Pharmacology: Pharmacodynamics: Mechanism of Action: Metformin decreases hepatic glucose production, decreases intestinal absorption of glucose and improves insulin sensitivity by increasing peripheral glucose uptake and utilization. Unlike sulfonylureas, metformin does not produce hypogylycemia in either patients with type 2 diabetes or normal subjects (except in special circumstances) and does not cause hyperinsulinemia. With metformin therapy, insulin secretion remains unchanged while fasting insulin levels and day-long plasma insulin response may actually decrease.
Pharmacokinetics: The absolute bioavailability of Metformin tablet given under fasting conditions is approximately 50-60%. Food decreases the extent of and slightly delays the absorption of metformin, as shown by approximately a 40% lower mean peak plasma concentration (Cmax), a 25% lower under the plasma concentration time curve (AUC) and a 35 minute prolongation of time to peak plasma concentration (Tmax) following administration of a single 850mg tablet of metformin with food, compared to the same tablet strength administered fasting. The apparent volume of distribution (V/F) of metformin following single oral doses of Metformin averaged 654+/- 358 L/Metformin is negligibly bound to plasma proteins in contrast to sulfonylureas which are more than 90% protein bound. Metformin partitions into erythrocytes, most likely as a function of time.
Following oral administration, approximately 90% of the absorbed drug is eliminated via the renal route within the first 24 hours, with a plasma elimination half-life is approximately 17.6 hours, suggesting that the erythrocyte mass may be a compartment of distribution.