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Research ArticlePerspective

Herb–Drug Interactions: Challenges and Opportunities for Improved Predictions

Scott J. Brantley, Aneesh A. Argikar, Yvonne S. Lin, Swati Nagar and Mary F. Paine
Drug Metabolism and Disposition March 2014, 42 (3) 301-317; DOI: https://doi.org/10.1124/dmd.113.055236
Scott J. Brantley
Division of Pharmacotherapy and Experimental Therapeutics, UNC Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, North Carolina (S.J.B.); Department of Pharmaceutical Sciences, Temple University School of Pharmacy, Philadelphia, Pennsylvania (A.A.A., S.N.); Department of Pharmaceutics, University of Washington, Seattle, Washington (Y.S.L.); and College of Pharmacy, Washington State University, Spokane, Washington (M.F.P.)
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Aneesh A. Argikar
Division of Pharmacotherapy and Experimental Therapeutics, UNC Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, North Carolina (S.J.B.); Department of Pharmaceutical Sciences, Temple University School of Pharmacy, Philadelphia, Pennsylvania (A.A.A., S.N.); Department of Pharmaceutics, University of Washington, Seattle, Washington (Y.S.L.); and College of Pharmacy, Washington State University, Spokane, Washington (M.F.P.)
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Yvonne S. Lin
Division of Pharmacotherapy and Experimental Therapeutics, UNC Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, North Carolina (S.J.B.); Department of Pharmaceutical Sciences, Temple University School of Pharmacy, Philadelphia, Pennsylvania (A.A.A., S.N.); Department of Pharmaceutics, University of Washington, Seattle, Washington (Y.S.L.); and College of Pharmacy, Washington State University, Spokane, Washington (M.F.P.)
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Swati Nagar
Division of Pharmacotherapy and Experimental Therapeutics, UNC Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, North Carolina (S.J.B.); Department of Pharmaceutical Sciences, Temple University School of Pharmacy, Philadelphia, Pennsylvania (A.A.A., S.N.); Department of Pharmaceutics, University of Washington, Seattle, Washington (Y.S.L.); and College of Pharmacy, Washington State University, Spokane, Washington (M.F.P.)
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Mary F. Paine
Division of Pharmacotherapy and Experimental Therapeutics, UNC Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, North Carolina (S.J.B.); Department of Pharmaceutical Sciences, Temple University School of Pharmacy, Philadelphia, Pennsylvania (A.A.A., S.N.); Department of Pharmaceutics, University of Washington, Seattle, Washington (Y.S.L.); and College of Pharmacy, Washington State University, Spokane, Washington (M.F.P.)
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Abstract

Supported by a usage history that predates written records and the perception that “natural” ensures safety, herbal products have increasingly been incorporated into Western health care. Consumers often self-administer these products concomitantly with conventional medications without informing their health care provider(s). Such herb–drug combinations can produce untoward effects when the herbal product perturbs the activity of drug metabolizing enzymes and/or transporters. Despite increasing recognition of these types of herb–drug interactions, a standard system for interaction prediction and evaluation is nonexistent. Consequently, the mechanisms underlying herb–drug interactions remain an understudied area of pharmacotherapy. Evaluation of herbal product interaction liability is challenging due to variability in herbal product composition, uncertainty of the causative constituents, and often scant knowledge of causative constituent pharmacokinetics. These limitations are confounded further by the varying perspectives concerning herbal product regulation. Systematic evaluation of herbal product drug interaction liability, as is routine for new drugs under development, necessitates identifying individual constituents from herbal products and characterizing the interaction potential of such constituents. Integration of this information into in silico models that estimate the pharmacokinetics of individual constituents should facilitate prospective identification of herb–drug interactions. These concepts are highlighted with the exemplar herbal products milk thistle and resveratrol. Implementation of this methodology should help provide definitive information to both consumers and clinicians about the risk of adding herbal products to conventional pharmacotherapeutic regimens.

Footnotes

    • Received October 4, 2013.
    • Accepted December 11, 2013.
  • dx.doi.org/10.1124/dmd.113.055236.

  • This research was supported in part by the National Institutes of Health National Institute of General Medical Sciences [Grant R01-GM077482] and the National Institutes of Health National Cancer Institute [Grant R03-CA159389]. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

  • Copyright © 2014 by The American Society for Pharmacology and Experimental Therapeutics
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Drug Metabolism and Disposition: 42 (3)
Drug Metabolism and Disposition
Vol. 42, Issue 3
1 Mar 2014
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Research ArticlePerspective

Challenges and Opportunities for Improved HDI Predictions

Scott J. Brantley, Aneesh A. Argikar, Yvonne S. Lin, Swati Nagar and Mary F. Paine
Drug Metabolism and Disposition March 1, 2014, 42 (3) 301-317; DOI: https://doi.org/10.1124/dmd.113.055236

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Research ArticlePerspective

Challenges and Opportunities for Improved HDI Predictions

Scott J. Brantley, Aneesh A. Argikar, Yvonne S. Lin, Swati Nagar and Mary F. Paine
Drug Metabolism and Disposition March 1, 2014, 42 (3) 301-317; DOI: https://doi.org/10.1124/dmd.113.055236
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  • Article
    • Abstract
    • Introduction
    • Biochemical Mechanisms Underlying Pharmacokinetic HDIs
    • Challenges with Evaluating and Predicting PK HDIs
    • Regulatory Perspectives on Herbal Products
    • HDI Predictions
    • Case Study: Milk Thistle
    • Case Study: Resveratrol
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