indication

Indicated as an adjunct to diet to lower the blood glucose in patients with NIDDM whose hyperglycemia cannot be satisfactorily controlled by diet alone.

pharmacology

Glyburide, a second-generation sulfonylurea antidiabetic agent, lowers blood glucose acutely by stimulating the release of insulin from the pancreas, an effect dependent upon functioning beta cells in the pancreatic islets. With chronic administration in Type II diabetic patients, the blood glucose lowering effect persists despite a gradual decline in the insulin secretory response to the drug. Extrapancreatic effects may be involved in the mechanism of action of oral sulfonyl-urea hypoglycemic drugs. The combination of glibenclamide and metformin may have a synergistic effect, since both agents act to improve glucose tolerance by different but complementary mechanisms. In addition to its blood glucose lowering actions, glyburide produces a mild diuresis by enhancement of renal free water clearance. Glyburide is twice as potent as the related second-generation agent glipizide.

mechanism of action

Sulfonylureas such as glyburide bind to ATP-sensitive potassium channels on the pancreatic cell surface, reducing potassium conductance and causing depolarization of the membrane. Depolarization stimulates calcium ion influx through voltage-sensitive calcium channels, raising intracellular concentrations of calcium ions, which induces the secretion, or exocytosis, of insulin.

toxicity

Oral rat LD₅₀: > 20,000 mg/kg. Oral mouse LD₅₀: 3250 mg/kg.

biotransformation

Primarily hepatic (mainly cytochrome P450 3A4). The major metabolite is the 4-trans-hydroxy derivative. A second metabolite, the 3-cis-hydroxy derivative, also occurs. These metabolites do not contribute clinically significant hypoglycemic action in humans as they are only weakly active; however, retention of 4-trans-hydroxyglyburide may prolong the hypoglycemic effect of the agent in those with severe renal impairment.

absorption

Significant absorption within 1 hour and peak plasma levels are reached in 2 to 4 hours. Onset of action occurs within one hour.

half life

1.4-1.8 hours (unchanged drug only); 10 hours (metabolites included). Duration of effect is 12-24 hours.

route of elimination

Glyburide is excreted as metabolites in the bile and urine, approximately 50% by each route. This dual excretory pathway is qualitatively different from that of other sulfonylureas, which are excreted primarily in the urine.

drug interactions

Acebutolol: Acebutolol may decrease symptoms of hypoglycemia and increase the time required for the body to compensate for hypoglycemia.

Acetylsalicylic acid: Acetylsalicylic acid increases the effect of the sulfonylurea, glibenclamide.

Atenolol: The beta-blocker, atenolol, may decrease symptoms of hypoglycemia.

Betaxolol: The beta-blocker, betaxolol, may decrease symptoms of hypoglycemia.

Bevantolol: The beta-blocker, bevantolol, may decrease symptoms of hypoglycemia.

Bismuth Subsalicylate: The salicylate, bismuth subsalicylate, increases the effect of the sulfonylurea, glibenclamide.

Bisoprolol: The beta-blocker, bisoprolol, may decrease symptoms of hypoglycemia.

Bosentan: Increased risk of hepatic toxicity

Carteolol: The beta-blocker, carteolol, may decrease symptoms of hypoglycemia.

Carvedilol: The beta-blocker, carvedilol, may decrease symptoms of hypoglycemia.

Chloramphenicol: Chloramphenicol may increase the effect of sulfonylurea, glibenclamide.

Clofibrate: Clofibrate may increase the effect of sulfonylurea, glibenclamide.

Colesevelam: Colesevelam may decrease the serum concentration of Glyburide. Glyburide should be administered at least 4 hours before colesevelam to minimize the risk of an interaction.

Cyclosporine: The sulfonylurea, glibenclamide, may increase the effect of cyclosporine.

Diazoxide: Antagonism.

Dicumarol: Dicumarol may increase the effect of sulfonylurea, glibenclamide.

Esmolol: The beta-blocker, esmolol, may decrease symptoms of hypoglycemia.

Glucosamine: Possible hyperglycemia

Labetalol: The beta-blocker, labetalol, may decrease symptoms of hypoglycemia.

Magnesium salicylate: The salicylate, magnesium salicylate, increases the effect of the sulfonylurea, glibenclamide.

Metoprolol: The beta-blocker, metoprolol, may decrease symptoms of hypoglycemia.

Nadolol: The beta-blocker, nadolol, may decrease symptoms of hypoglycemia.

Oxprenolol: The beta-blocker, oxprenolol, may decrease symptoms of hypoglycemia.

Penbutolol: The beta-blocker, penbutolol, may decrease symptoms of hypoglycemia.

Phenylbutazone: Phenylbutazone increases the effect of the hypoglycemic agent

Pindolol: The beta-blocker, pindolol, may decrease symptoms of hypoglycemia.

Practolol: The beta-blocker, practolol, may decrease symptoms of hypoglycemia.

Propranolol: The beta-blocker, propranolol, may decrease symptoms of hypoglycemia.

Rifampin: Rifampin may decrease the effect of sulfonylurea, glibenclamide.

Salicylate-sodium: The salicylate, salicylate-sodium, increases the effect of the sulfonylurea, glibenclamide.

Salsalate: The salicylate, salsalate, increases the effect of the sulfonylurea, glibenclamide.

Somatropin recombinant: Somatropin may antagonize the hypoglycemic effect of glibenclamide. Monitor for changes in fasting and postprandial blood sugars.

Sotalol: The beta-blocker, sotalol, may decrease symptoms of hypoglycemia.

Timolol: The beta-blocker, timolol, may decrease symptoms of hypoglycemia.

Trisalicylate-choline: The salicylate, trisalicylate-choline, increases the effect of the sulfonylurea, glibenclamide.