The Pharmacokinetic Interaction Between Metformin and the Natural Product Goldenseal Is Metformin Dose-Dependent: A Three-Arm Crossover Study in Adults With Type 2 Diabetes
Abstract
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-arm, open-label, crossover clinical study assessed the pharmacokinetic goldenseal-metformin interaction in adults with type 2 diabetes stabilized on therapeutic doses of metformin (500-2550 mg daily). The aggregate pharmacokinetic data indicated no clinically meaningful interaction as determined by the metformin area under the plasma concentration-time curve (AUC) geometric mean ratio [90% confidence interval] of 0.93 [0.86-1.01] laying within the predefined no-effect range (0.80-1.25). However, metformin AUC decreased by ~20%, 14%, and 0% after goldenseal coadministration at low (500-750 mg), moderate (1000-1500 mg), and high (2000-2550 mg) metformin doses, respectively; renal clearance and half-life 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-life, indicated that both the pharmacokinetic goldenseal-metformin interaction and the nonlinear absorption…
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Evidence Hub reads this as a randomized trial, done in people. Its evidence level is 2 of 5 (High · randomized trial). Randomized trials of a reasonable size are the strongest single-study design.
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