| Indication |
For concomitant use with insulin for the treatment of noninsulin-dependent (type 2) diabetes mellitus. |
| Pharmacodynamics |
Glimepiride, like glyburide and glipizide, is a
"second-generation" sulfonylurea agents. Glimepiride is used with diet
to lower blood glucose by increasing the secretion of insulin from
pancreas and increasing the sensitivity of peripheral tissues to
insulin. |
| Mechanism of action |
The mechanism of action of glimepiride in lowering blood glucose
appears to be dependent on stimulating the release of insulin from
functioning pancreatic beta cells, and increasing sensitivity of
peripheral tissues to insulin. Glimepiride likely binds to ATP-sensitive
potassium channel receptors on the pancreatic cell surface, reducing
potassium conductance and causing depolarization of the membrane.
Membrane depolarization stimulates calcium ion influx through
voltage-sensitive calcium channels. This increase in intracellular
calcium ion concentration induces the secretion of insulin. |
| Absorption |
Completely (100%) absorbed following oral administration. |
| Volume of distribution |
- 21.8 ± 13.9 L [Volunteers]
- 19.8 ± 12.7 L [Patients with Type 2 diabetes, Single Dose]
- 37.1 ± 18.2 L [Patients with Type 2 diabetes, Multiple Dose]
|
| Protein binding |
Over 99.5% bound to plasma protein. |
| Metabolism |
Hepatic. Following either an intravenous or oral dose,
glimepiride is completely metabolized by oxidative biotransformation to a
major metabolite, cyclohexyl hydroxymethyl derivative (M1), via the
hepatic cytochrome P450 II C9 subsystem. M1 is further metabolized to
the carboxyl derivative (M2) by one or several cytosolic enzymes. M1,
but not M2, possessed approximately one third of the pharmacologic
activity of its parent in an animal model. However, whether the
glucose-lowering effect of M1 is clinically significant is not clear. |
| Route of elimination |
Not Available |
| Half life |
Approximately 5 hours following single dose. |
| Clearance |
- 52.1 +/- 16.0 mL/min [Normal subjects with single oral dose]
- 48.5 +/- 29.3 mL/min [Patients with Type 2 diabetes, with single oral dose]
- 52.7 +/- 40.3 mL/min [Patients with Type 2 diabetes, with multiple oral dose]
- 47.8 mL/min [healthy after intravenous (IV) dosing]
|
| Toxicity |
Severe hypoglycemic reactions with coma, seizure, or other neurological impairment. |
