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Research ArticleMinireview

Pharmacokinetic Interactions between Drugs and Botanical Dietary Supplements

Alyssa A. Sprouse and Richard B. van Breemen
Drug Metabolism and Disposition February 2016, 44 (2) 162-171; DOI: https://doi.org/10.1124/dmd.115.066902
Alyssa A. Sprouse
University of Illinois at Chicago/National Institutes of Health Center for Botanical Dietary Supplements Research, Department of Medicinal Chemistry and Pharmacognosy, University of Illinois, Chicago, Illinois
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Richard B. van Breemen
University of Illinois at Chicago/National Institutes of Health Center for Botanical Dietary Supplements Research, Department of Medicinal Chemistry and Pharmacognosy, University of Illinois, Chicago, Illinois
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Abstract

The use of botanical dietary supplements has grown steadily over the last 20 years despite incomplete information regarding active constituents, mechanisms of action, efficacy, and safety. An important but underinvestigated safety concern is the potential for popular botanical dietary supplements to interfere with the absorption, transport, and/or metabolism of pharmaceutical agents. Clinical trials of drug–botanical interactions are the gold standard and are usually carried out only when indicated by unexpected consumer side effects or, preferably, by predictive preclinical studies. For example, phase 1 clinical trials have confirmed preclinical studies and clinical case reports that St. John’s wort (Hypericum perforatum) induces CYP3A4/CYP3A5. However, clinical studies of most botanicals that were predicted to interact with drugs have shown no clinically significant effects. For example, clinical trials did not substantiate preclinical predictions that milk thistle (Silybum marianum) would inhibit CYP1A2, CYP2C9, CYP2D6, CYP2E1, and/or CYP3A4. Here, we highlight discrepancies between preclinical and clinical data concerning drug–botanical interactions and critically evaluate why some preclinical models perform better than others in predicting the potential for drug–botanical interactions. Gaps in knowledge are also highlighted for the potential of some popular botanical dietary supplements to interact with therapeutic agents with respect to absorption, transport, and metabolism.

Footnotes

    • Received August 20, 2015.
    • Accepted October 2, 2015.
  • This research was supported by the National Institutes of Health National Center for Complementary and Integrative Health and the Office of Dietary Supplements [Grant P50-AT000155] and the Office of the Director [Grant T32-AT007533].

  • dx.doi.org/10.1124/dmd.115.066902.

  • Copyright © 2016 by The American Society for Pharmacology and Experimental Therapeutics
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Drug Metabolism and Disposition: 44 (2)
Drug Metabolism and Disposition
Vol. 44, Issue 2
1 Feb 2016
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Research ArticleMinireview

Drug–Botanical Dietary Supplement PK Interactions

Alyssa A. Sprouse and Richard B. van Breemen
Drug Metabolism and Disposition February 1, 2016, 44 (2) 162-171; DOI: https://doi.org/10.1124/dmd.115.066902

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Research ArticleMinireview

Drug–Botanical Dietary Supplement PK Interactions

Alyssa A. Sprouse and Richard B. van Breemen
Drug Metabolism and Disposition February 1, 2016, 44 (2) 162-171; DOI: https://doi.org/10.1124/dmd.115.066902
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