ACCUMULATION OF METFORMIN BY TISSUES OF THE NORMAL AND DIABETIC MOUSE

1. Tissue accumulation of the antihyperglycaemic agent metformin (dime thylbiguanide) was examined after oral administration to the normal an d streptozotocin (STZ) diabetic mouse. 2. Metformin (50 mg/kg body wei ght containing C-14-metformin 2 mu Ci/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 concentra tions (mu mol/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 mu mol/kg wet weight at 0.5-2 h, but decli ned to < 2% of maximum by 24 h. 4. Stomach, colon, salivary gland, kid ney and liver accumulated metformin more than two-fold, and concentrat ions of the drug in heart and skeletal (gastrocnemius) muscle were gre ater than plasma concentrations on some occasions up to 8 h. 5. In a s eparate study, i.v.-administered metformin was selectively accumulated by tissues of the small intestine. Thus, retention of metformin by ti ssues of the small intestine may represent a deep compartment for the drug.