GLIPIZIDE

Chemistry - A sulfonylurea antidiabetic agent, glipizide (also known as glydiazinamide) occurs asa whitish powder. It is practically insoluble in water and has pKa of 5.9.

Storage, Stability, Compatibility

Tablets should be stored in tight, light-resistant containers atroom temperature.

Pharmacology - GLIPIZIDE

Sulfonylureas lower blood glucose concentrations in both diabetic and non-diabetics. The exact mechanism of action is not known, but these agents are thought to exert the effect primarily by stimulating the Beta cells in the pancreas to secrete additional endogenous insulin.
Extrapancreatic effects include enhanced tissue sensitivity of circulating insulin. Ongoing use of thesulfonylureas appear to also enhance peripheral sensitivity to insulin and reduce the production ofhepatic basal glucose. The mechanisms causing these effects are yet to be fully explained, however.
Uses, Indications - Glipizide may be of benefit in treating cats with type II diabetes. It potentiallymay be useful in treating canine patients with type II or III diabetes as well, but somepharmacologists state that by the time dogs present with hyperglycemia, they are absolutely orrelatively insulinopenic and glipizide would probably be ineffective.

Pharmacokinetics - GLIPIZIDE

Glipizide is rapidly and practically completely absorbed after oral administration. The absolute bioavailability reported in humans ranges from 80-100%. Food will alter the rate but not the extent of absorption. Glipizide is very highly bound to plasma proteins. It is primarily biotransformed in the liver to inactive metabolites which are then excreted by the kidneys.
In humans, half life is about 2-4 hours. Effects on insulin levels in cats tend to be short-lived.
Effects peak in about 15 minutes and return to baseline after about 60 minutes.

Contraindications, Precautions, Reproductive Safety

Oral antidiabetic agents are consideredcontraindicated with the following conditions: severe burns, severe trauma, severe infection, diabeticcoma or other hypoglycemic conditions, major surgery, ketosis, ketoacidosis or other significantacidotic conditions. Glipizide should only be used when its potential benefits outweigh its risksduring untreated adrenal or pituitary insufficiency; thyroid, renal or hepatic function impairment;prolonged vomiting; high fever; malnourishment or debilitated condition is present.
Some patients with type II or type III diabetes may have their disease complicated by the production of excessive amounts of cortisol or growth hormone which may antagonize insulin's effects. These causes should be ruled out before initiating oral antidiabetic therapy.
Safe use during pregnancy has not been established. Glipizide was found to be mildly fetotoxic inrats when given at doses at 5-50 mg/kg. However, no other teratogenic effects were noted. Use inpregnancy only when benefits outweigh potential risks. It is unknown if glipizide enters milk.

Adverse Effects, Warnings

Experience with glipizide is limited in veterinary medicine. Somecats receiving this drug have reportedly developed hypoglycemia, vomiting, icterus and increased
ALT (SGPT) levels. Should toxicity develop, reinstitution of drug therapy may be attempted at alower dosage after sign/symptom resolution.
Other adverse effects that are possible (noted in humans) include: allergic skin reactions, bonemarrow suppression, or cholestatic jaundice.
Glipizide does not appear to be effective in cats demonstrating insulin resistance.

Overdosage, Acute Toxicity

Oral LD50's are greater than 4 g/kg in all animal species tested.
Profound hypoglycemia is the greatest concern after an overdose. Gut emptying protocols should be employed when warranted. Because of its shorter half life than chlorpropamide, prolonged hypoglycemia is less likely with glipizide, but blood glucose monitoring and treatment with parenteral glucose may be required for several days. Massive overdoses may also require additional monitoring (blood gases, serum electrolytes) and supportive therapy.

Drug Interactions

A disulfiram-like reaction (anorexia, nausea, vomiting) has been reported inhumans who have ingested alcohol within 48-72 hours of receiving glipizide.
The following drugs may displace glipizide, or be displaced by glipizide from plasma proteins, thereby causing enhanced pharmacologic effects of the two drugs involved: chloramphenicol, furazolidone, non-steroidal anti-inflammatory agents, salicylates, sulfonamides, warfarin.beta adrenergic blocking agents (e.g., propranolol) may affect diabetes (mellitus) control.
Glipizide may prolong the duration of action of barbiturates. Probenecid or monamine oxidase inhibitors may increase the hypoglycemic effects of glipizide.
Thiazide diuretics may exacerbate diabetes mellitus.
Cimetidine may potentiate the hypoglycemic effects of glipizide.