Gliclazide (S1702) further explains the mechanism underlying its hypoglycemic effect: the drug's insulinotropic sulfonylurea effect is further enhanced by the observed improvements in GLUT4 translocation and insulin sensitivity, which counteract the insulin resistance that hydrogen peroxide causes in 3T3L1 adipocytes [1]. Gliclazide demonstrated a significant reduction in efficacy in cardiac and smooth muscle, with IC50s of 19.5 +/- 5.4 micromol/l (n = 6–12) and 37.9 +/– 1.0 micromol/l (n = 5–10), respectively. However, it was significantly more effective in blocking whole-cell beta-cell KATP currents in this latter tissue. The drug affected whole-cell KATP currents in all three tissues, but its effects were quickly reversible. Gliclazide (1 micromol/l) on beta-cells led to a maximum of 66 +/- 13% inhibition (n=5) in inside-out patches, while over 98% block was produced in the whole-cell configuration. is a high-potency sulphonylurea that exhibits over heart and smooth muscle specificity for the pancreatic beta-cell KATP channel. It stands apart from glibenclamide in this regard[2].

N/A

Absorption, Distribution and Excretion
Rapidly and well absorbed but may have wide inter- and intra-individual variability. Peak plasma concentrations occur within 4-6 hours of oral administration.
Metabolites and conjugates are eliminated primarily by the kidneys (60-70%) and also in the feces (10-20%).

---

Metabolism / Metabolites
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.
Gliclazide has known human metabolites that include Methylhydroxygliclazide, 6-hydroxy-gliclazide, and 7-hydroxy-gliclazide.

---

Biological Half-Life
10.4 hours. Duration of action is 10-24 hours.

Protein Binding
94%, highly bound to plasma proteins

[1]. Gliclazide protects 3T3L1 adipocytes against insulin resistance induced by hydrogen peroxide with restoration of GLUT4 translocation. Metabolism, 2006. 55(6): p. 722-30.

[2]. Gliclazide produces high-affinity block of KATP channels in mouse isolated pancreatic beta cells but not rat heart or arterial smooth muscle cells. Diabetologia, 2001. 44(8): p. 1019-25.

Gliclazide is a N-sulfonylurea. It has a role as a hypoglycemic agent, a radical scavenger and an insulin secretagogue.
Gliclazide is an oral antihyperglycemic agent used for the treatment of non-insulin-dependent diabetes mellitus (NIDDM). It has been classified differently according to its drug properties in which based on its chemical structure, gliclazide is considered a first-generation sulfonylurea due to the structural presence of a sulfonamide group able to release a proton and the presence of one aromatic group. On the other hand, based on the pharmacological efficacy, gliclazide is considered a second-generation sulfonylurea which presents a higher potency and a shorter half-life. Gliclazide belongs to the sulfonylurea class of insulin secretagogues, which act by stimulating β cells of the pancreas to release insulin. Sulfonylureas increase both basal insulin secretion and meal-stimulated insulin release. Medications in this class differ in their dose, rate of absorption, duration of action, route of elimination and binding site on their target pancreatic β cell receptor. Sulfonylureas also increase peripheral glucose utilization, decrease hepatic gluconeogenesis and may increase the number and sensitivity of insulin receptors. Sulfonylureas are associated with weight gain, though less so than insulin. Due to their mechanism of action, sulfonylureas may cause hypoglycemia and require consistent food intake to decrease this risk. The risk of hypoglycemia is increased in elderly, debilitated and malnourished individuals. Gliclazide has been shown to decrease fasting plasma glucose, postprandial blood glucose and glycosolated hemoglobin (HbA1c) levels (reflective of the last 8-10 weeks of glucose control). Gliclazide is extensively metabolized by the liver; its metabolites are excreted in both urine (60-70%) and feces (10-20%).
Gliclazide is a short-acting, relatively high-potency, second-generation sulfonylurea compound with hypoglycemic activity. Gliclazide also increases peripheral insulin sensitivity. This agent is metabolized by CYP2C9.
An oral sulfonylurea hypoglycemic agent which stimulates insulin secretion.

---

Drug Indication
For the treatment of NIDDM in conjunction with diet and exercise.

---

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.

---

Pharmacodynamics
Based on the pharmacological properties, 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.

C15H21N3O3S

323.41

323.13

21187-98-4

Gliclazide-d4;1185039-30-8

3475

White to off-white solid powder

1.4±0.1 g/cm3

163-169 °C(lit.)

1.624

1.57

2

4

3

22

497

0

BOVGTQGAOIONJV-UHFFFAOYSA-N

InChI=1S/C15H21N3O3S/c1-11-5-7-14(8-6-11)22(20,21)17-15(19)16-18-9-12-3-2-4-13(12)10-18/h5-8,12-13H,2-4,9-10H2,1H3,(H2,16,17,19)

1-(3,3a,4,5,6,6a-hexahydro-1H-cyclopenta[c]pyrrol-2-yl)-3-(4-methylphenyl)sulfonylurea

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Solubility in Formulation 1: ≥ 2.5 mg/mL (7.73 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

---

Solubility in Formulation 2: ≥ 2.5 mg/mL (7.73 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

---

View More

Solubility in Formulation 3: ≥ 2.5 mg/mL (7.73 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

---

 (Please use freshly prepared in vivo formulations for optimal results.)