Twenty-four hours after oral administration of metformin-14C to mice (100 mg/kg), an average of 77.2% of the administered activity was recovered in the urine and 8.4% in the faeces. Under the same test conditions the rat eliminated 66.8% of the administered dose in the urine and 18.4% with the faeces. Less than 1% of the radioactivity was found in the bile. Unchanged metformin was the only radioactive substance which appeared in the urine of rats and mice. The investigation comparing the distributions of buformin-14C and of metformin-14C in the body organs gave a similar picture for both biguanides. The highest biguanide concentrations were found in the kidneys, adrenals, pancreas and liver. Serum concentrations amounted to an average of 1.2 μg/ml after oral administration of 50 mg buformin-14C/kg and 6.2 μg/ml after 150 mg metformin-14C/kg. Healthy human volunteers eliminated an average of 63% of the administered dose in the urine within 36 h. Metformin was not metabolized by the human being. From the rate of elimination in the urine, the biological half-life of the biguanide was found to be 2.8 h. Compared with other biguanides the weak hypoglycaemic activity of metformin in both animals and diabetics cannot be explained by low absorption. It is due to the weak intrinsic activity of this biguanide as such. © 1969 Springer-Verlag.
