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Translating Kratom-Drug Interactions: From Bedside to Bench and Back
Rakshit S Tanna1, Nadja B Cech1, Nicholas H Oberlies1
1Department of Pharmaceutical Sciences, College of Pharmacy and Pharmaceutical Sciences, Washington State University, Spokane, Washington (R.S.T., M.F.P.); Department of Chemistry and Biochemistry, University of North Carolina at Greensboro, Greensboro, North Carolina (N.B.C., N.H.O.); Center of Excellence for Natural Product Drug Interaction Research, Spokane, Washington (N.B.C., N.H.O., A.E.R., K.E.T., M.F.P.); Departments of Medicinal Chemistry (A.E.R.) and Pharmaceutics (K.E.T.), School of Pharmacy, University of Washington, Seattle, Washington.
Kratom, used for pain and opioid withdrawal, may cause harmful drug interactions. It inhibits key enzymes like CYP2D6 and CYP3A, increasing exposure to other drugs.
Area of Science:
- Pharmacology and Toxicology
- Natural Products Chemistry
Background:
- Kratom is a botanical product from the coffee family, used for pain and opioid withdrawal.
- Kratom alkaloids, like mitragynine, are found in overdose deaths, often involving multiple substances.
- Concerns exist regarding kratom's potential to cause drug interactions.
Purpose of the Study:
- To review kratom's legal status, chemistry, pharmacology, and toxicology.
- To investigate kratom's potential to cause pharmacokinetic interactions with other drugs.
- To address public health concerns related to kratom use.
Main Methods:
- Review of aggregate in vitro and clinical data.
- Analysis of kratom's effects on cytochrome P450 (P450) enzyme activity.
- Evaluation of P-glycoprotein-mediated efflux activity.
Main Results:
- Kratom and its alkaloids inhibit CYP2D6, CYP3A, and P-glycoprotein.
- These inhibitory effects can increase systemic exposure to co-consumed drugs.
- Polyintoxications and in vitro-in vivo extrapolations suggest significant interaction potential.
Conclusions:
- Kratom can precipitate pharmacokinetic drug interactions.
- Further evaluation using in vitro studies, clinical trials, and pharmacokinetic modeling is warranted.
- Understanding kratom-drug interactions is crucial for public health and safe use.
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