In primary mouse pancreatic beta cells, glipizide inhibits ATP-sensitive potassium (KATP) channels (IC50= 6.4 nM) [1].

Absorption, Distribution and Excretion
Glipizide is absorbed uniformly, rapidly, and substantially completely from the gastrointestinal tract. In patients with type 2 diabetes, the absolute bioavailability of glipizide is 100% after a single oral dose. Peak plasma concentrations are expected to be reached within 6 to 12 hours after the first dose. Steady-state plasma concentrations of glipizide in extended-release oral formulations are maintained over a 24-hour dosing interval. In healthy volunteers, the presence of food delays the absorption of glipizide but does not affect total absorption. Glipizide is primarily eliminated via hepatic biotransformation; less than 10% of the initial dose is present in unchanged form in urine and feces. Approximately 80% of the metabolites of glipizide are excreted in urine and 10% in feces. In patients with type 2 diabetes, the mean volume of distribution after a single intravenous administration is approximately 10 liters. In mouse and rat studies, the levels of the drug and its metabolites in pregnant female fetuses were very low or absent. Other sulfonylureas have been shown to cross the placenta into breast milk, therefore the potential risk of glipizide to the fetus or infant cannot be ruled out. In patients with type 2 diabetes, the mean systemic clearance of glipizide after a single intravenous administration is approximately 3 liters/hour. Metabolites/Metabolites Glipizide is primarily metabolized in the liver, and its major metabolites are formed by aromatic hydroxylation. These major metabolites have been reported to be pharmacologically inactive. In contrast, acetaminoethylbenzene derivatives, a minor metabolite present in less than 2% of the initial dose, have been reported to have only one-tenth to one-third the hypoglycemic activity of the parent compound. Known metabolites of glipizide include 4-trans-hydroxyglipizide. Primarily metabolized in the liver. The major metabolite of glipizide is an aromatic hydroxylation product, which has no hypoglycemic activity. A minor metabolite present in less than 2%, namely acetaminoethylbenzene derivatives, has been reported to have only one-tenth to one-third the hypoglycemic activity of the parent compound. Elimination pathway: The main metabolites are inactive hydroxylated products and polar conjugates, primarily excreted in the urine. Half-life: 2-5 hours. In patients with type 2 diabetes, the mean terminal elimination half-life of glipizide is 2 to 5 hours after single or multiple administrations.

Toxicity Summary
Sulfonylureas may bind to ATP-sensitive potassium channel receptors on the surface of pancreatic cells, reducing potassium conductance and causing cell membrane depolarization. Depolarization stimulates calcium ion influx through voltage-sensitive calcium channels, increasing intracellular calcium concentration and thus inducing insulin secretion (exocytosis). Pregnancy and Lactation Effects ◉ Overview of Use During Lactation Limited data suggest low concentrations of glipizide in breast milk. However, especially in breastfed newborns or preterm infants, alternative medications with more comprehensive information may be preferred. Breastfed infants should be monitored for signs of hypoglycemia, such as irritability, lethargy, feeding difficulties, seizures, cyanosis, apnea, or hypothermia. If in any concern, monitoring of blood glucose levels in breastfed infants is recommended while the mother is taking hypoglycemic agents. ◉ Effects on Breastfed Infants Two breastfed infants whose mothers took 5 mg of glipizide daily had normal blood glucose levels.
◉ Effects on lactation and breast milk
As of the revision date, no relevant published information was found.

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Protein binding
Glipizide binds to serum proteins at a rate of approximately 98-99%, with albumin being the predominant plasma protein.

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Toxicity data
Acute oral toxicity was extremely low in all tested species (LD50 > 4 g/kg).

[1]. Concentration-dependent effects of tolbutamide, meglitinide, glipizide, glibenclamide and diazoxide on ATP-regulated K+ currents in pancreatic B-cells. Naunyn Schmiedebergs Arch Pharmacol. 1988 Feb;337(2):225-30.

[2]. Glipizide. From Wikipedia.

Pharmacodynamics
Glipizide is a hypoglycemic agent. It begins to take effect approximately 30 minutes after administration, and its hypoglycemic effect lasts for about 12 to 24 hours. While long-term use of glipizide does not lead to elevated fasting insulin levels, postprandial insulin response (i.e., the insulin response after meals) is enhanced, even after 6 months of treatment. Glipizide's primary therapeutic effect occurs in the pancreas, stimulating insulin release, but it also has some extrapancreatic effects, such as enhancing insulin signaling effects on muscle, fat, or hepatocytes. Due to its effects on endogenous cells, sulfonylureas, including glipizide, increase the risk of hypoglycemia and weight gain. Long-term use of glipizide may lead to downregulation of sulfonylurea receptors on pancreatic β-cells, which are the molecular targets of the drug, thereby reducing insulin secretion. Like other sulfonylureas, glipizide may act on pancreatic δ-cells and α-cells, stimulating somatostatin secretion and inhibiting glucagon secretion. Somatostatin and glucagon are both peptide hormones that regulate neuroendocrine and metabolic pathways. In addition to its primary effects on the pancreas, glipizide also has other biological effects outside the pancreas, known as "exopancreatic effects," similar to other sulfonylureas. Glipizide can enhance glucose uptake in skeletal muscle and enhance hepatic insulin action. Other effects include inhibiting lipolysis in the liver and adipose tissue, inhibiting hepatic glucose output, and increasing glucose uptake and oxidation. Multiple studies have also shown that long-term use of sulfonylureas may lead to an increase in insulin receptor expression on monocytes, adipocytes, and erythrocytes.

C21H27N5O4S

445.54

445.178

29094-61-9

Glipizide-d11;1189426-07-0

3478

White to off-white solid powder

1.4±0.1 g/cm3

676.0±65.0 °C at 760 mmHg

208-209°C

362.6±34.3 °C

0.0±2.2 mmHg at 25°C

1.654

3.37

3

6

7

31

697

0

ZJJXGWJIGJFDTL-UHFFFAOYSA-N

InChI=1S/C21H27N5O4S/c1-15-13-24-19(14-23-15)20(27)22-12-11-16-7-9-18(10-8-16)31(29,30)26-21(28)25-17-5-3-2-4-6-17/h7-10,13-14,17H,2-6,11-12H2,1H3,(H,22,27)(H2,25,26,28)

N-[2-[4-(cyclohexylcarbamoylsulfamoyl)phenyl]ethyl]-5-methylpyrazine-2-carboxamide

Minidiab; Glucotrol; Glipizide

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO : ~50 mg/mL (~112.22 mM)
H2O : ~0.67 mg/mL (~1.50 mM)

Solubility in Formulation 1: 2.5 mg/mL (5.61 mM) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: ≥ 2.5 mg/mL (5.61 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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 (Please use freshly prepared in vivo formulations for optimal results.)