Norizec Mechanism of Action

Pharmacology: Pharmacodynamics: Glimepiride is a sulfonylurea antidiabetic agent. It lowers blood glucose primarily by stimulating the release of endogenous insulin from functioning pancreatic β-cells. Glimepiride exerts its extrapancreatic effects in two ways: by increasing rapidly the number of active glucose transport molecules in the plasma membranes of the muscle and fat cells resulting in stimulated glucose uptake and by increasing the intracellular concentration of fructose-2,6-bisphosphate, resulting in the inhibition of glucose production in the liver (gluconeogenesis).
Pharmacokinetics: Glimepiride is completely (100%) absorbed from the gastrointestinal tract after oral administration. There was no change observed in the clearance of glimepiride at a dose range of 1 to 8 mg, exhibiting linear kinetics. Peak serum concentration is reached in about 2 to 3 hours. The time to reach C_max (T_max) was slightly increased (12%) and the mean C_max and AUC were slightly decreased (8% and 9%, respectively) when glimepiride was given with meals.
Glimepiride has a very low volume of distribution (about 8.8 L), high protein binding (>99.5%), and low total body clearance (approximately 48 mL/min). It is likely to be only minimally removed by hemodialysis. Glimepiride is excreted in milk in animals. It is transferred to the placenta and passage of the blood-brain barrier is low. There was no relevant accumulation of glimepiride in the blood.
Glimepiride is completely metabolized by oxidative biotransformation with cyclohexyl hydroxyl methyl derivative (M1) and carboxyl derivative (M2) as major metabolites. Cytochrome P450 2C9 has been shown to be involved in the biotransformation of glimepiride to M1 which has one-third the pharmacologic activity of its parent compound. However, it is not clear whether the glucose-lowering effect of M1 is clinically significant.
About 60% of glimepiride is recovered in the urine within 7 days with M1 (predominant) and M2 accounting for 80-90% of that recovered. About 40% is recovered in the feces; M1 and M2 (predominant) account for 70% of that recovered in the feces. No parent drug is recovered from urine or feces. The terminal half-lives of these metabolites were 3-6 and 5-6 hours, respectively. Significant biliary excretion of glimepiride or its M1 metabolite is not observed after IV dosing.