Glibenclamide metabolites

Glibenclamide has an intermediate duration of action. It is well absorbed with peak levels 4 hours after oral dosing. Its protein binding is about 90%. Glibenclamide is metabolized in the liver with an elimination half-life of 10 hours. However some of the metabolites which are excreted in the urine have hypoglycemic activity which makes glibenclamide... 

Glyburide (DiaBeta, Micronase, Glynase), also known as glibenclamide, is approximately 150 times as potent as tolbutamide on a molar basis and twice as potent as glipizide (discussed later). Glyburide is completely metabolized in the liver to two weakly active metabolites before excretion in the urine. Its average duration of action is 24 hours. 

In the second case, renal insufficiency could have reduced the clearance of the active metabolites of glibenclamide. 

Ultrafiltration has been used to determine the protein bound fraction of many drags, such as methadone (Wilkins et al. 1997), phenylacetate and phenylbu-tyrate (Boudoulas et al. 1996), etoposide (Robieux et al. 1997), doxorubicin and vincristine (Mayer and St-Onge 1995), disopyramide (Echize et al. 1995), and ketamine and its active metabolites (Hijazi and Boulieu 2002). Schumacher et al. (2000) have shown the applicability for the determination of erythro-cyte/plasma distribution. The method of UF has been applied in the measurement of free unaltered thyroxin or after displacement by salicylate as well after displacement by heparin in healthy people and in patients with non-thyroidal somatic illness (Faber et al. 1993). The protein binding of tritium labeled, antidiabetic repaglinide and its displacement by warfarin, furosemide, tolbutamide, diazepam, glibenclamide and nicardipine were determined by ultrafiltration (Plumetal. 2000). 

Glibenclamide 4-trans-Hydroxyglibendamide (a) 3-c/s-Hydroxyglibenclamide (i) One unidentified metabolite (i)... 

Reactive hyperemia is the increased blood flow over normal values that is seen following a period of interruption of flow. Reactive hyperemia is attenuated by glibenclamide in both coronary and skeletal muscle vascular beds, suggesting a role of K xp channels in this phenomenon (Clayton et al., 1992). Activation of K xp channels under these conditions may occur through a buildup of vasodilator metabolites (e.g., adenosine) during the period of occlusion. 

Rydberg, T. WShlin-Boll, E. Melander, A. Determination of glibenclamide and its two megor metabolites in hvunan serum and urine by column liquid chromatography. J.Chromatogr., 1991, 564, 223-233... 

Forist AA and Chulski T, pH-solubility relations for l-butyl-3-(p-tolylsulfonyl)urea (Orinase) and its metabolite, l-butyl-3-(p-carboxyphenylsulfonyl)urea. Metabolism, 5, 807-812 (1956). NB The metabolite was found to have pJCa = 3.54 at 37.5 °C by the solubility medrod. See also Glibenclamide for furdier discussion. See also Beyer WF, Jensen EH, Tolbutamide, APDS, 3,513-543 (1974). 

Parecoxib. Valdecoxib, the active metabolite of parecoxib, does not appear to affect either the pharmacokinetics of glibenclamide or its effects on insulin or blood glucose levels. ... 

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