Absorption, Distribution and Excretion
Well absorbed from the GI tract following oral administration.
Well absorbed from gastrointestinal tract.
Well distributed throughout body fluids.
Elimination: Renal- Unchanged, 36 to 65%; as acetamide, 9 to 14%. Respiratory - As carbon dioxide, 20 to 40%.
In rodents, about 55% of an intraperitoneal dose is excreted in urine as unchanged drug, 15% as acetamide, and 10% as acetate within 24 hours; approximately 7% of the dose is excreted by the lungs as carbon dioxide and less than 1% is excreted in feces within 24 hours.
In mice, highest concentrations of the drug occur in the liver and kidney, while the lowest concentrations occur in the brain.

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Metabolism / Metabolites
35-65% of oral dose excreted unchanged in urine (which provides the drug's therapeutic effect).
...is metabolized to acetamide.

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Biological Half-Life
5-10 hours in patients with normal renal function
...increases with increasing dose and reportedly ranges from about 3.5-10 hours in patients with normal renal function.

Protein Binding
No known binding

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Interactions
Concurrent use of alcoholic beverages with acetohydroxamic acid has resulted in a nonpruritic, reddish, macular skin rash about 30 to 45 minutes after ingestion. The rash may be associated with a general feeling of warmth and tingling, and usually disappears spontaneously in 30 to 60 minutes.
Acetohydroxamic acid chelates iron and possibly other heavy metals with concurrent oral administration; this may result in reduced intestinal absorption of both; if iron therapy is indicated, parenteral administration of iron is recommended.
In vitro studies indicate that acetohydroxamic acid and methenamine have a synergistic effect in inhibiting increases in pH caused by urease-producing Proteus spp. and that acetohydroxamic acid potentiates the antibacterial effect of methenamine against these bacteria...

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Non-Human Toxicity Values
LD50 Mouse ip 2.5 g/kg
LD50 Mouse oral 5 g/kg
LD50 Rat oral 4.8 g/kg

Acetohydroxamic Acid can cause developmental toxicity according to state or federal government labeling requirements.
Acetohydroxamic acid is a member of the class of acetohydroxamic acids that is acetamide in which one of the amino hydrogens has been replaced by a hydroxy group. It has a role as an EC 3.5.1.5 (urease) inhibitor and an algal metabolite. It is functionally related to an acetamide. It is a tautomer of a N-hydroxyacetimidic acid.
Acetohydroxamic Acid, a synthetic drug derived from hydroxylamine and ethyl acetate, is similar in structure to urea. In the urine, it acts as an antagonist of the bacterial enzyme urease. Acetohydroxamic Acid has no direct antimicrobial action and does not acidify urine directly. It is used, in addition to antibiotics or medical procedures, to treat chronic urea-splitting urinary infections.
Acetohydroxamic acid is an Urease Inhibitor. The mechanism of action of acetohydroxamic acid is as an Urease Inhibitor.
Acetohydroxamic acid has been reported in Arabidopsis thaliana and Chlamydomonas reinhardtii with data available.

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Drug Indication
Used, in addition to antibiotics or medical procedures, to treat chronic urea-splitting urinary infections.

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Mechanism of Action
Acetohydroxamic Acid reversibly inhibits the bacterial enzyme urease. This inhibits the hydrolysis of urea and production of ammonia in urine infected with urea-splitting organisms, leading to a decrease in pH and ammonia levels. As antimicrobial agents are more effective in such conditions, the effectiveness of these agents is amplified, resulting in a higher cure rate.
Inhibits the hydrolysis of urea and production of ammonia in urine infected with urea-splitting bacteria, by reversible inhibition of the bacterial enzyme urease, and by the chelation of nickel, an essential component of urease enzymes. Such enzyme inhibition results in reduction of both urine alkalinity and ammonia concentration. The effectiveness of antibacterial medication is then enhanced and the formation of urinary calculi reduced.

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Therapeutic Uses
Enzyme Inhibitors
Acetohydroxamic acid is indicated in the prophylaxis of struvite calculi formation that is promoted by urease-producing bacteria such as Proteus. Its use may enhance effectiveness of urinary antibacterials, especially following surgical removal of existing stones. Use of acetohydroxamic acid also improves the possibility of reducing the frequency and rate of new stone formation. /Included in US product labeling/
Acetohydroxamic acid is indicated as an adjunct in the treatment of chronic, urea-splitting urinary tract infections caused by urease-producing bacteria. Its inhibition of urease activity decreases the urinary ammonia and alkalinity produced from the enzyme hydrolysis of urea. /Included in US product labeling/

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Drug Warnings
Acetohydroxamic acid is not indicated for dissolution of existing calculi, replacement of indicated surgical treatment, urinary tract infections controllable by culture-specific oral antibacterials, or urinary tract infections caused by nonurease producing organisms.
Use of acetohydroxamic acid is contraindicated during pregnancy since studies in animals have shown it to cause leg deformities at doses of 750 mg/kg of body weight and above. At doses of 1500 mg/kg, exencephaly and encephalocele occurred. Also, cardiac, coccygeal, and abdominal-wall anomalies developed in pups of beagle dogs given 25 mg/kg a day during pregnancy.
It is not known if acetohydroxamic acid is distributed into breast milk. Although problems in humans have not been documented, its use is not recommended in breast-feeding mothers because of the potential for serious adverse effects in the nursing infant.
Headache, appearing during the first 48 hours of treatment, reportedly occurs in approximately 30% of patients receiving acetohydroxamic acid; however, several clinicians reported that mild, transient headache occurred in 70-75% of patients during initiation of therapy. Headache is generally mild, responsive to oral salicylate analgesics, and usually disappears spontaneously. Headache has not been associated with vertigo, tinnitus, or visual or auditory disturbances. Malaise occurs in about 20-25% of patients receiving the drug.
For more Drug Warnings (Complete) data for ACETOHYDROXAMIC ACID (12 total), please visit the HSDB record page.

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Pharmacodynamics
Acetohydroxamic Acid, a synthetic drug derived from hydroxylamine and ethyl acetate, is similar in structure to urea. In the urine, it acts as an antagonist of the bacterial enzyme urease. Acetohydroxamic Acid has no direct antimicrobial action and does not acidify urine directly.

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.)