Indications
Gliclazide is indicated for the management of non-insulin-dependent diabetes mellitus (NIDDM). It is intended to be used as an adjunct to a comprehensive regimen that includes both dietary modifications and physical exercise. This combined approach helps in effectively regulating blood sugar levels in patients with NIDDM.
Pharmacodynamics
As a second-generation sulphonylurea, Gliclazide functions primarily as a hypoglycemic agent. Its primary mechanism of action involves stimulating the beta cells within the islets of Langerhans in the pancreas, leading to increased insulin release. Additionally, Gliclazide enhances the sensitivity of peripheral tissues to insulin, thereby potentiating insulin release and improving overall insulin dynamics.
Absorption
Gliclazide exhibits rapid and efficient absorption following oral administration. However, there is considerable variability in absorption rates both between different individuals and within the same individual over time. Peak plasma concentrations of the drug are typically achieved within four to six hours.
Metabolism
Once absorbed, Gliclazide undergoes extensive hepatic metabolism. Less than 1% of the orally administered dose is excreted unchanged in the urine. The drug is metabolized into various derivatives, including oxidized and hydroxylated forms, along with glucuronic acid conjugates.
Mechanism of Action
Gliclazide operates by attaching to the sulfonylurea receptor (SUR1) located on pancreatic β cells. This interaction inhibits the ATP-sensitive potassium channels, causing these channels to close. As a consequence, potassium efflux is reduced, leading to depolarization of the β cell membrane. This depolarization triggers the opening of voltage-dependent calcium channels, subsequently activating calmodulin. The activation of calmodulin facilitates the exocytosis of insulin-containing secretory granules, thereby stimulating insulin secretion.
