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ITC Commentary on Metformin Clinical Drug–Drug Interaction Study Design That Enables an Efficacy‐ and Safety‐Based Dose Adjustment Decision

Year: 2018
Type: article
Abstract: Metformin drug-drug interaction (DDI) studies are conducted during development of drugs that inhibit organic cation transporters and/or multidrug and toxin extrusion proteins (OCTs/MATEs). Monitoring solely changes in systemic exposure, the typical DDI study endpoint appears inadequate for metformin, which is metabolically stable, has poor passive membrane permeability, and undergoes transporter-mediated tissue distribution and clearance. Evaluation of renal clearance, antihyperglycemic effects, and potentially lactate as an exploratory safety marker, can support rational metformin dose adjustment. The proposed DDI study design aims to adequately inform metformin dosing during comedication.
DOI: 10.1002/cpt.1082
Authors: Maciej J. Zamek‐Gliszczynski, Xiaoyan Chu, Jack A. Cook, Joseph M. Custodio, Aleksandra Galetin, Kathleen M. Giacomini, Caroline A. Lee, Mary F. Paine, Adrian S. Ray, Joseph A. Ware, Matthias B. Wittwer, Lei Zhang
Institutions: GlaxoSmithKline (United States), Merck & Co., Inc., Rahway, NJ, USA (United States), Pfizer (United States), Gilead Sciences (United States), University of Manchester, University of California, San Francisco, Washington State University Spokane, Genentech, Roche (Switzerland), United States Food and Drug Administration, Center for Drug Evaluation and Research
Language: English
Subfield: Pharmacology
Open Access status: green
OpenAlex ID: W2804156033
FWCI: 3.674
Cites: 10
Cited by: 37
Related to: 10