Glibenclamide

Class Oral hypoglycaemic
Chemistry

Second generation sulfonylurea

Routes of administration

Oral only

Absorption

Absorption can be rapid and complete with appropriate solubilising excipients. If it were absorbed completely, it would have 95% oral bioavailability, as only 5% is lost to first pass metabolism.

Solubility

pKa=5.5; terrible solubility in either water or lipid

Distribution

VOD= 0.2-0.45 L/kg; 99.9% protein bound

Metabolism

Extensive hepatic metabolism; two major metabolites are also active

Elimination

Weakly active metabolites are excreted in urine (50%) and in faeces (50%) via bile

Time course of action

Half life 15 hrs

Target receptor

Sulfonylurea receptors (SUR1 and SUR2), which form a part of the ATP-sensitive potassium channel complex on pancreatic β-cells

Mechanism of action

By binding to the ATP-sensitive K channel, sulfonylureas act like ATP (i.e. same as a rise in blood glucose), closing the channel and stopping the efflux of potassium from the cell, which promotes depolarisation. The depolarisation then leads to insulin release

Clinical effects

Hypoglycaemia, but also:
- undesirable severe hypoglycaemia
- hypokalemia
- secondary failure of therapy (as beta-cells burn out)
- erythema multiforme
- exfoliative dermatitis
- photosensitivity

Literature reference

Coppack, 1990

CICM details of understanding Level 3
Mentioned around Deranged Physiology
Related SAQs