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

Clinical Pharmacology and Therapeutics
Maciej J Zamek-GliszczynskiInternational Transporter Consortium

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.

References

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Jun 23, 2012·Pharmacogenetics and Genomics·Li GongTeri E Klein
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Jul 26, 2014·British Journal of Clinical Pharmacology·Sung Kweon ChoJae-Yong Chung
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Apr 6, 2017·Clinical Pharmacology and Therapeutics·Eio SundelinN Jessen

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Citations

Aug 24, 2018·Clinical Pharmacology and Therapeutics·Kathleen M GiacominiShiew Mei Huang
Oct 3, 2018·Clinical Pharmacology and Therapeutics·Lei ZhangIssam Zineh
Mar 28, 2019·Clinical Pharmacology and Therapeutics·Aleksi TornioJanne T Backman
Mar 2, 2021·International Journal of Endocrinology·Xiaowen HuShuguang Pang
Sep 4, 2021·Cancer Chemotherapy and Pharmacology·Ken OgasawaraGopal Krishna
Aug 5, 2021·Drug Metabolism Reviews·Paresh P ChotheKimio Tohyama

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