Diamicron/Diamicron MR 60 Mechanism of Action

Pharmacology: Pharmacodynamics: Gliclazide reduces blood glucose by stimulating insulin secretion from the β-cells in the islets of Langerhans.
Pharmacodynamic effects: Effects on insulin release: In type 2 diabetics, gliclazide restores the first peak of insulin secretion in response to glucose and increases the second phase of insulin secretion.
A significant increase in insulin response is seen in response to stimulation induced by a meal or glucose.
Hemo-vascular properties: Gliclazide decreases microthrombosis by two mechanisms which may be involved in complications of diabetes: a partial inhibition of platelet aggregation and adhesion, with a decrease in the markers of platelet activation (beta thromboglobulin, thromboxane B2).
An action on the vascular endothelium fibrinolytic activity with an increase in tPA activity.
Diamicron MR 60: Mechanism of action: Gliclazide is a hypoglycemic sulfonylurea oral antidiabetic active substance differing from other related compounds by an N-containing heterocyclic ring with an endocyclic bond.
Increase in postprandial insulin and C-peptide secretion persists after two years of treatment.
In addition to these metabolic properties, gliclazide has hemovascular properties.
Pharmacokinetics: Diamicron: Gliclazide is rapidly absorbed from the gastrointestinal tract, and the concentration in the blood reaches a maximum 11-14 hours after administration.
In humans, binding to proteins is 94.2%.
As the apparent terminal elimination half-life for gliclazide is 20 hours in humans, the drug can be administered in two daily doses.
Elimination is mainly in the urine: less than 1% of the dose ingested is found unchanged in the urine.
Diamicron MR 60: Absorption: Plasma levels increase progressively during the first 6 hours, reaching a plateau which is maintained from the sixth to the twelfth hour after administration.
Intra-individual variability is low.
Gliclazide is completely absorbed. Food intake does not affect the rate or degree of absorption.
Distribution: Plasma protein binding is approximately 95%. The volume of distribution is around 30 liters.
A single daily intake of GLICLAZIDE (DIAMICRON MR) 60 mg maintains effective gliclazide plasma concentrations over 24 hours.
Biotransformation: Gliclazide is mainly metabolized in the liver and excreted in the urine: less than 1% of the unchanged form is found in the urine. No active metabolites have been detected in plasma.
Elimination: The elimination half-life of gliclazide varies between 12 and 20 hours.
Linearity/non-linearity: The relationship between the dose administered ranging up to 120 mg and the area under the concentration time curve is linear.
Special populations: Elderly: No clinically significant changes in pharmacokinetic parameters have been observed in elderly patients.