Accumulation of Metformin by Tissues of the Normal and Diabetic Mouse
Abstract
1. Tissue accumulation of the antihyperglycaemic agent metformin (dimethylbiguanide) was examined after oral administration to the normal and streptozotocin (STZ) diabetic mouse. 2. Metformin (50 mg/kg body weight containing 14C-metformin 25 microCi/kg body weight), which is stable and not metabolized, resulted in maximum plasma concentrations at 0.5 h which declined to < 5% of maximum by 24 h. Maximum plasma concentrations (mumol/l, mean +/- SE) in the hepatic portal vein (normal 51.7 +/- 5.4, STZ 61.5 +/- 8.0) were higher than in the inferior vena cava (normal 29.0 +/- 2.8, STZ 35.4 +/- 5.9). 3. The greatest accumulation of metformin occurred in tissues of the small intestine, where maximum concentrations were > 1000 mumol/kg wet weight at 0.5-2 h, but declined to < 2% of maximum by 24 h. 4. Stomach, colon, salivary gland, kidney and liver accumulated metformin more than two-fold, and concentrations of the drug in heart and skeletal (gastrocnemius) muscle were greater than plasma concentrations on some occasions up to 8 h. 5. In a separate study, i.v.-administered metformin was selectively accumulated by tissues of the small intestine. Thus, retention of metformin by tissues of the small intestine may represent a deep compartment for the drug.
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In both Arunachalam et al. and Ghosh et al., 50 μM metformin was used and justified on the basis that estimates of metformin levels in portal circulation following oral absorption are between 40 and 70 μM.
“In both studies, Arunachalam et al. (110) and Ghosh et al. (111) used 50 μM metformin and justified this concentration on the basis that estimates of metformin levels in the portal circulation following oral absorption are between 40 and 70 μM (4, 181).”
From A Critical Review of the Evidence That Metformin Is a Putative Anti-Aging Drug That Enhances Healthspan and Extends Lifespan (2021) · cites this paper as [181]
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- Authors
- Wilcock, C., & Bailey, C. J.
- Affiliations
- Aston University (GB)
- ORCID
- Bailey, C. J.
- Venue
- Xenobiotica
- Publisher
- Informa UK Limited
- Published
- 1994-01
- Volume
- 24
- Issue
- 1
- Pages
- 49-57
- ISSN
- 0049-8254 (ISSN-L)
- 1366-5928
- OpenAlex
- W2136667764
- Cited by
- 418
- References
- 23
- Citations by year
- 2026: 6 · 2025: 14 · 2024: 20 · 2023: 23 · 2022: 22 · 2021: 23 · 2020: 21 · 2019: 24 · 2018: 30 · 2017: 31 · 2016: 26 · 2015: 31 · 2014: 30 · 2013: 19 · 2012: 12
- FWCI
- 2.92
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Xenobiotica (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Pharmacogenetics and Drug Metabolism
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Keywords
- metformin, tissue accumulation, streptozotocin-induced diabetes, small intestine, drug retention, plasma concentration, oral administration, antidiabetic drugs, drug distribution
- MeSH terms
- Administration, Oral, Animals, Diabetes Mellitus, Experimental, Digestive System, Injections, Intravenous, Male, Metformin, Mice, Inbred Strains, Tissue Distribution, Mice
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