Center of Excellence for Natural Product-Drug Interaction Research

What a journey it's been! The Center of Excellence for Natural Product-Drug Interaction Research (NaPDI Center) is celebrating 10 years of groundbreaking work. Our mission was to bring clarity and consistency to the study of natural product-drug interactions (NPDIs), and we’ve done just that.

Over the past decade, we have:

• Developed a definitive approach to determining the clinical relevance of natural product-drug interactions.

• Created a comprehensive data repository and public website to provide researchers with valuable data and guidance.

• Provided informatics support for selecting high-priority natural products for further study.

• Designed and piloted clinical decision support tools to help healthcare providers and patients avoid adverse NPDIs.

Our research has helped to bridge gaps in evidence and improve public health. Thank you to everyone who has supported our work!

Next up - please visit the new Resource Center for Cannabis and Cannabinoid Research (R3CR) - a collaborative initiative that serves as a central hub for cannabis research resources R3CR and follow the work of the team at the Inland Northwest Human Research Clinic - a service center conducting clinical studies in natural product-drug interaction research - https://labs.wsu.edu/paine/

cc: Washington State University College of Pharmacy and Pharmaceutical Sciences, UNCG Department of Chemistry and Biochemistry, National Institutes of Health (NIH), WSU Murrow College

New insights into green tea and drug interactions

This study highlights the need for improved models to predict drug interactions involving UDP-glucuronosyltransferases (UGTs). The study investigating green tea and raloxifene found an unexpected decrease in raloxifene levels, suggesting that current models may not adequately account for all possible interactions.

Published in Clinical and Translational Science (2023) by Clarke, Judson, Tian, et al

https://pmc.ncbi.nlm.nih.gov/articles/PMC10582660/

tea

Co‐consuming green tea with raloxifene decreases raloxifene systemic exposure in healthy adult participants Green tea is a popular beverage worldwide. The abundant green tea catechin (−)‐epigallocatechin gallate (EGCG) is a potent in vitro inhibitor of intestinal UDP‐glucuronosyltransferase (UGT) activity (K i  ~2 μM). Co‐consuming green tea with ...

Importance of reporting herbal medicine use when taking Paxlovid™ - This study from NaPDI scientists emphasizes the importance of open communication between patients and healthcare providers about herbal medicine use when taking Paxlovid™. It highlights the lack of comprehensive data on HDIs involving Paxlovid™ and stresses the need for further research and awareness to prevent adverse events and ensure optimal treatment outcomes.

Published in Frontiers in Pharmacology by Smith, Bi, Hamman, Ma, et al

https://pmc.ncbi.nlm.nih.gov/articles/PMC10368978/

Potential pharmacokinetic interactions with concurrent use of herbal medicines and a ritonavir-boosted COVID-19 protease inhibitor in low and middle-income countries The COVID-19 pandemic sparked the development of novel anti-viral drugs that have shown to be effective in reducing both fatality and hospitalization rates in patients with elevated risk for COVID-19 related morbidity or mortality. Currently, ...

Goldenseal & Metformin: What you need to know about this drug interaction

This study in mice suggests that goldenseal, a common herbal supplement, may decrease metformin's effectiveness by inhibiting intestinal uptake transporters. While further research is needed, this finding highlights the importance of discussing potential interactions with your healthcare provider before taking any herbal supplements, especially when combined with medications.

Published in Drug Metabolism and Disposition by Oyanna, Garcia-Torres, Bechtold et al

https://pmc.ncbi.nlm.nih.gov/articles/PMC10586506/

Goldenseal-Mediated Inhibition of Intestinal Uptake Transporters Decreases Metformin Systemic Exposure in Mice Goldenseal is a perennial plant native to eastern North America. A recent clinical study reported goldenseal decreased metformin Cmax and area under the blood concentration versus time curve (AUC) by 27% and 23%, respectively, but half-life and ...

Green tea catechins impact raloxifene solubility. A study in mice found that green tea extract reduced raloxifene's peak concentration in the blood. Further investigation showed that EGCG and EGC, major catechins in green tea, decreased raloxifene's solubility in a fasted state simulated intestinal fluid.

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Published in Pharmaceutical Research (2024) by Oyanna, Bechtold, Lynch, Ridge Call, Graf, Oberlies, Clarke.

https://link.springer.com/article/10.1007/s11095-024-03662-w

This research was supported by grant U54 AT0008909 from the National Institutes of Health National Center for Complementary and Integrative Health

Green Tea Catechins Decrease Solubility of Raloxifene In Vitro and Its Systemic Exposure in Mice - Pharmaceutical Research Purpose Green tea is a widely consumed beverage. A recent clinical study reported green tea decreased systemic exposure of raloxifene and its glucuronide metabolites by 34–43%. However, the underlying mechanism(s) remains unknown. This study investigated a change in raloxifene’s solubility as th...

What are your thoughts on kratom? It's important to be informed about its potential effects. A recent study highlights that kratom can interact with certain medications, potentially affecting their effectiveness and safety.
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Published in Clinical Pharmacology & Therapeutics (2023) by Tanna, Nguyen, Hadi et al

View full article at https://ascpt.onlinelibrary.wiley.com/doi/10.1002/cpt.2891

This work was supported by the National Institutes of Health National Center for Complementary and Integrative Health and the Office of Dietary Supplements via the Center of Excellence for Natural Product Drug Interaction Research (U54 AT008909), including an administrative supplement (U54 AT008909-04S2).

Clinical Assessment of the Drug Interaction Potential of the Psychotropic Natural Product Kratom Oral formulations prepared from the leaves of the kratom (Mitragyna speciosa) plant are increasingly used for their opioid-like effects to self-manage opioid withdrawal and pain. Calls to US poison c...

The potential for drugs to disrupt nutrient absorption through intestinal transporters calls for further research. The review highlights the importance of investigating the time dependence of transporter inhibition, identifying potential compensatory mechanisms, and exploring the role of intestinal transporters in disease development. Understanding these interactions is crucial for improving patient care.

View full article: https://www.mdpi.com/1999-4923/16/4/447
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Published in Pharmaceutics by Kharve, Engley, Paine, Sprowl (2024)

This work was supported in part by the National Institutes of Health, National Institute of General Medical Sciences, under Award Number 1R01GM139936 (to J.A.S.); the National Institute on Deafness and Other Communication Disorders under Award Number 1R21DC021031 (to J.A.S.); and the National Center for Complementary and Integrative Health under Award Number U54AT008909 (to M.F.P.).

Impact of Drug-Mediated Inhibition of Intestinal Transporters on Nutrient and Endogenous Substrate Disposition…an Afterthought? A large percentage (~60%) of prescription drugs and new molecular entities are designed for oral delivery, which requires passage through a semi-impervious membrane bilayer in the gastrointestinal wall. Passage through this bilayer can be dependent on membrane transporters that regulate the absorpti...

This study examines the absorption, distribution, metabolism, and excretion of kratom alkaloids in humans. This research is crucial for understanding the potential risks and benefits of this popular botanical product.

Published in Pharmaceutics by Tanna, Nguyen, Hadi, Manwill et al

https://www.mdpi.com/1999-4923/14/3/620

Clinical Pharmacokinetic Assessment of Kratom (Mitragyna speciosa), a Botanical Product with Opioid-like Effects, in Healthy Adult Participants Increasing use of the botanical kratom to self-manage opioid withdrawal and pain has led to increased kratom-linked overdose deaths. Despite these serious safety concerns, rigorous fundamental pharmacokinetic knowledge of kratom in humans remains lacking. We assessed the pharmacokinetics of a single...

A recent study published in Journal of American Medical Association Network (JAMA) sheds light on how CBD interacts with THC in the body. Researchers found that high doses of oral CBD can significantly impact THC metabolism, leading to prolonged and potentially stronger effects. This highlights the importance of understanding the potential interactions between CBD and THC, particularly for individuals using cannabis products for therapeutic or recreational purposes.
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Published in the Journal of American Medical Association Network (JAMA) (2023) by Zamarripa, Spindle, et al

https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2801352

This research was supported by grant U54 AT0008909 from the National Institutes of Health National Center for Complementary and Integrative Health and grants T32 DA007209 and P01 DA032507 from the National Institute on Drug Abuse.

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Assessment of Orally Administered Δ9-THC When Coadministered With CBD This randomized clinical trial compares the pharmacokinetics and pharmacodynamics of orally administered Δ9-tetrahydrocannabinol (THC)-dominant and cannabidiol-dominant cannabis extracts that contained the same Δ9-THC dose in a healthy adult population of US adults.

Fexofenadine: Insights into limited sampling for transporter activity assessment

This study examines limited sampling strategies for fexofenadine in healthy adults and highlights the importance of thorough validation. The research found that commonly used fexofenadine limited sampling models failed to accurately estimate exposure, suggesting limitations in their use for assessing P-gp and OATP1B1/3 activities. Further research is needed to develop robust limited sampling approaches for transporter phenotyping.

Published in International Journal of Clinical Pharmacology and Therapeutics (2023) Liyanage, Blaquera, Piscitelli et al

https://pmc.ncbi.nlm.nih.gov/articles/PMC10339714/

Limitations of fexofenadine limited sampling strategy using plasma concentrations and partial area under the concentration-time curve to estimate transporter activity in healthy adults Objective: Fexofenadine is a probe drug used to phenotype P-glycoprotein (P-gp) and organic anion transporting polypeptide (OATP) 1B1/3 activities. This study evaluated a limited sampling strategy using plasma concentrations and/or partial area ...

Understand the impact of green tea on drug absorption. Researchers have discovered that green tea extract and EGCG (a key catechin) can decrease the solubility of raloxifene in simulated intestinal fluids. This finding may explain why green tea consumption can reduce the systemic exposure of this medication.
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Published in Pharmaceutical Research (2024) by Oyanna, Bechtold, Lynch, Ridge Call, Graf, Oberlies, Clarke.

https://link.springer.com/article/10.1007/s11095-024-03662-w

This research was supported by grant U54 AT0008909 from the National Institutes of Health National Center for Complementary and Integrative Health

Green Tea Catechins Decrease Solubility of Raloxifene In Vitro and Its Systemic Exposure in Mice - Pharmaceutical Research Purpose Green tea is a widely consumed beverage. A recent clinical study reported green tea decreased systemic exposure of raloxifene and its glucuronide metabolites by 34–43%. However, the underlying mechanism(s) remains unknown. This study investigated a change in raloxifene’s solubility as th...

Grapefruit juice impacts Fexofenadine pharmacokinetics

This study found that grapefruit juice significantly decreased the relative oral bioavailability of fexofenadine. This suggests that grapefruit juice may interact with P-gp and OATP1B1/3, the transporters fexofenadine is used to study. This finding emphasizes the importance of considering the impact of food and beverages on drug interactions.

Published in Therapeutic Drug Monitoring (2024) by Piscitelli, Nikanjam, Capparelli et al

https://pmc.ncbi.nlm.nih.gov/articles/PMC10123170/

Fexofenadine Plasma Concentrations to Estimate Systemic Exposure in Healthy Adults Using a Limited Sampling Strategy with a Population Pharmacokinetic Approach Fexofenadine is a recommended in vivo probe drug for phenotypic P-glycoprotein (P-gp) and organic anion transporting polypeptide (OATP) 1B1/3 transporter activities. This study evaluated a limited sampling strategy using a population pharmacokinetic ...