Pharmacology: Pharmacodynamics: Gliclazide is a hypoglycaemic sulphonylurea oral antidiabetic active substance differing from other related compounds by an N-containing heterocyclic ring with an endocyclic bond.
Gliclazide reduces blood glucose levels by stimulating insulin secretion from the β-cells of the islets of Langerhans. Increase in postprandial insulin and C-peptide secretion persists after two years of treatment. In addition to these metabolic properties, gliclazide has haemovascular properties.
Effects in insulin release response to stimulation induced by a meal or glucose: 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.
Haemovascular 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.
Pharmacokinetics: Absorption: Plasma levels increase progressively during the first 6 hours, reaching a plateau which is maintained from the 6 to 12 hours 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 litres. A single daily intake of Plecaz MR 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.
Elderly: No clinically significant changes in pharmacokinetic parameters have been observed in elderly patients.