Glyset is an oral Sulfonylurea that contains the active ingredient Glimepiride. Chemically, Glimepiride is identified as 1-[p-12-(3-ethyl-4-methyl-2-oxo-3-pyrroline 1carboxamido) ethyllphenyl]sulfonyl]-3-(trans-4-methyl cyclohexyl) urea (C, HN, O, S) with a molecular weight of 490.62. Glimepiride is a white to yellowish-white, crystalline, odorless to practically odorless powder and is practically insoluble in water
MECHANISM OF ACTION
Glimepiride (Glyset) primarily lowers blood glucose by stimulating the release of Insulin from pancreatic beta cells. Sulfonylureas bind to the Sulfonylurea receptor in the pancreatic beta cell plasma membrane, leading to the closure of the ATP-sensitive Potassium channel, thereby stimulating the release of Insulin.
PHARMACOKINETICS
Absorption: Studies with single oral doses of Glimepiride (Glyset) in healthy subjects and with multiple oral doses in s in patients with type 2 diabetes showed peak drug concentrations (Cmax) 2 to 3 hours post-dose. When Glimepiride (Glyset) was given with meals, the mean Cmax and AUC (area under the curve) were decreased by 8% and 9%, respectively, Glimepiride does not accumulate in serum following multiple dosing. The pharmacokinetics of Glimepiride (Glyset) does not differ between healthy subjects and patients with type 2 diabetes. Clearance of Glimepiride after oral administration does not change over the 1mg to 4mg dose range, indicating linear pharmacokinetics. In healthy subjects, the intra and inter-individual variabilities of Glimepiride (Glyset) pharmacokinetic parameters were 15-23% and 24-29%, respectively. Distribution: Glimepiride has a very low distribution volume (approx. 8.8 liters), which is roughly equal to the Albumin distribution space, with high protein binding (>99%).
Metabolism: Glimepiride is completely metabolized by oxidative biotransformation after an oral dose. The primary metabolites are the Cyclohexyl hydroxy methyl derivative (M1) and the Carboxyl derivative (M2). Cytochrome P450 2C9 is involved in the biotransformation of Glimepiride to M1. M1 is further metabolized to M2 by one or several cytosolic enzymes. M2 is inactive. In animals, M1 possesses about one-third of the pharmacological activity of Glimepiride (Glyset), but it is unclear whether M1 results in clinically meaningful effects on blood glucose in humans.
Excretion: When “C Glimepiride was given orally to 3 healthy male subjects, approximately 60% of the total radioactivity was recovered in the urine in 7 days. M1 and M2 accounted for 80-90% of the radioactivity recovered in the urine. The ratio of M1 to M2 in the urine was approximately 3:2 in two subjects and 4:1 in one subject. Approximately 40% of the total radioactivity was recovered in feces, M1 and M2 accounted for approximately 70% (The ratio of M1 to M2 was 1:3) of the radioactivity recovered in feces. No parent drug was recovered from urine or feces.