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.
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