Pharmacotherapeutic Group: Blood glucose lowering drugs, excl. insulins: sulfonamides, urea derivatives. ATC Code: A10BB12.
Pharmacology: Pharmacodynamics: 2 mg: Glimepiride is an anti-diabetic type 2 (noninsulin-dependent) agent belonging to the sulfonylurea group. Glimepiride acts mainly by stimulating insulin release from pancreatic beta cells, so the drug is effective only when the pancreas still works (also capable of releasing insulin). The mechanism of action of glimepiride is to bind to the receptors on beta cell membrane, leading to closure of the ATP-sensitive potassium channels. Closing the potassium channel induces depolarization of the beta cell and results - by opening of calcium channels - in an increase influx of calcium into the cell. The increase in intracellular calcium concentration stimulates insulin release from the cells. Like other sulfonylureas, glimepiride produces hypoglycemia in patients with diabetes or healthy people without diabetes. Using glimepiride and sulfonylureas for long term also causes some extrapancreatic effects which significantly contribute to hypoglycemia effects. The main extrapancreatic effects are an improvement of the sensitivity of the peripheral tissues for insulin and a decrease of the glucose production in the liver. Glimepiride also has synergistic effects with metformin or insulin.
4 mg: Glimepiride is a drug for the treatment of type 2 diabetes mellitus of the sulfonylurea class. The primary mechanism of action of glimepiride in lowering blood glucose appears to be dependent on stimulating the release of insulin from functioning pancreatic beta cells. In addition, extrapancreatic effects may also play an important role in the activity of sulfonylureas such as glimepiride, which increased sensitivity of peripheral tissues to insulin.
Pharmacokinetics: 2 mg: The bioavailability of glimepiride after oral administration is complete. Food intake has no relevant influence on absorption, only the absorption rate is slightly diminished. Maximum plasma concentrations are reached 2.5 hours after oral intake. Glimepiride has a very low distribution volume (approx. 8.8 litres), which is roughly equal to albumin distribution space, high protein binding (99%) and a low clearance (approx. 48 ml/min). Mean dominant plasma half-life is about 5 - 8 hours. After high doses, slightly longer half-lives were noted. After a single dose of radiolabelled glimepiride, 58% of the radioactivity was recovered in the urine, and 35% in the faeces. No unchanged substance was detected in the urine. Two metabolites most probably resulting from hepatic metabolism (major enzyme is CYP2C9) were identified both in urine and faeces: The hydroxy derivative and the caboxy derivative.
4 mg: Glimepiride is completely absorbed from the gastrointestinal tract. Peak plasma concentrations occur in 2 to 3 hours, and it is highly protein bound. The drug is extensively metabolised to two main metabolites, a hydroxy derivative and a carboxy derivative. The half-life after multiple doses is about 9 hours. Approximately 60% of a dose is eliminated in the urine and 40% in the faeces.