Accumulation of metformin by tissues of the normal and diabetic mouse

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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 25μCi/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 (μmol/1, 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 μmol/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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