Several patient groups,particularly those with chronic illnesses such as cancer,cardiovascular 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 concentrations 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(Na PDI)Research in September,2015.The mission of the Na PDI Center is to provide leadership in the identification,evaluation,and dissemination of potential clinically significant pharmacokinetic 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 pharmacokinetic 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 Na PDI Center should lead to improved design of future NP-drug interaction research and ultimately,improved decisions on the optimal management of clinically relevant interactions. Several patient groups, particularly those with chronic illnesses such as cancer, cardiovascular disease, hepatitis C, and HIV / AIDS, often supplement their pharmacotherapeutic regimens with botanical natural products (NPs), raising concern for adverse NP-drug interactions. interactions, common mechanisms underlying pharmacokinetic NP-drug interactions include induction and inhibition of drug metabolizing enzymes and transporters, leading toaltered systemic drug concentrations and potentially, potentially suboptimal therapeutic effects. Still, 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 vary in phytochemical composition. The National Center for Complementary and Integrative Health created the Center of Excellence for Natural Product-Drug Interaction (Na PDI) Research in September, 2015. The mission of the Na PDI Center is to provide leadership in the identification, evaluation, and dissemination of potentially clinically significant pharmacokinetic 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. The 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 pharmacokinetic 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 Na PDI Center should lead to improved design of future NP-drug interaction research and ultimately, improved decisions on the optimal management of clinically relevant interactions.