Sugril Mechanism of Action

Pharmacology: Pharmacodynamics: Glibenclamide is a sulfonylurea antidiabetic agent (second generation). Glibenclamide appears to lower blood glucose concentration principally by stimulating secretion of insulin from beta cells of the pancreas, an effect dependent upon functioning beta cells. Glibenclamide reduces glucose output from the liver and increases insulin sensitivity at peripheral target sites. In addition to its blood glucose lowering actions, Glibenclamide produces a mild diuresis by enhancement of renal free water clearance.
Pharmacokinetics: Absorption: Glibenclamide is readily absorbed from the gastrointestinal tract and peak plasma concentrations usually occur within 2 to 4 hours. Serum insulin levels begin to increase 15-60 minutes after a single dose. The hypoglycemic action may persist for up to 24 hours. Food apparently does not affect the absorption of Glibenclamide.
Distribution: In vitro, Glibenclamide is more than 99% bound to serum proteins and its major metabolite, 4-trans-hydroxyglibenclamide, is more than 97% bound to serum proteins. The protein binding of Glibenclamide is principally nonionic. Glibenclamide does not accumulate.
Metabolism: Glibenclamide appears to be completely metabolized in the liver. The drug is metabolized at the cyclohexyl ring principally to 4-trans-hydroxyglibenclamide. Glibenclamide is also metabolized to the 3-cis-hydroxy derivative. The hypoglycemic activity of Glibenclamide metabolites is generally considered clinically unimportant.
Excretion: About 50% of a dose is excreted in the urine and 50% via the bile into feces. The terminal half-life has averaged about 10 hours.