PHARMACOKINETICS OF METFORMIN AFTER INTRAVENOUS AND ORAL-ADMINISTRATION TO MAN

The kinetics of the antidiabetic 14C-metformin were studied in 5 healthy subjects after oral and i.v. administration. The i.v. dose was distributed to a small central compartment of 9.9 .+-. 1.61 (.hivin.X .+-. SE), from which its elimination could be described using 3-compartment open model. The elimination half-life from plasma was 1.7 .+-. 0.1 h. Urinary excretion data revealed a quantitatively minor terminal elimination phase with a half-life of 8.9 .+-. 0.7 h. After the i.v. dose, metformin was completely excreted unchanged in urine with a renal clearance of 454 .+-. 47 ml/min. Metformin was not bound to plasma proteins. The concentration of metformin in saliva was considerably lower than in plasma and declined more slowly. The bioavailability of metformin tablets averaged 50-60%. The rate of absorption was slower than that of elimination, which caused a plasma concentration profile of flip-flop type for oral metformin.