Glibenclamide

494.00400

494.00

233-570-6

SX6K58TVWC

759618

DTXSID0037237

C29076

A10BB01|A - Alimentary tract and metabolism

2935009090

121.98000

5.89520

Solid

1.36 g/cm3

169 °C

1.628

2.06e-03 g/L

2-8ºC

LD50 in rats and mice (g/kg): >20 orally; >12.5 i.p.; >20 s.c. (Mizukami)

204.7 Ų [M+H]+ [CCS Type: TW, Method: Major Mix IMS/Tof Calibration Kit (Waters)]|205.9 Ų [M+H]+ [CCS Type: TW, Method: calibrated with polyalanine and drug standards]

2

R20/21/22

22-36/37/39

YS4725200

Xn

Stable at normal temperatures and pressures.

P264, P270, P273, P301+P312, P330, P501

H302

|Warning|H302 (96.38%): Harmful if swallowed [Warning Acute toxicity, oral]|P264, P270, P273, P301+P312, P330, and P501|Aggregated GHS information provided by 222 companies from 10 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

The oral LD50 in rats is >3200mg/kg, in mice is >1500mg/kg, in rabbits is >10,000mg/kg, and in guinea pigs is >1500mg/kg. Patients experiencing an overdose may present with hypoglycemia. Mild hypoglycemia should be treated with oral glucose and adjustments to drug doses or meal schedules. Severe hypoglycemia may present with coma, seizure, and neurological impairment. This should be treated immediately in hospital with intravenous glucose and monitoring for 24-48 hours.

Glyburide is 99.9% bound to protein in plasma with >98% accounted for by binding to serum albumin.

Glyburide is indicated alone or as part of combination product with metformin, as an adjunct to diet and exercise, to improve glycemic control in adults with type 2 diabetes mellitus.|Amglidia is indicated for the treatment of neonatal diabetes mellitus, for use in newborns, infants and children.Sulphonylureas like Amglidia have been shown to be effective in patients with mutations in the genes coding for the β-cell ATP-sensitive potassium channel and chromosome 6q24-related transient neonatal diabetes mellitus.|Treatment of neonatal diabetes mellitus|Treatment of large hemispheric infarction

Glyburide is a second generation sulfonylurea that stimulates insulin secretion through the closure of ATP-sensitive potassium channels on beta cells, raising intracellular potassium and calcium ion concentrations. Glibenclamide has a long duration of action as it is given once daily, and a wide therapeutic index as patients are started at doses as low as 0.75mg but that can increase as high as 10mg or more. Patients taking glyburide should be cautioned regarding an increased risk of cardiovascular mortality as seen with tolbutamide, another sulfonylurea.

Substances which lower blood glucose levels. (See all compounds classified as Hypoglycemic Agents.)

Elderly patients taking glyburide reached a C_max of 211-315ng/mL with a T_max of 0.9-1.0h, while younger patients reached a C_max of 144-302ng/mL with a T_max of 1.3-3.0h. Patients taking glyburide have and AUC of 348ng*h/mL.|Unlike other sulfonylureas, glyburide is 50% excreted in the urine and 50% in the feces. Glyburide is mainly excreted as the metabolite 4-trans-hydroxyglyburide.|Elderly patients have a volume of distribution of 19.3-52.6L, while younger patients have a volume of distribution of 21.5-49.3L.|Elderly patients have a clearance of 2.70-3.55L/h, while younger patients have a clearance of 2.47-4.11L/h.

Glyburide is metabolized mainly by CYP3A4, followed by CYP2C9, CYP2C19, CYP3A7, and CYP3A5. These enzymes metabolize glyburide to 4-trans-hydroxycyclohexyl glyburide (M1), 4-cis-hydroxycyclohexyl glyburide (M2a), 3-cis-hydroxycyclohexyl glyburide (M2b), 3-trans-hydroxycyclohexyl glyburide (M3), 2-trans-hydroxycyclohexyl glyburide (M4), and ethylhydroxycyclohexyl glyburide (M5). The M1 and M2b metabolites are considered active, along with the parent molecule.|Glyburide has known human metabolites that include 2-trans-hydroxycyclohexyl glyburide, 3-cis-Hydroxycyclohexyl glyburide, 3-trans-Hydroxycyclohexyl glyburide, and 4-cis-hydroxycyclohexyl glyburide.

Elderly patients have a terminal elimination half life of 4.0-13.4h, while younger patients have a terminal elimination half life of 4.0-13.9h.

Glyburide belongs to a class of drugs known as sulfonylureas. These drugs act by closing ATP-sensitive potassium channels on pancreatic beta cells. The ATP-sensitive potassium channels on beta cells are known as sulfonylurea receptor 1 (SUR1). Under low glucose concentrations, SUR1 remains open, allowing for potassium ion efflux to create a -70mV membrane potential. Normally SUR1 closes in response to high glucose concentrations, the membrane potential of the cells becomes less negative, the cell depolarizes, voltage gated calcium channels open, calcium ions enter the cell, and the increased intracellular calcium concentration stimulates the release of insulin containing granules. Glyburide bypasses this process by forcing SUR1 closed and stimulating increased insulin secretion.

Daonil

Human drugs -> Orphan -> Amglidia -> EMA Drug Category|Drugs used in diabetes -> Human pharmacotherapeutic group|Human drugs -> Rare disease (orphan)|Human Drugs -> EU pediatric investigation plans|Human Drugs -> FDA Approved Drug Products with Therapeutic Equivalence Evaluations (Orange Book) -> Active Ingredients