title: Assessing Natural Product-Drug Interactions: An End-to-End Safety Framework.
abstract: The use of natural products (NPs), including herbal medicines and other dietary supplements, by North Americans continues to increase across all age groups. This population has access to conventional medications, with significant polypharmacy observed in older adults. Thus, the safety of the interactions between multi-ingredient NPs and drugs is a topic of paramount importance. Considerations such as history of safe use, literature data from animal toxicity and human clinical studies, and NP constituent characterization would provide guidance on whether to assess NP-drug interactions experimentally. The literature is replete with reports of various NP extracts and constituents as potent inhibitors of drug metabolizing enzymes, and transporters. However, without standard methods for NP characterization or in vitro testing, extrapolating these reports to clinically-relevant NP-drug interactions is difficult. This lack of a clear definition of risk precludes clinicians and consumers from making informed decisions about the safety of taking NPs with conventional medications. A framework is needed that describes an integrated robust approach for assessing NP-drug interactions; and, translation of the data into formulation alterations, dose adjustment, labelling, and/or post-marketing surveillance strategies. A session was held at the 41st Annual Summer Meeting of the Toxicology Forum in Colorado Springs, CO, to highlight the challenges and critical components that should be included in a framework approach.
authors.affiliation: Product Safety & Regulatory Affairs, The Procter & Gamble Company, Cincinnati, OH 45040, United States. Electronic address: roe.al@pg.com.
authors.forename: Amy L
authors.initials: AL
authors.lastname: Roe
authors.affiliation: Experimental and Systems Pharmacology, College of Pharmacy, Washington State University, Spokane, WA 99210, United States. Electronic address: mary.paine@wsu.edu.
authors.forename: Mary F
authors.initials: MF
authors.lastname: Paine
authors.affiliation: College of Pharmacy, University of Arkansas for Medical Sciences, Little Rock, AR 72205, United States. Electronic address: GurleyBilyJ@uams.edu.
authors.forename: Bill J
authors.initials: BJ
authors.lastname: Gurley
authors.affiliation: Qualyst Transporter Solutions, Durham, NC 27713, United States. Electronic address: kennethbrouwer@qualyst.com.
authors.forename: Kenneth R
authors.initials: KR
authors.lastname: Brouwer
authors.affiliation: Marketed Biologicals, Biotechnology and Natural Health Products Bureau, Marketed Health Products Directorate, Health Canada, Ottawa, Ontario, Canada. Electronic address: ScottJordan@hc-sc.gc.ca.
authors.forename: Scott
authors.initials: S
authors.lastname: Jordan
authors.affiliation: Council for Responsible Nutrition, Washington, DC 20036, United States. Electronic address: JGriffiths@crnusa.org.
authors.forename: James C
authors.initials: JC
authors.lastname: Griffiths
mesh_terms: D000818:Animals; D001681:Biological Assay; D001711:Biotransformation; D019587:Dietary Supplements / Q000009:adverse effects* / Q000592:standards; D004305:Dose-Response Relationship, Drug; D064420:Drug-Related Side Effects and Adverse Reactions; D041743:Herb-Drug Interactions; D006801:Humans; D060735:Pharmacovigilance; D028321:Plant Preparations / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics / Q000592:standards; D019338:Polypharmacy; D011786:Quality Control; D018570:Risk Assessment; D018675:Toxicity Tests / Q000379:methods* / Q000592:standards
chemical_list: D028321:Plant Preparations
keywords: Cytochrome P450; Dietary supplements; Drug interactions; Herbal medicines; Metabolic enzymes; Natural products; Transporters