Glipizide Metabolism Half-Life
Glipizide has a relatively short half-life of 2-4 hours in normal subjects after either intravenous or oral administration, with metabolism occurring rapidly and extensively in the liver. 1
Pharmacokinetic Profile of Glipizide
Absorption and Distribution
- Gastrointestinal absorption is uniform, rapid, and essentially complete
- Peak plasma concentrations occur 1-3 hours after a single oral dose
- Protein binding is very high at 98-99% one hour after administration
- Apparent volume of distribution is approximately 11 liters after intravenous administration 1
Metabolism
Glipizide undergoes extensive metabolism primarily in the liver:
- The main metabolic pathways include:
- Formation of inactive hydroxylation products
- Creation of polar conjugates
- Less than 10% of unchanged glipizide is found in the urine 1
- The primary metabolites are pharmacologically inactive 2
Elimination
- Half-life ranges from 2-4 hours in subjects with normal renal function 1
- Some studies have reported a terminal elimination half-life range of 2-7 hours 3
- Metabolites are excreted mainly in the urine 1
Clinical Implications of Glipizide's Short Half-Life
Dosing Considerations
- Due to its short half-life, glipizide has a rapid onset of action
- The insulinotropic response to a meal occurs within 30 minutes after an oral dose
- Blood sugar control may persist in some patients for up to 24 hours despite the short half-life 1
- Most effective when administered approximately 30 minutes before meals 1
Special Populations
Patients with renal impairment:
- Glipizide is preferred over other sulfonylureas in patients with chronic kidney disease as it does not have active metabolites 4
- However, dosage should be initiated conservatively to avoid hypoglycemia 4
- Patients with renal impairment have a higher risk of developing severe hypoglycemia (odds ratio 4.0) 5
Elderly patients:
- Elderly patients (mean age 75 years) are at higher risk for severe hypoglycemia 5
- Careful dose adjustment is necessary in this population
Comparison to Other Sulfonylureas
- Glipizide has a shorter duration of action compared to glibenclamide (glyburide) 2
- Glyburide has a longer half-life of 7-10 hours compared to glipizide's 2-4 hours 3
- Unlike first-generation sulfonylureas (chlorpropamide, tolazamide, tolbutamide), glipizide does not rely on the kidney to eliminate both parent drug and active metabolites 4
Practical Considerations
- Despite its short half-life, glipizide can provide effective glycemic control with once or twice daily dosing
- Careful monitoring is important when initiating therapy, particularly in elderly patients or those with renal impairment
- Drug interactions should be considered, as patients taking multiple medications (particularly diuretics and benzodiazepines) have higher risk of hypoglycemia 5
In summary, glipizide is rapidly metabolized with a half-life of 2-4 hours, undergoes extensive hepatic metabolism to inactive metabolites, and is primarily excreted through the kidneys. This relatively short half-life contributes to its rapid onset of action but requires careful dosing to maintain glycemic control throughout the day.