Review ArticleReview Article
Modeling Pharmacokinetic Natural Product–Drug Interactions for Decision-Making: A NaPDI Center Recommended Approach
Emily J. Cox, Dan-Dan Tian, John D. Clarke, Allan E. Rettie, Jashvant D. Unadkat, Kenneth E. Thummel, Jeannine S. McCune and Mary F. Paine
Hyunyoung Jeong, ASSOCIATE EDITOR
Pharmacological Reviews April 2021, 73 (2) 847-859; DOI: https://doi.org/10.1124/pharmrev.120.000106
Emily J. Cox
Center of Excellence for Natural Product Drug Interaction Research, Spokane, Washington (J.D.C., A.E.R., J.D.U., K.E.T., J.S.M., M.F.P.); Department of Pharmaceutical Sciences, Washington State University, Spokane, Washington (E.J.C., D.-D.T., J.D.C., M.F.P.); Departments of Medicinal Chemistry (A.E.R.) and Pharmaceutics (J.D.U., K.E.T.), University of Washington, Seattle, Washington; and Department of Population Sciences, City of Hope, Duarte, California (J.S.M.)
Dan-Dan Tian
Center of Excellence for Natural Product Drug Interaction Research, Spokane, Washington (J.D.C., A.E.R., J.D.U., K.E.T., J.S.M., M.F.P.); Department of Pharmaceutical Sciences, Washington State University, Spokane, Washington (E.J.C., D.-D.T., J.D.C., M.F.P.); Departments of Medicinal Chemistry (A.E.R.) and Pharmaceutics (J.D.U., K.E.T.), University of Washington, Seattle, Washington; and Department of Population Sciences, City of Hope, Duarte, California (J.S.M.)
John D. Clarke
Center of Excellence for Natural Product Drug Interaction Research, Spokane, Washington (J.D.C., A.E.R., J.D.U., K.E.T., J.S.M., M.F.P.); Department of Pharmaceutical Sciences, Washington State University, Spokane, Washington (E.J.C., D.-D.T., J.D.C., M.F.P.); Departments of Medicinal Chemistry (A.E.R.) and Pharmaceutics (J.D.U., K.E.T.), University of Washington, Seattle, Washington; and Department of Population Sciences, City of Hope, Duarte, California (J.S.M.)
Allan E. Rettie
Center of Excellence for Natural Product Drug Interaction Research, Spokane, Washington (J.D.C., A.E.R., J.D.U., K.E.T., J.S.M., M.F.P.); Department of Pharmaceutical Sciences, Washington State University, Spokane, Washington (E.J.C., D.-D.T., J.D.C., M.F.P.); Departments of Medicinal Chemistry (A.E.R.) and Pharmaceutics (J.D.U., K.E.T.), University of Washington, Seattle, Washington; and Department of Population Sciences, City of Hope, Duarte, California (J.S.M.)
Jashvant D. Unadkat
Center of Excellence for Natural Product Drug Interaction Research, Spokane, Washington (J.D.C., A.E.R., J.D.U., K.E.T., J.S.M., M.F.P.); Department of Pharmaceutical Sciences, Washington State University, Spokane, Washington (E.J.C., D.-D.T., J.D.C., M.F.P.); Departments of Medicinal Chemistry (A.E.R.) and Pharmaceutics (J.D.U., K.E.T.), University of Washington, Seattle, Washington; and Department of Population Sciences, City of Hope, Duarte, California (J.S.M.)
Kenneth E. Thummel
Center of Excellence for Natural Product Drug Interaction Research, Spokane, Washington (J.D.C., A.E.R., J.D.U., K.E.T., J.S.M., M.F.P.); Department of Pharmaceutical Sciences, Washington State University, Spokane, Washington (E.J.C., D.-D.T., J.D.C., M.F.P.); Departments of Medicinal Chemistry (A.E.R.) and Pharmaceutics (J.D.U., K.E.T.), University of Washington, Seattle, Washington; and Department of Population Sciences, City of Hope, Duarte, California (J.S.M.)
Jeannine S. McCune
Center of Excellence for Natural Product Drug Interaction Research, Spokane, Washington (J.D.C., A.E.R., J.D.U., K.E.T., J.S.M., M.F.P.); Department of Pharmaceutical Sciences, Washington State University, Spokane, Washington (E.J.C., D.-D.T., J.D.C., M.F.P.); Departments of Medicinal Chemistry (A.E.R.) and Pharmaceutics (J.D.U., K.E.T.), University of Washington, Seattle, Washington; and Department of Population Sciences, City of Hope, Duarte, California (J.S.M.)
Mary F. Paine
Center of Excellence for Natural Product Drug Interaction Research, Spokane, Washington (J.D.C., A.E.R., J.D.U., K.E.T., J.S.M., M.F.P.); Department of Pharmaceutical Sciences, Washington State University, Spokane, Washington (E.J.C., D.-D.T., J.D.C., M.F.P.); Departments of Medicinal Chemistry (A.E.R.) and Pharmaceutics (J.D.U., K.E.T.), University of Washington, Seattle, Washington; and Department of Population Sciences, City of Hope, Duarte, California (J.S.M.)
Hyunyoung Jeong
Roles: ASSOCIATE EDITOR

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In this issue
Review ArticleReview Article
Modeling Pharmacokinetic Natural Product–Drug Interactions
Emily J. Cox, Dan-Dan Tian, John D. Clarke, Allan E. Rettie, Jashvant D. Unadkat, Kenneth E. Thummel, Jeannine S. McCune and Mary F. Paine
Pharmacological Reviews April 1, 2021, 73 (2) 847-859; DOI: https://doi.org/10.1124/pharmrev.120.000106
Review ArticleReview Article
Modeling Pharmacokinetic Natural Product–Drug Interactions
Emily J. Cox, Dan-Dan Tian, John D. Clarke, Allan E. Rettie, Jashvant D. Unadkat, Kenneth E. Thummel, Jeannine S. McCune and Mary F. Paine
Pharmacological Reviews April 1, 2021, 73 (2) 847-859; DOI: https://doi.org/10.1124/pharmrev.120.000106
Jump to section
- Article
- Abstract
- I. Introduction: Application of Static and Dynamic Models to Natural Products
- II. Generating and Selecting Data for Static and Physiologically Based Pharmacokinetic Models
- III. Applying or Developing Static and Physiologically Based Pharmacokinetic Models
- IV. Building Physiologically Based Pharmacokinetic Models De Novo for NPDIs
- V. Using Static and Physiologically Based Pharmacokinetic Models to Prioritize Natural Product–Drug Interaction Risk
- VI. Future Research
- VII. Conclusions
- Acknowledgments
- Authorship Contributions
- Footnotes
- Abbreviations
- References
- Figures & Data
- Info & Metrics
- eLetters
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