{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,4]],"date-time":"2026-07-04T03:29:15Z","timestamp":1783135755932,"version":"3.54.6"},"reference-count":40,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2025,2,12]],"date-time":"2025-02-12T00:00:00Z","timestamp":1739318400000},"content-version":"vor","delay-in-days":11,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100006108","name":"National Center for Advancing Translational Sciences","doi-asserted-by":"publisher","award":["TL1 RR025016"],"award-info":[{"award-number":["TL1 RR025016"]}],"id":[{"id":"10.13039\/100006108","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Translational Sci"],"published-print":{"date-parts":[[2025,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Pharmacokinetic drug interactions can lead to unexpected changes in plasma concentrations of the object drug, potentially increasing the risk for adverse effects and\/or decreasing therapeutic efficacy. The botanical product goldenseal was previously shown to decrease metformin systemic exposure in healthy adults. This three\u2010arm, open\u2010label, crossover clinical study assessed the pharmacokinetic goldenseal\u2013metformin interaction in adults with type 2 diabetes stabilized on therapeutic doses of metformin (500\u20132550\u2009mg daily). The aggregate pharmacokinetic data indicated no clinically meaningful interaction as determined by the metformin area under the plasma concentration\u2010time curve (AUC) geometric mean ratio [90% confidence interval] of 0.93 [0.86\u20131.01] laying within the predefined no\u2010effect range (0.80\u20131.25). However, metformin AUC decreased by ~20%, 14%, and 0% after goldenseal coadministration at low (500\u2013750\u2009mg), moderate (1000\u20131500\u2009mg), and high (2000\u20132550\u2009mg) metformin doses, respectively; renal clearance and half\u2010life remained unchanged throughout. The exploratory pharmacodynamic endpoint, HbA1c, decreased on average from 6.8% to 6.5%, regardless of the effects of goldenseal on metformin pharmacokinetics. The decreasing effect of goldenseal on metformin systemic exposure with increasing metformin dose, coupled with no changes in renal excretion and elimination half\u2010life, indicated that both the pharmacokinetic goldenseal\u2013metformin interaction and the nonlinear absorption of metformin are governed by saturable, intestinal transport mechanism(s). The disconnect between changes in metformin systemic exposure and therapeutic effects emphasizes the need to evaluate clinical biomarkers to comprehensively assess drug interaction risks, particularly those involving natural products. Healthcare providers may consider cautioning patients about supplementing metformin pharmacotherapy with goldenseal to avoid risks for undesired changes in glycemic control.<\/jats:p><jats:p><jats:bold>Trial Registration:<\/jats:bold> <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/clinicaltrials.gov\">ClinicalTrials.gov<\/jats:ext-link> identifier: NCT05081583<\/jats:p>","DOI":"10.1111\/cts.70120","type":"journal-article","created":{"date-parts":[[2025,2,13]],"date-time":"2025-02-13T01:40:07Z","timestamp":1739410807000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["The Pharmacokinetic Interaction Between Metformin and the Natural Product Goldenseal Is Metformin Dose\u2010Dependent: A Three\u2010Arm Crossover Study in Adults With Type 2 Diabetes"],"prefix":"10.1111","volume":"18","author":[{"given":"James T.","family":"Nguyen","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Sciences, College of Pharmacy and Pharmaceutical Sciences Washington State University  Spokane Washington USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6595-7717","authenticated-orcid":false,"given":"Christopher M.","family":"Arian","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics, School of Pharmacy University of Washington  Seattle Washington USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rakshit S.","family":"Tanna","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, College of Pharmacy and Pharmaceutical Sciences Washington State University  Spokane Washington USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maxey G.","family":"Cherel","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, College of Pharmacy and Pharmaceutical Sciences Washington State University  Spokane Washington USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3287-9203","authenticated-orcid":false,"given":"Matthew E.","family":"Layton","sequence":"additional","affiliation":[{"name":"Elson S. 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