Pharmacotherapeutic group: SULFONYLUREA - ORAL ANTIDIABETIC (A: Alimentary tract and metabolism). ATC code: A10BB09.
Pharmacology: Pharmacodynamics: Mechanism of action: Gliclazide reduces blood glucose levels by stimulating the insulin secretion βcells 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.
Haemovascular properties: Gliclazide decreases microthrombosis by two mechanisms which may be involved in the 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: Gliclazide is rapidly absorbed from the gastrointestinal tract and maximum blood concentrations are attained between the 11th and the 14th hour after administration.
Distribution: In humans, binding to proteins is 94.2%.
Elimination: 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.
Toxicology: Preclinical safety data: Non-clinical data reveal no special hazard for humans based on conventional studies of repeated dose toxicity and genotoxicity. Long term carcinogenicity studies have not been done.
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.
Fertility and reproductive performance were unaffected after gliclazide administration in animal studies.