グリベンクラミド

Pharmaceuticals

Pharmaceuticals -> Listed in ZINC15

4.7

3.09

Breast Feeding; Lactation; Milk, Human; Hypoglycemic Agents; Sulfonylurea Compounds

FDA approved drugs -> Active ingredient

EMA approved medicines: Human medicine (Orphan designations)

FDA approved drugs -> Active ingredient

213.2 Ų [M-H]- [CCS Type: DT; Buffer gas: N2; Ionization: ESI-; Dataset: TOXCAST; Source Identifier: DTXSID0037237]

204.7 Ų [M+H]+ [CCS Type: TW; Method: Major Mix IMS/Tof Calibration Kit (Waters)]

216.96 Ų [M+K]+ [CCS Type: TW; Method: calibrated with polyalanine and drug standards]

205.9 Ų [M+H]+ [CCS Type: TW; Method: calibrated with polyalanine and drug standards]

This chemical does not meet GHS hazard criteria for 1.1% (1 of 95) of reports.

Warning

H302 (89.5%): Harmful if swallowed [Warning Acute toxicity, oral]

P264, P270, P273, P301+P317, P330, and P501 (click each P-code to see the statement)

Aggregated GHS information provided per 95 reports by companies from 11 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

Glyburide toxicity is primarily associated with the risk of severe hypoglycemia due to an excessive dosage, whether it occurs accidentally or intentionally. Due to duplicate metabolism involving the CYP2C9 enzyme, drug-drug interactions between glyburide and other sulfonylureas can also potentiate hypoglycemia.

Drug Induced Liver Injury Rank (DILIrank 2.0)

Glyburide

vLess-DILI-concern

3

Adverse reactions

DOI:10.1016/j.drudis.2016.02.015

A10BB01

A - Alimentary tract and metabolism

QA - Alimentary tract and metabolism

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.

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.

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.