Determination of metformin bio-distribution by LC-MS/MS in mice treated with a clinically relevant paradigm.

PloS One
Kiran ChaudhariShao-Hua Yang

Abstract

Metformin, an anti-diabetes drug, has been recently emerging as a potential "anti-aging" intervention based on its reported beneficial actions against aging in preclinical studies. Nonetheless, very few metformin studies using mice have determined metformin concentrations and many effects of metformin have been observed in preclinical studies using doses/concentrations that were not relevant to therapeutic levels in human. We developed a liquid chromatography-tandem mass spectrometry protocol for metformin measurement in plasma, liver, brain, kidney, and muscle of mice. Young adult male and female C57BL/6 mice were voluntarily treated with metformin of 4 mg/ml in drinking water which translated to the maximum dose of 2.5 g/day in humans. A clinically relevant steady-state plasma metformin concentrations were achieved at 7 and 30 days after treatment in male and female mice. Metformin concentrations were slightly higher in muscle than in plasma, while, ~3 and 6-fold higher in the liver and kidney than in plasma, respectively. Low metformin concentration was found in the brain at ~20% of the plasma level. Furthermore, gender difference in steady-state metformin bio-distribution was observed. Our study established steady-state met...Continue Reading

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Citations

Jul 3, 2021·Pharmaceuticals·Yoo-Seong Jeong, William J Jusko
May 8, 2021·Diabetes·Linh NguyenAdrian Kee Keong Teo
Oct 22, 2021·Biochemical Pharmacology·Walter H MoosKonstantina Sampani

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Methods Mentioned

BETA
blood collection
NMR
transgenic

Clinical Trials Mentioned

NCT02432287

Software Mentioned

Agilent Mass Hunter
Mass Hunter Quantitative analysis

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