Pharmacological properties : תכונות פרמקולוגיות

Pharmacodynamic Properties

5.1 Pharmacodynamic properties
Pharmacotherapeutic group: Drugs used in diabetes, blood glucose lowering drugs excl. insulins, sulfonylureas, ATC code: A10BB07.
Glipizide is an oral blood glucose lowering drug of the sulphonylurea class. The primary mode of action of glipizide is the stimulation of insulin secretion from the beta-cells of pancreatic islet tissue. Stimulation of insulin secretion by glipizide in response to a meal is of major importance. Fasting insulin levels are not elevated even on long-term glipizide administration, but the post-prandial insulin response continues to be enhanced after at least 6 months of treatment. The insulinotropic response to a meal occurs within 30 minutes after oral dose of glipizide in diabetic patients, but elevated insulin levels do not persist beyond the time of the meal challenge. There is also increasing evidence that extrapancreatic effects involving potentiation of insulin action form a significant component of the activity of glipizide.


Blood sugar control persists for up to 24 hours after a single dose of glipizide, even though plasma levels have declined to a small fraction of peak levels by that time (see section 5.2).

Pharmacokinetic Properties

5.2 Pharmacokinetic properties
Absorption
Gastrointestinal absorption of glipizide in hummans is uniform, rapid and essentially complete. Peak plasma concentrations occur 1to 3 hours after a single oral dose. The half-life of elimination ranges from 2to 4 hours in normal subjects, whether given intravenously or orally. The metabolic and excretory patterns are similar with the two routes of administration, indicating that first-pass metabolism is not significant. Glipizide does not accumulate in plasma on repeated oral administration. Total absorption and disposition of an oral dose were unaffected by food in normal volunteers, but absorption was delayed by about 40 minutes. Thus, glipizide was more effective when administered about 30 minutes before, rather than with, a test meal in diabetic patients.
Distribution
Protein binding was studied in serum from volunteers who received either oral or intravenous glipizide and found to be 98%to 99% one hour after either route of administration. The apparent volume of distribution of glipizide after intravenous administration was 11L, indicative of localisation within the extracellular fluid compartment. In mice, no glipizide or metabolites were detectable autoradiographically in the brain or spinal cord of males or females, nor in the foetuses of pregnant females. In another study, however, very small amounts of radioactivity were detected in the foetuses of rats given labelled drug.
Biotransformation
The metabolism of glipizide is extensive and occurs mainly in the liver.

Elimination
The primary metabolites are inactive hydroxylation products and polar conjugates and are excreted mainly in the urine. Less than 10% unchanged glipizide is found in urine.