Absorption, Distribution and Excretion
Acetohexamide is rapidly absorbed via the gastrointestinal tract. The maximum hypoglycemic effect is observed approximately 3 hours after ingestion. The duration of action is 12-24 hours. Most of the activity is attributed to the metabolite hydroxyhexamide, which has a plasma half-life of approximately 6 hours; Acetohexamide has a plasma half-life of 1.3 hours. In individuals with normal renal and hepatic function, over 80% of the drug is excreted within 24 hours, primarily as metabolites. Peak plasma concentration time after oral administration: 3 hours (data from table)... Five days after oral administration... In rats, 86% of the drug was excreted in urine within 24 hours and 9% in feces within 48 hours. Results show rapid absorption and excretion... For more complete data on the absorption, distribution, and excretion of Acetohexamide (8 metabolites), please visit the HSDB record page.

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Metabolism/Metabolites
Acetohexamide is extensively metabolized in the liver to the active metabolite hydroxyhexamide, which has a stronger hypoglycemic effect than Acetohexamide. Hydroxyhexamide is considered to be the cause of the prolonged hypoglycemic effect.
Hydroxyhexamide…the major metabolite of Acetohexamide…is in the L-configuration in humans. …significantly promotes hypoglycemic response after administration…
Main metabolic degradation pathway in humans…reduction of P-acetyl to /1-[(P-α-hydroxyethylbenzene)sulfonyl]-3-cyclohexylurea, which has shown hypoglycemic effects in both humans and animals. And…may prolong the hypoglycemic activity of orally administered Acetohexamide.
Sulfonylureas are rapidly absorbed from the gastrointestinal tract, transported in the blood as highly protein-bound complexes, and undergo extensive hepatic metabolism (except for chlorpropamide). The hepatic metabolism and residual clearance of sulfonylureas vary considerably, and these factors often alter steady-state serum concentrations. Metabolites may be active, therefore there may be differences between the plasma half-life of the parent drug and the degree of hypoglycemia that occurs. /Sulfonylureas/
The concentration of active metabolites is higher than that of the parent drug. Some metabolites are excreted via the kidneys. /From Table/

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Biological Half-Life
The elimination half-life of the parent compound is 1.3 hours, and the elimination half-life of the active metabolite is approximately 5-6 hours.
Half-life...3.5-11 hours/ /From Table/

Effects During Pregnancy and Lactation
◉ Overview of Use During Lactation
Acetylhexanoimide has been discontinued in the United States. Due to a lack of information regarding the use of acetylhexanoimide during lactation, alternative medications are recommended, especially for breastfed newborns or premature infants. Close monitoring for signs of hypoglycemia in breastfed infants, such as irritability, lethargy, feeding difficulties, seizures, cyanosis, apnea, or hypothermia, is necessary. If there is any concern, monitoring of the breastfed infant's blood glucose levels is recommended while the mother is on medication to lower blood glucose levels.
◉ Effects on Breastfed Infants
No published information found as of the revision date.
◉ Effects on Lactation and Breast Milk
No published information found as of the revision date.

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Protein binding rate
90%Interaction
Drugs that may increase the risk of hypoglycemia caused by sulfonylureas include other hypoglycemic agents, sulfonamides, propranolol, salicylates, phenylbutazone, probenecid, dicumarol, chloramphenicol, monoamine oxidase inhibitors, and alcohol.
Sulfonylureas
In diabetic patients without hepatic or renal impairment, co-treatment with phenbutazone did not alter the plasma half-life, but the half-life of its metabolite hydroxyhexylamide (also an effective hypoglycemic agent) was significantly prolonged.
Oral administration of acetylhexylamide (100 mg/kg) and phenformin (50 mg/kg) daily for 7 days, combined with intraperitoneal injection of diphenylhydantoin, restored thiamine levels.
Concurrent intravenous administration of salicylic acid (20 mg/kg) and acetylhexylamide (30 mg/kg) in dogs increased the renal clearance of the metabolite hydroxyhexylamide.
For more complete data on interactions of acetylhexylamides (19 in total), please visit the HSDB record page.

Acetohexamide is a white, fluffy crystalline powder with almost no odor. (NTP, 1992)
Acetohexamide is an N-sulfonamide drug with the structure urea, where one nitrogen atom has a hydrogen atom replaced by an acetylbenzenesulfonyl group, and the other nitrogen atom has a hydrogen atom replaced by a cyclohexyl group. It has hypoglycemic and insulin secretagogue effects. It is an N-sulfonamide drug belonging to the acetophenone class.
Acetohexamide is a sulfonylurea hypoglycemic drug that is metabolized in the liver to 1-hydrohexamide. Acetohexamide has been discontinued in the United States.
Acetohexamide is a medium-potency first-generation sulfonylurea hypoglycemic drug. Acetohexamide is metabolized in the liver to the active metabolite hydroxyhexamide.
A sulfonylurea hypoglycemic drug that is metabolized in the liver to 1-hydroxyhexamide.
Drug Indications

For the treatment of type 2 diabetes (adult-onset).

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Mechanism of Action
Sulfonylureas (such as Acetohexamide) bind to ATP-dependent K+ channels on the pancreatic β-cell membrane. This inhibits sustained hyperpolarization of potassium ions, leading to an increase in membrane potential. This depolarization opens voltage-gated Ca2+ channels. The increased intracellular calcium ion concentration leads to increased fusion of insulin granules with the cell membrane, thereby increasing proinsulin secretion.
Sulfonylureas stimulate insulin secretion from pancreatic islet tissue. …Sulfonylurea administration increases insulin concentration in the islets…/Sulfonylureas/
Currently, the mechanisms of action of sulfonylureas are considered to be diverse. 1. …Causes potassium permeability depolarization of the pancreatic β-cell membrane. This leads to the release of pre-formed insulin into the bloodstream, which mainly occurs in patients with non-insulin-dependent diabetes mellitus. 2. Reduces basal hepatic glucose output… 3. Increases insulin receptor binding… 4. Increases intracellular AMP levels… 5. Increases insulin secretion by inhibiting the release of glucagon and somatostatin from pancreatic α and δ cells. /Sulfonylureas/
Sulfonylureas lower blood glucose in patients with non-insulin-dependent diabetes mellitus (NIDDM) by directly stimulating the acute release of insulin from functional β cells in pancreatic tissue through an unknown mechanism. This mechanism involves sulfonylurea receptors on β cells. Sulfonylureas inhibit ATP-potassium channels and potassium ion efflux on the β cell membrane, leading to β cell membrane depolarization and calcium ion influx, calmodulin binding, kinase activation, and the release of insulin-containing granules via exocytosis, which acts similarly to glucose. Insulin is a hormone that lowers blood glucose and controls the storage and metabolism of carbohydrates, proteins, and fats. Therefore, sulfonylureas are only effective in patients whose pancreas is capable of producing insulin. /Sulfonylurea Antidiabetic Drugs/

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Therapeutic Uses
Hypoglycemic Agents
…Used to treat mild to moderate adult-onset nonketotic diabetes mellitus, especially in patients whose diabetes cannot be controlled by diet alone.
…May be suitable for patients who are allergic to insulin and unwilling or unable to undergo desensitization therapy or inject insulin.…Especially suitable for elderly diabetic patients with poor vision, living alone, and at risk of hypoglycemia due to inappropriate insulin dosage. /Oral Hypoglycemic Agents/
…It is the only drug with uricosuric effects, and some clinicians prefer to use it to treat diabetic patients with gout.
For more complete data on the therapeutic uses of acetylhexylamide (6 types), please visit the HSDB record page.

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Drug Warnings
Reported adverse reactions include hematologic reactions (leukopenia, agranulocytosis, thrombocytopenia, pancytopenia, and hemolytic anemia), skin reactions (rash, photosensitivity), gastrointestinal reactions (nausea, vomiting, rare bleeding), and hepatic reactions (elevated serum alkaline phosphatase, cholestatic jaundice).
Adverse reactions occur in a low rate and are reversible upon discontinuation.
Ineffective in adolescent-onset, unstable, or brittle diabetes mellitus; contraindicated in diabetic patients with acidosis, ketosis, severe infection, coma, severe trauma, or major surgery.
Use with caution in elderly patients and patients with renal disease. Has a significant uricosuric effect. /Excerpt from table/
For more complete data on drug warnings for Acetohexamide (17 in total), please visit the HSDB record page.

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Pharmacodynamics
Acetohexamide is a medium-potency first-generation oral sulfonylurea. It lowers blood sugar by stimulating pancreatic beta cells to secrete insulin and helping the body use insulin effectively. Because it primarily acts on pancreatic beta cells, this drug is only effective in the presence of functional pancreatic beta cells capable of producing insulin granules. Acetylhexylurea is one-third as potent as chlorpropamide and twice as potent as tolbutamide; however, equivalent doses of sulfonylureas can achieve similar blood sugar-lowering effects.

C15H20N2O4S

324.4

324.114

968-81-0

1989

White to off-white solid powder

1.3g/cm3

188-190° (GB 912789); mp 175-177° (Marshall)

1.581

4.072

2

4

4

22

498

0

VGZSUPCWNCWDAN-UHFFFAOYSA-N

InChI=1S/C15H20N2O4S/c1-11(18)12-7-9-14(10-8-12)22(20,21)17-15(19)16-13-5-3-2-4-6-13/h7-10,13H,2-6H2,1H3,(H2,16,17,19)

1-(4-acetylphenyl)sulfonyl-3-cyclohexylurea

Acetohexamide Dymelor Dimelin DimelorAcetohexamidGamadiabet

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 : ~25 mg/mL (~77.07 mM)

Solubility in Formulation 1: 2.5 mg/mL (7.71 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 (7.71 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.)