글리클라지드

Pharmaceuticals

Pharmaceuticals -> Used in Switzerland

1.90e-01 g/L

42.6 [ug/mL] (The mean of the results at pH 7.4)

180-182

181 °C

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

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

This chemical does not meet GHS hazard criteria for 77.5% (55 of 71) of all reports.

Warning

H302 (12.7%): Harmful if swallowed [Warning Acute toxicity, oral]

P203, P264, P270, P280, P301+P317, P318, P330, P405, and P501 (click each P-code to see the statement)

Aggregated GHS information provided per 71 reports by companies from 14 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

Drug-Induced Liver Injury Severity and Toxicity (DILIst)

Gliclazide

DILI Positive

Oral

DOI:10.1016/j.drudis.2019.09.022

A10BB09

A - Alimentary tract and metabolism

QA - Alimentary tract and metabolism

A10BB09

Based on the pharmacological properties, gliclazide is a second generation sulphonylurea which acts as a hypoglycemic agent. It stimulates β cells of the islet of Langerhans in the pancreas to release insulin. It also enhances peripheral insulin sensitivity. Overall, it potentiates insulin release and improves insulin dynamics.

Gliclazide binds to the β cell sulfonyl urea receptor (SUR1). This binding subsequently blocks the ATP sensitive potassium channels. The binding results in closure of the channels and leads to a resulting decrease in potassium efflux leads to depolarization of the β cells. This opens voltage-dependent calcium channels in the β cell resulting in calmodulin activation, which in turn leads to exocytosis of insulin containing secretorty granules.

Extensively metabolized in the liver. Less than 1% of the orally administered dose appears unchanged in the urine. Metabolites include oxidized and hydroxylated derivates, as well as glucuronic acid conjugates.

Gliclazide has known human metabolites that include 6-hydroxy-gliclazide, 7-hydroxy-gliclazide, and Methylhydroxygliclazide.

Rapidly and well absorbed but may have wide inter- and intra-individual variability. Peak plasma concentrations occur within 4-6 hours of oral administration.