Selection of Priority Natural Products for Evaluation as Potential Precipitants of Natural Product–Drug Interactions: A NaPDI Center Recommended Approach

Johnson, Eric J.; González‐Pérez, Vanessa; Tian, Dandan; Lin, Yvonne S.; Unadkat, Jashvant D.; Rettie, Allan E.; Shen, Danny D.; Paine, Mary F.

doi:10.1124/dmd.118.081273

Cited by 19 publications

(27 citation statements)

References 25 publications

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“…As with drug-drug interactions, common mechanisms underlying natural product-drug interactions include inhibition of drug metabolizing enzymes, particularly the cytochromes P450 (CYPs), by precipitant ("perpetrator") constituents in natural products (Johnson et al, 2018;Paine et al, 2018). Kratom extracts, when tested using recombinant enzymes with fluorometric or luminogenic CYP probe substrates, inhibited CYP2D6, CYP3A, and CYP1A2 activity (IC 50 : 0.64-3.6 µg/mL, 0.78-140 μg/mL, and 39 μg/mL, respectively) (Kong et al, 2011;Hanapi et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

Refined Prediction of Pharmacokinetic Kratom-Drug Interactions: Time-Dependent Inhibition Considerations

Tanna

Tian

Cech

et al. 2020

J Pharmacol Exp Ther

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Abbreviations: AUC, area under the plasma concentration-time curve; AUCR, ratio of AUC in presence to absence of inhibitor; CYP, cytochrome P450; DEA, Drug Enforcement Administration; f u,p , fraction unbound in human plasma; HIMs, human intestinal microsomes; HLMs, human liver microsomes; IVIVE, in vitro to in vivo extrapolation; k inact , maximum rate of inactivation; K I , time-dependent inhibition constant; K i , reversible inhibition constant; TDI, timedependent inhibition; UPLC-MS/MS, ultra-high performance liquid chromatography-tandem mass spectrometry This article has not been copyedited and formatted. The final version may differ from this version.

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Section: Introductionmentioning

confidence: 99%

Refined Prediction of Pharmacokinetic Kratom-Drug Interactions: Time-Dependent Inhibition Considerations

Tanna

Tian

Cech

et al. 2020

J Pharmacol Exp Ther

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“…The first charge of the NaPDI Center was to select and prioritize the NPs to be studied as potential precipitants of NPDIs. A systematic method was developed to identify four priority NPs that will serve as exemplars for the Recommended Approaches (Johnson et al, 2018). Beginning with a list of 47 commonly used NPs, these four NPs were selected based on existing in vitro and clinical data suggesting the potential to precipitate a NPDI.…”

Section: Recommended Approachesmentioning

confidence: 99%

Recommended Approaches for Pharmacokinetic Natural Product-Drug Interaction Research: a NaPDI Center Commentary

Paine

Shen

2018

Drug Metab Dispos

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Sales of botanical dietary supplements and other purported medicinal natural products (NPs) have escalated over the past ∼25 years, increasing the potential for NPs to precipitate clinically significant pharmacokinetic interactions with U.S. Food and Drug Administration-approved medications [NP-drug interactions (NPDIs)]. However, published NPDI studies to date often lack consistency in design, implementation, and documentation, which present difficulties in assessing the clinical significance of the results. Common hurdles include large variability in the admixture composition of phytoconstituents between and within batches of a given NP, limited knowledge on the pharmacokinetics of precipitant NP constituents, and use of animal and/or in vitro models which, in some cases, are not mechanistically appropriate for extrapolation to humans. The National Center for Complementary and Integrative Health created a Center of Excellence for Natural Product-Drug Interaction Research (NaPDI Center) to address these unmet research needs. The NaPDI Center has two overarching goals: 1) develop Recommended Approaches to guide researchers in the proper conduct of NPDI studies, which will evolve over time concurrent with emerging technologies and new research data, and 2) apply the Recommended Approaches in evaluating four model NPs as precipitants of NPDIs with clinically relevant object drugs. The major objectives of this commentary are to 1) explain the rationale for creating the NaPDI Center; 2) describe the decision trees developed by the NaPDI Center to enhance the planning, rigor, and consistency of NPDI studies; and 3) provide a framework for communicating results to the multidisciplinary scientists interested in the NaPDI Center's interaction projects.

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“…It provides a user-friendly interface that enables users with limited informatics skills to effectively explore relevant data (Li, 2015). As of March 2020, coverage of the repository is limited to four carefully selected high-priority NPs based on a systematic method for the purpose of demonstrating the Recommended Approaches (Johnson et al, 2018): cannabis (Cannabis sativa), goldenseal (Hydrastis canadensis), green tea (Camellia sinensis), and kratom (Mitragyna speciosa). A prior Recommended Approach (Johnson et al, 2018) reported the inclusion of licorice (Glycyrrhiza spp.).…”

Section: Introductionmentioning

confidence: 99%

“…One objective of the NaPDI Center is to develop and apply a set of Recommended Approaches to determine the clinical relevance of pharmacokinetic NPDIs ( Johnson et al, 2018 ; Paine et al, 2018 ; Kellogg et al, 2019 ). A key deliverable of the Center is the development of an online repository for data generated by the NaPDI Center ( repo.napdi.org ).…”

Section: Introductionmentioning

confidence: 99%

“…The repository combines data currently distributed across a variety of information sources into a single user-friendly format complemented by an information portal. This portal, also developed by the NaPDI Center, disseminates the Recommended Approaches ( Johnson et al, 2018 ; Paine et al, 2018 ; Kellogg et al, 2019 ) on the optimal conduct of pharmacokinetic NPDI studies ( napdicenter.org ). Combined, these new resources will help advance pharmacokinetic NPDI research by providing Recommended Approaches and novel pharmacokinetic NPDI data.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2020

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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.

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Selection of Priority Natural Products for Evaluation as Potential Precipitants of Natural Product–Drug Interactions: A NaPDI Center Recommended Approach

Cited by 19 publications

References 25 publications

Refined Prediction of Pharmacokinetic Kratom-Drug Interactions: Time-Dependent Inhibition Considerations

Refined Prediction of Pharmacokinetic Kratom-Drug Interactions: Time-Dependent Inhibition Considerations

Recommended Approaches for Pharmacokinetic Natural Product-Drug Interaction Research: a NaPDI Center Commentary

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

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