Absorption, Distribution and Excretion
After oral administration, the drug is well absorbed in the gastrointestinal tract. It is well absorbed in the gastrointestinal tract. It is distributed throughout the body fluids. Excretion: Kidneys – 36%–65% excreted unchanged; 9%–14% excreted as acetamide. Respiratory tract – 20%–40% excreted as carbon dioxide. In rodents, approximately 55% of the drug is excreted unchanged in the urine within 24 hours after intraperitoneal injection, 15% as acetamide, and 10% as acetic acid; approximately 7% of the dose is excreted as carbon dioxide through the lungs, and less than 1% is excreted in the feces within 24 hours. In mice, the highest drug concentrations are found in the liver and kidneys, while the lowest concentrations are found in the brain. Metabolisms/Metabolites 35–65% of the oral dose is excreted unchanged in the urine (this provides the therapeutic effect of the drug). …It is metabolized to acetamide.

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Biological Half-Life
The half-life in patients with normal renal function is 5-10 hours.
...It increases with increasing dose; the half-life in patients with normal renal function has been reported to be approximately 3.5-10 hours.

Protein Binding
Currently, there are no known binding interactions. Consuming alcoholic beverages and acetylhydroxamic acid simultaneously results in a non-itchy red maculopapular rash approximately 30 to 45 minutes after ingestion. The rash may be accompanied by systemic fever and tingling, and usually resolves spontaneously within 30 to 60 minutes. Acetylhydroxamic acid chelates iron upon oral administration and may chelate other heavy metals; this may lead to reduced intestinal absorption of both. Parenteral administration is recommended if iron therapy is needed. In vitro studies have shown that acetylhydroxamic acid and methylamine have a synergistic effect in inhibiting pH increases induced by urease-producing Proteus spp. Acetylhydroxamic acid enhances the antibacterial activity of methylamine against these bacteria… Non-human Toxicity Values Mouse intraperitoneal LD50: 2.5 g/kg Mouse oral LD50: 5 g/kg Rat oral LD50: 4.8 g/kg

Acetylhydroxamic acid may cause developmental toxicity depending on state or federal labeling requirements. Acetylhydroxamic acid belongs to the acetylhydroxamic acid class of compounds and has an acetamide structure, where one amino hydrogen atom is replaced by a hydroxyl group. It is an EC 3.5.1.5 (urease) inhibitor and a metabolite of algae. Its function is similar to acetamide; it is a tautomer of N-hydroxyacetylimine. Acetylhydroxamic acid is a drug synthesized from hydroxylamine and ethyl acetate, and its structure is similar to urea. In urine, it acts as an antagonist to the bacterial enzyme urease. Acetylhydroxamic acid does not have direct antibacterial activity and does not directly acidify urine. Acetylhydroxamic acid can be used in combination with antibiotics or medical interventions to treat chronic urea-degrading urinary tract infections. Acetylhydroxamic acid is a urease inhibitor. Its mechanism of action is as a urease inhibitor. Acetylhydroxamic acid has been reported in Arabidopsis thaliana and Chlamydomonas reinhardtii, and relevant data are available. Indications Acetylhydroxamic acid can be used in combination with antibiotics or other medical treatments for the treatment of chronic urea-degrading urinary tract infections. Mechanism of Action Acetylhydroxamic acid reversibly inhibits bacterial urease. This inhibits the hydrolysis of urea and the production of ammonia in the urine of urea-degrading bacteria, leading to a decrease in urine pH and ammonia levels. Antibiotics are more effective in this situation, thus enhancing their efficacy and improving cure rates. Acetylhydroxamic acid inhibits the hydrolysis of urea and the production of ammonia in the urine of urea-degrading bacteria by reversibly inhibiting bacterial urease and nickel, an essential component of urease chelation. This enzyme inhibition reduces urine alkalinity and ammonia concentration, thereby enhancing the efficacy of antibiotics and reducing the formation of urinary tract stones. Therapeutic Uses Enzyme Inhibitor Acetylhydroxamic acid is indicated for the prevention of struvite formation caused by urease-producing bacteria such as Proteus. Its use can enhance the efficacy of urinary tract antimicrobial agents, especially after surgical removal of existing stones. The use of acetylhydroxamic acid can also increase the likelihood of reducing the frequency and rate of new stone formation. /Included in US product label/
Acetylhydroxamic acid is indicated for the treatment of chronic urease-degrading urinary tract infections caused by urease-producing bacteria. It works by inhibiting urease activity, reducing ammonia and alkalinity in the urine due to urease hydrolysis. /Included in US product label/

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Drug Warnings
Acetylhydroxamic acid is not indicated for the dissolution of existing stones, as an alternative to indicated surgical treatment, for urinary tract infections that can be controlled by culture-specific oral antimicrobial agents, or for urinary tract infections caused by non-urease-producing bacteria.
Acetylhydroxamic acid is contraindicated during pregnancy because animal studies have shown that acetylhydroxamic acid at doses of 750 mg/kg body weight and above can cause leg deformities. At doses of 1500 mg/kg, encephalocele and encephalocele have occurred. In addition, beagle puppies given 25 mg/kg acetylhydroxamic acid daily during pregnancy have developed heart, tailbone, and abdominal wall malformations. It is currently unknown whether acetylhydroxamic acid is excreted into breast milk. Although there are no records of adverse reactions in humans, it is not recommended for use by breastfeeding women due to the potential for serious adverse effects on nursing infants. Approximately 30% of patients taking acetylhydroxamic acid have reported headaches within 48 hours of starting treatment; however, some clinicians have reported mild, transient headaches in 70-75% of patients at the beginning of treatment. Headaches are usually mild, respond to oral salicylates, and typically resolve spontaneously. Headaches are not associated with dizziness, tinnitus, or visual or auditory disturbances. Approximately 20-25% of patients taking this medication experience adverse symptoms. For more complete data on acetylhydroxamic acid (12 total), please visit the HSDB records page.

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Pharmacodynamics
Acetylhydroxamic acid is a drug synthesized from hydroxylamine and ethyl acetate, with a structure similar to urea. In urine, it acts as an antagonist of bacterial urease. Acetylhydroxamic acid does not have direct antibacterial activity, nor does it directly acidify urine.

C2H5NO2

75.0666

75.032

546-88-3

1990

Typically exists as solid at room temperature

1.2±0.1 g/cm3

231.4ºC at 760 mmHg

88-90 °C(lit.)

1.421

-1.59

2

2

0

5

42.9

0

O([H])N([H])C(C([H])([H])[H])=O

RRUDCFGSUDOHDG-UHFFFAOYSA-N

InChI=1S/C2H5NO2/c1-2(4)3-5/h5H,1H3,(H,3,4)

N-hydroxyacetamide

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 : ~250 mg/mL (~3330.23 mM)
H2O : ~100 mg/mL (~1332.09 mM)

Solubility in Formulation 1: ≥ 2.08 mg/mL (27.71 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (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 20.8 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: ≥ 2.08 mg/mL (27.71 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (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 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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Solubility in Formulation 3: ≥ 2.08 mg/mL (27.71 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 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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Solubility in Formulation 4: 100 mg/mL (1332.09 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication.

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