Source: Health Products Regulatory Authority (IE) Revision Year: 2020 Publisher: L. Molteni & C. dei F.lli Alitti, Strada Statale 67, Localita Granatieri, Scandicci, Firenze, Italy
Pharmaco-therapeutic group: oral blood glucose lowering drugs sulphonylureas; gliclazide
ATC code: A10BB09
Gliclazide, like other sulphonylureas, reduces blood glucose levels in healthy volunteers and in patients with non-insulin-dependent diabetes mellitus by correcting both defective insulin secretion and peripheral insulin resistance.
Unstimulated and stimulated insulin secretion from pancreatic beta-cells is increased following administration of gliclazide, with both the first and second phases of secretion being affected.
The extra pancreatic effects restore peripheral insulin sensitivity, such as decreasing hepatic glucose production, and increasing glucose clearance and skeletal muscle glycogen synthase activity. These effects do not appear to be mediated by an effect on insulin receptor numbers, affinity and function.
Gliclazide has specific haemobiological effects in that it causes a reduction in platelet adhesiveness and aggregation, it increases the release of plasminogen activator by the vascular walls, and, by increasing the superoxide dismutase activity, reduces free radical levels.
Clinical data suggest that long-term administration of gliclazide may delay the progression of diabetic retinopathy to a greater extent than other sulphonylureas or diet.
Gliclazide is extensively absorbed by the gastrointestinal tract, but absorption rate varies considerably, and individuals can be classified as slow or fast absorbers.
Our bioequivalence trial carried out with a 80-mg dose on 20 male healthy volunteers aged 33 ± 7 years, showed a Cmax of 2.652 ± 0.651 mg/L (test) and 2.647 ± 0.542 mg/L (reference) and tmax was 9 h (3-9) and 7.5 h (3-12), respectively. Steady-state concentrations are reached after 2 days' administration.
The mean plasma half life is 10 h and the volume of distribution is about 25L. Renal insufficiency associated to diabetes prolongs the plasma half-life slightly, but not significantly; therefore, dosage alterations are not normally required in patients with renal insufficiency.
About 95% of gliclazide is bound to plasma proteins, mostly to albumin.
14C-labelled tracer studies in rats have shown that gliclazide, given orally or intravenously, tends to concentrate in the liver and kidneys and some was also found in the pancreas and adrenals but very little in the central nervous system. No studies have reported its presence in the human breast milk.
Gliclazide is extensively metabolised by oxidation (its metabolites have no hypoglycaemic activity), and less than 20% is excreted in the urine unchanged.
The major route of elimination of gliclazide and its metabolites is via the urine.
There are no findings from chronic toxicity investigations suggesting that any side effects unknown to date could occur in humans.
Furthermore, in vivo and in vitro studies did not yield any indication of potential mutagenicity. Carcinogenicity studies have not been done.
No teratogenic changes have been shown in animal studies, but foetotoxic effects were present under treatment with gliclazide.
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