Evaluation of Systemic and Brain Pharmacokinetic Parameters for Repurposing Metformin Using Intravenous Bolus Administration

Authors

• Sejal Sharma
• Yong Zhang
• Dhavalkumar Patel
• Khondker Ayesha Akter
• Sounak Bagchi
• Ali Ehsan Sifat
• Ehsan Nozohouri
• Yeseul Ahn
• Vardan T Karamyan, Oakland University William Beaumont School of Medicine Faculty
• Ulrich Bickel
• Thomas J Abbruscato

Document Type

Article

Publication Date

1-1-2025

Publication Title

The Journal of pharmacology and experimental therapeutics

Abstract

Metformin's potential in treating ischemic stroke and neurodegenerative conditions is of growing interest. Yet, the absence of established systemic and brain pharmacokinetic (PK) parameters at relevant preclinical doses presents a significant knowledge gap. This study highlights these PK parameters and the importance of using pharmacologically relevant preclinical doses to study pharmacodynamics in stroke and related neurodegenerative diseases. A liquid chromatography with tandem mass spectrometry method to measure metformin levels in plasma, brain, and cerebrospinal fluid was developed and validated. In vitro assays examined brain tissue binding and metabolic stability. Intravenous bolus administration of metformin to C57BL6 mice covered a low- to high-dose range maintaining pharmacological relevance. Quantification of metformin in the brain was used to assess brain PK parameters, such as unidirectional blood-to-brain constant (K

Volume

392

Issue

1

First Page

100013

Last Page

100013

Recommended Citation

Sharma S, Zhang Y, Patel D, et al. Evaluation of systemic and brain pharmacokinetic parameters for repurposing metformin using intravenous bolus administration. J Pharmacol Exp Ther. 2025;392(1):100013. doi:10.1124/jpet.124.002152

DOI

10.1124/jpet.124.002152

ISSN

1521-0103

PubMed ID

39893000