Getryl Mechanism of Action

Oral hypoglycemic agent.
Pharmacology: Mechanism of Action: The primary mechanism of action of glimepiride appears to be dependent on stimulating the release of insulin from functioning pancreatic β-cells.
In addition, extra-pancreatic effects (eg, reduction of basal hepatic glucose production and increased peripheral tissue sensitivity to insulin and glucose uptake) may also play a role in the activity of glimepiride.
However, as with other sulfonylureas, the mechanism by which glimepiride lowers blood glucose during long-term administration has not been clearly established.
Pharmacokinetics: After oral administration, glimepiride is completely absorbed from the GI tract. The oral bioavailability is approximately 100%. Peak plasma concentrations occur in 2-3 hrs. More than 99% of the drug is bound to plasma proteins. Glimepiride is completely metabolized by oxidative biotransformation into 2 main metabolites, a hydroxy derivative and a carboxy derivative.
The elimination t_½ after multiple doses is about 5-8 hrs. Approximately 60% of dose is eliminated in the urine and 40% in the feces.
Specific Populations: Renal Insufficiency: A single-dose clinical study of glimepiride showed that glimepiride serum levels decreased as renal function decreased. However, metabolites serum levels (mean AUC values) increased. The apparent terminal t_½ for glimepiride did not change, while the half-lives for metabolites increased as renal function decreased. Mean urinary excretion of metabolites as percent of dose, however, decreased.