| Indication | For the treatment of NIDDM in conjunction with diet and exercise. |
| Pharmacodynamics | Gliclazide is a second generation sulphonylurea which acts as a hypoglycemic agent. It stimulates β cells of the islet of Langerhans in the pancreas to release insulin. It also enhances peripheral insulin sensitivity. Overall, it potentiates insulin release and improves insulin dynamics. |
| Mechanism of action | Gliclazide binds to the β cell sulfonyl urea receptor (SUR1). This binding subsequently blocks the ATP sensitive potassium channels. The binding results in closure of the channels and leads to a resulting decrease in potassium efflux leads to depolarization of the β cells. This opens voltage-dependent calcium channels in the β cell resulting in calmodulin activation, which in turn leads to exocytosis of insulin containing secretorty granules. |
| Absorption | Rapidly and well absorbed but may have wide inter- and intra-individual variability. Peak plasma concentrations occur within 4-6 hours of oral administration. |
| Volume of distribution | Not Available |
| Protein binding | 94%, highly bound to plasma proteins |
| Metabolism | Extensively metabolized in the liver. Less than 1% of the orally administered dose appears unchanged in the urine. Metabolites include oxidized and hydroxylated derivates, as well as glucuronic acid conjugates. |
| Route of elimination | Metabolites and conjugates are eliminated primarily by the kidneys (60-70%) and also in the feces (10-20%). |
| Half life | 10.4 hours. Duration of action is 10-24 hours. |
| Clearance | Not Available |
| Toxicity | LD50=3000 mg/kg (orally in mice). Gliclazide and its metabolites may accumulate in those with severe hepatic and/or renal dysfunction. Symptoms of hypoglycemia include: dizziness, lack of energy, drowsiness, headache and sweating. |