A New Data Repository for Pharmacokinetic Natural Product-Drug Interactions: From Chemical Characterization to Clinical Studies

Abstract

There are many gaps in scientific knowledge about the clinical significance of pharmacokinetic natural product-drug interactions (NPDIs) in which the natural product (NP) is the precipitant and a conventional drug is the object. The National Center for Complimentary and Integrative Health created the Center of Excellence for NPDI Research (NaPDI Center) (www.napdi.org) to provide leadership and guidance on the study of pharmacokinetic NPDIs. A key contribution of the Center is the first user-friendly online repository that stores and links pharmacokinetic NPDI data across chemical characterization, metabolomics analyses, and pharmacokinetic in vitro and clinical experiments (repo.napdi.org). The design is expected to help researchers more easily arrive at a complete understanding of pharmacokinetic NPDI research on a particular NP. The repository will also facilitate multidisciplinary collaborations, as the repository links all of the experimental data for a given NP across the study types. The current work describes the design of the repository, standard operating procedures used to enter data, and pharmacokinetic NPDI data that have been entered to date. To illustrate the usefulness of the NaPDI Center repository, more details on two high-priority NPs, cannabis and kratom, are provided as case studies. SIGNIFICANCE STATEMENT The data and knowledge resulting from natural product-drug interaction (NPDI) studies is distributed across a variety of information sources, rendering difficulties to find, access, and reuse. The Center of Excellence for NPDI Research addressed these difficulties by developing the first user-friendly online repository that stores data from in vitro and clinical pharmacokinetic NPDI experiments and links them with study data from chemical characterization and metabolomics analyses of natural products that are also stored in the repository.

Clinical Pharmacokinetic Assessment of Kratom (Mitragyna speciosa), a Botanical Product with Opioid-like Effects, in Healthy Adult Participants

“…Fifty commercial kratom products were sourced from various vendors throughout the United States, and their chemical compositions were compared using untargeted mass spectrometry-based metabolomics [ 6 , 7 ]. Data from the metabolomics study are freely accessible in the Center of Excellence for Natural Product Drug Interaction Research data repository ( , accessed on 9 January 2022) [ 21 ]. A representative product (described by the manufacturer as yellow Indonesian Micro Powder) was verified to be Mitragyna speciosa based on its secondary metabolite profile and DNA barcoding [ 6 ].…”

Assessing Transporter‐Mediated Natural Product‐Drug Interactions Via In vitro‐In Vivo Extrapolation: Clinical Evaluation With a Probe Cocktail

“…Composite scores analysis was used to compare the chemical composition of all 35 commercial H. canadensis samples, and GS‐16 (dried H. canadensis root material) was chosen based on its similarity to reference standards and other commercially available goldenseal supplements 19 . LC‐MS data comparing GS‐16 to other commercial goldenseal products are freely accessible in the Center of Excellence for Natural Product Drug Interaction Research data repository 20 …”

Co‐consuming green tea with raloxifene decreases raloxifene systemic exposure in healthy adult participants

“…T21 closely matched the chemical composition of the National Institutes of Standards and Technology reference material 17 . The data comparing T21 with the other green tea products are freely accessible in the Center of Excellence for Natural Product Drug Interaction Research database 19,20 …”