisions on the optimal management of clinically relevant interactions.