PI-040 - ASSESSING THE GOLDENSEAL-METFORMIN PHARMACOKINETIC INTERACTION IN TYPE 2 DIABETICS.

J. Nguyen¹, C. Arian², M. Cherel¹, D. Hadi^1,3, J. White¹, M. Layton¹, K. Thummel^2,3, N. Cech^4,3, M. Paine^1,3; ¹Washington State University, Spokane, WA, USA, ²University of Washington, Seattle, WA, USA, ³Center of Excellence for Natural Product Drug Interaction Research, Spokane, WA, USA, ⁴University of North Carolina at Greensboro, Greensboro, NC, USA.

Background: The botanical goldenseal precipitated a pharmacokinetic (PK) interaction with metformin in healthy adults (n=16), resulting in a 23% decrease in metformin systemic exposure. This natural product-drug interaction propagated concerns for hyperglycemic complications in type 2 diabetics. A follow-up study was designed to assess the goldenseal-metformin PK interaction and select clinical biomarkers in this patient group.

Methods: Type 2 diabetics (n=20) with HbA1c ≤8% and stabilized on metformin (500-2550 mg daily) participated in a three arm, open-label crossover study. Participants took their pharmacotherapeutic metformin dose without goldenseal (baseline), with a single 3g dose of goldenseal (acute), and while taking 3g goldenseal daily for 28 days (chronic). Plasma and urine were collected (0-24 h) after metformin intake (day 29 of the chronic arm). Metformin PK were evaluated via non-compartmental analysis.

Results: Preliminary metformin PK and clinical biomarker data (n=5 participants) are summarized in the table.

Conclusion: Goldenseal decreased metformin systemic exposure in type 2 diabetic patients. Unexpectedly, the clinical biomarkers HbA1c % and fructosamine decreased, indicating improved glucose control. This natural-product drug interaction is the first to demonstrate a PK interaction offset by an additive clinical effect.

Nguyen, J.T. et al. Assessing Transporter-Mediated Natural Product-Drug Interactions Via In vitro-In Vivo Extrapolation: Clinical Evaluation With a Probe Cocktail. Clin. Pharmacol. Ther.109,1342-1352 (2021).