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OtherMetabolism, Transport, and Pharmacogenetics

Refined prediction of pharmacokinetic kratom-drug interactions: time-dependent inhibition considerations

Rakshit S. Tanna, Dan-Dan Tian, Nadja B. Cech, Nicholas H. Oberlies, Allan E. Rettie, Kenneth E. Thummel and Mary F. Paine
Journal of Pharmacology and Experimental Therapeutics October 22, 2020, JPET-AR-2020-000270; DOI: https://doi.org/10.1124/jpet.120.000270
Rakshit S. Tanna
1Pharmaceutical Sciences, Washington State University, United States of America
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Dan-Dan Tian
2Washington State University, United States
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Nadja B. Cech
3United States
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Nicholas H. Oberlies
4Chemistry and Biochemistry, University of North Carolina at Greensboro, United States of America
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Allan E. Rettie
5Dept. of Medicinal Chemistry, University of Washington, United States
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Kenneth E. Thummel
6Department of Pharmaceutics, University of Washington, United States
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Mary F. Paine
1Pharmaceutical Sciences, Washington State University, United States of America
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  • For correspondence: mary.paine@wsu.edu
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      Supplementary Figure 1 -   Inhibitory effects of kratom extracts (coded K-50, K-51, and K-52) and mitragynine on
      cytochrome P450 (CYP) 2C9 (diclofenac 4′-hydroxylation) (A), CYP2D6 (dextromethorphan Odemethylation) (B), and CYP3A (midazolam 1′-hydroxylation) (C) activities in HLMs and CYP3A (D) activity in HIMs. Extracts were tested at 2, 10, and 20 µg/mL; mitragynine was tested at 1, 10, and 100 µM. Positive control inhibitors included sulfaphenazole (1 µM), quinidine (2 µM), and ketoconazole (0.1 µM) for CYP2C9, CYP2D6, and CYP3A, respectively.

      Supplementary Figure 2 - Representative Lineweaver–Burk plot showing inhibition of CYP2D6-mediated
      dextromethorphan O-demethylation by mitragynine (0.37-10 µM) in HLMs.

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Journal of Pharmacology and Experimental Therapeutics: 385 (3)
Journal of Pharmacology and Experimental Therapeutics
Vol. 385, Issue 3
1 Jun 2023
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OtherMetabolism, Transport, and Pharmacogenetics

Refined prediction of potential kratom-drug interactions

Rakshit S. Tanna, Dan-Dan Tian, Nadja B. Cech, Nicholas H. Oberlies, Allan E. Rettie, Kenneth E. Thummel and Mary F. Paine
Journal of Pharmacology and Experimental Therapeutics October 22, 2020, JPET-AR-2020-000270; DOI: https://doi.org/10.1124/jpet.120.000270

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OtherMetabolism, Transport, and Pharmacogenetics

Refined prediction of potential kratom-drug interactions

Rakshit S. Tanna, Dan-Dan Tian, Nadja B. Cech, Nicholas H. Oberlies, Allan E. Rettie, Kenneth E. Thummel and Mary F. Paine
Journal of Pharmacology and Experimental Therapeutics October 22, 2020, JPET-AR-2020-000270; DOI: https://doi.org/10.1124/jpet.120.000270
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