| Indication |
For use as an adjunct to diet for the control of hyperglycemia and
its associated symptomatology in patients with non-insulin-dependent
diabetes mellitus (NIDDM; type II), formerly known as maturity-onset
diabetes, after an adequate trial of dietary therapy has proved
unsatisfactory. |
| Pharmacodynamics |
Glipizide, a second-generation sulfonylurea, is used with diet
to lower blood glucose in patients with diabetes mellitus type II. The
primary mode of action of glipizide in experimental animals appears to
be the stimulation of insulin secretion from the beta cells of
pancreatic islet tissue and is thus dependent on functioning beta cells
in the pancreatic islets. In humans glipizide appears to lower the blood
glucose acutely by stimulating the release of insulin from the
pancreas, an effect dependent upon functioning beta cells in the
pancreatic islets. In man, stimulation of insulin secretion by glipizide
in response to a meal is undoubtedly of major importance. Fasting
insulin levels are not elevated even on long-term glipizide
administration, but the postprandial insulin response continues to be
enhanced after at least 6 months of treatment. Some patients fail to
respond initially, or gradually lose their responsiveness to
sulfonylurea drugs, including glipizide. |
| Mechanism of action |
Sulfonylureas likely bind to ATP-sensitive potassium-channel
receptors on the pancreatic cell surface, reducing potassium conductance
and causing depolarization of the membrane. Depolarization stimulates
calcium ion influx through voltage-sensitive calcium channels, raising
intracellular concentrations of calcium ions, which induces the
secretion, or exocytosis, of insulin. |
| Absorption |
Gastrointestinal absorption is uniform, rapid, and essentially complete. |
| Volume of distribution |
|
| Protein binding |
98-99%, primarily to albumin. |
| Metabolism |
Hepatic. The major metabolites of glipizide are products of
aromatic hydroxylation and have no hypoglycemic activity. A minor
metabolite which accounts for less than 2% of a dose, an
acetylaminoethyl benzine derivatives, is reported to have 1/10 to 1/3 as
much hypoglycemic activity as the parent compound. |
| Route of elimination |
The primary metabolites are inactive hydroxylation products and polar conjugates and are excreted mainly in the urine. |
| Half life |
2-5 hours |
| Clearance |
Not Available |
| Toxicity |
The acute oral toxicity was extremely low in all species tested
(LD50 greater than 4 g/kg). Overdosage of sulfonylureas including
glipizide can produce hypoglycemia. |
