Pharmacotherapeutic Group: Sulfonamides, urea derivatives. ATC Code: A10BB09.
Pharmacology: Pharmacodynamics: Gliclazide is a hypoglycaemic sulfonylurea 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 2 years of treatment.
In addition to these metabolic properties, gliclazide has haemovascular properties.
Effects on Insulin Release: In type 2 diabetics, gliclazide restores the 1st peak of insulin secretion in response to glucose and increases the 2nd 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 2 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 (β-thromboglobulin, thromboxane B2); an action on the vascular endothelium fibrinolytic activity with an increase in tPA activity.
Pharmacokinetics: Plasma levels increase progressively during the first 6 hrs, reaching a plateau which is maintained from the 6th-12th hr after administration.
Intraindividual variability is low.
Gliclazide is completely absorbed. Food intake does not affect the rate or degree of absorption. The relationship between the dose administered ranging up to 120 mg and the area under the concentration time curve is linear.
Plasma protein binding is approximately 95%.
Gliclazide is mainly metabolised in the liver and excreted in the urine: <1% of the unchanged form is found in the urine. No active metabolites have been detected in plasma.
The elimination half-life of gliclazide varies between 12 and 20 hrs.
The volume of distribution is around 30 L.
No clinically significant changes in pharmacokinetic parameters have been observed in elderly patients.
A single daily intake of Diamicron MR 60 mg maintains effective gliclazide plasma concentrations over 24 hrs.
Toxicology: Preclinical Safety Data: Preclinical data reveal no special hazards for humans based on conventional studies of repeated dose toxicity and genotoxicity. Long-term carcinogenicity studies have not been done.
Teratogenicity: No teratogenic changes have been shown in animal studies, but lower foetal body weight was observed in animals receiving doses 25-fold higher than the maximum recommended dose in humans.