Pharmacokinetics of glibenclamide and its metabolites in diabetic patients with impaired renal function

Abstract

The differences in AUC, Cmax and CL/f of Gb may be explained by a higher free fraction in the IRF group which would increase Gb metabolic clearance. The inverse findings regarding M1 may be explained by the fact that the metabolites are primarily eliminated by the kidneys. After a single dose of Gb, neither Gb, M1 nor M2 seemed to accumulate in diabetic subjects with IRF. As only small amounts of M1 and M2 were excreted in the urine, this indicates one or several complementary non-renal elimination routes, e.g. shunting of metabolised Gb to the biliary excretion route and/or enterohepatic recycling of both metabolites and unmetabolised Gb.

Chronic Glibenclamide Treatment Attenuates Walker-256 Tumour Growth in Prediabetic Obese Rats

“…Tumour cells were grafted 24 h after the last dose of Gli treatment, which implies that no traces of the antihyperglycaemic drug could be found in the blood stream of the rats. According to other studies, the Gli plasma elimination half-life, after oral administration of multiple dosages, is approximately 15 h [31], indicating that Gli could protect the organism against tumour growth.…”

Lineamientos para el control de la glucemia y albuminuria en pacientes con nefropatía diabética en primer y segundo nivel de atención en Colombia. Panel nacional de expertos

“…Las sulfonilureas de primera generación están asociadas con hipoglucemia en pacientes con insuficiencia renal, dado que el mecanismo de excreción se hace por esta vía, por lo que no se recomienda su uso en estos individuos. Las sulfonilureas de segunda generación como glibenclamida están contraindicadas en pacientes con TFG < 60 ml/min/ 1.73 m 2 , y en pacientes con TFG mayor debe monitorearse constantemente el nivel de glucosa, pues existe riesgo de hipoglucemia; glimepirida y glicazida pueden administrarse en pacientes con TFG > 30 ml/min/1.73 m 2 con ajuste de dosis y se deben evitar en pacientes con TFG menor de este valor 7,26,29,30 .…”

The mechanism of action of oral antidiabetic drugs: A review of recent literature

“…10,11 Gliclazide (Diamicron) also has a duration of action of 12 -24 hours, but up to 65% of active metabolites are excreted mainly by the kidneys. 12 Glimepiride has a duration of action of about 24 hours and is eliminated by the liver.…”

“…It is not advisable to use these drugs once the glomerular filtration rate (GFR) falls to below 40 ml/min. 8,11 It is important to note that the receptor-specific binding characteristics of all the different sulphonylureas differ. Concern has been expressed that these drugs may aggravate angina symptoms in diabetic patients with existing coronary artery disease (CAD).…”