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

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

doi:10.1002/cpt.1082

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

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

^*Corresponding author for this work

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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.

Original language	English
Journal	Clinical Pharmacology and Therapeutics
Early online date	15 May 2018
DOIs	https://doi.org/10.1002/cpt.1082
Publication status	Published - 2018

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Zamek-Gliszczynski, M. J., Chu, X., Cook, J. A., Custodio, J. M., Galetin, A., Giacomini, K. M., Lee, C. A., Paine, M. F., Ray, A. S., Ware, J. A., Wittwer, M. B., & Zhang, L. (2018). ITC Commentary on Metformin Clinical Drug-Drug Interaction Study Design That Enables an Efficacy- and Safety-Based Dose Adjustment Decision. Clinical Pharmacology and Therapeutics. https://doi.org/10.1002/cpt.1082

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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.",

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AU - Zamek-Gliszczynski, Maciej J.

AU - Chu, Xiaoyan

AU - Cook, Jack A.

AU - Custodio, Joseph M.

AU - Galetin, Aleksandra

AU - Giacomini, Kathleen M.

AU - Lee, Caroline A.

AU - Paine, Mary F.

AU - Ray, Adrian S.

AU - Ware, Joseph A.

AU - Wittwer, Matthias B.

AU - Zhang, Lei

PY - 2018

Y1 - 2018

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AB - 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.

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U2 - 10.1002/cpt.1082

DO - 10.1002/cpt.1082

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AN - SCOPUS:85047634179

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JO - Clinical Pharmacology and Therapeutics

JF - Clinical Pharmacology and Therapeutics

ER -

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

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