Drug compounds have included stable heavy isotopes of carbon, hydrogen, and other elements, mostly as quantitative tracers while the drugs were being developed. Because deuteration may have an effect on a drug's pharmacokinetics and metabolic properties, it is a cause for concern [1].

Absorption, Distribution and Excretion
Radiolabeled drug studies have shown that furazolidone is well absorbed after oral administration. In rats, only 3% of a single oral dose of 100 mg/kg body weight of furazolidone was excreted in feces as unmetabolized compounds. Metabolism/Metabolites Furazolidone is rapidly and extensively metabolized; the established major metabolic pathway begins with nitro reduction to aminofuran derivatives. There are two main metabolites: 3-amino-2-oxazolidinone (AOZ) or β-hydroxyethylhydrazine (HEH). AOZ inhibits monoamine oxidase. Detoxification and clearance of this drug are primarily accomplished through binding to glutathione. In vitro experiments showed that furazolidone, after being metabolized by milk xanthine oxidase and mouse liver homogenate, produced approximately equal amounts (30%) of 2,3-dihydro-3-cyanomethyl-2-hydroxy-5-nitro-1a,2-di(2-oxooxazolidin-3-yl)iminomethylfuran[2,3b]furan and 3-(4-cyano-2-oxobutylimino)-2-oxazolidinone. The latter was also isolated from the urine of rabbits orally administered furazolidone. Furazolidone is an antimicrobial compound used in human and veterinary medicine. This study aimed to determine its in vitro and in vivo genotoxicity. We used a human lymphocyte culture system to detect the effects of furazolidone at concentrations of 2.0, 4.0, 6.0, 8.0, or 10.0 μg/ml, and mouse bone marrow assays to determine the effects of furazolidone at concentrations of 8.6, 30.0, or 75.0 mg/kg. In both systems, we measured the frequency of sister chromatid exchange (SCE), cell proliferation kinetics (CPK), and mitotic index (MI). In vitro results showed that SCE significantly increased from the second dose onwards, while CPK and MI significantly decreased from the third dose onwards. In vivo results showed that both high doses tested led to an increase in SCE, but no significant changes in CPK and MI were observed at any of the three doses tested. The in vitro metabolism of furazolidone (N-(5-nitro-2-furanomethylene)-3-amino-2-oxazolidinone) was studied using milk xanthine oxidase and 9000 g rat liver supernatant. A novel reducing product was isolated from the incubation mixture as one of the major metabolites and preliminarily identified as 2,3-dihydro-3-cyanomethyl-2-hydroxy-5-nitro-1a,2-bis(2-oxazolidin-3-yl)iminomethyl-furano[2,3-b]furan. Studies have shown that a small amount of nitrofuran metabolites in the lactoxine oxidase system is N-(5-amino-2-furanmethylene)-3-amino-2-oxazolidinone. This aminofuran derivative is readily degraded by lactoxine oxidase under aerobic conditions but is not easily degraded under anaerobic conditions. The degradation process appears to be related to superoxide anion radicals, hydroxyl radicals, and/or singlet oxygen generated by the enzyme system. (Furazolidinone is a widely used veterinary antimicrobial nitrofuran drug, mutagenic to Escherichia coli WP2 and Salmonella typhimurium TA100, and tumorigenic in rats.)

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Biological half-life
10 minutes

Interactions
In rare cases, patients taking furazolidone orally may experience a disulfiram-like alcohol reaction, characterized by facial flushing, mild fever, hypotension, dyspnea, and in some cases, chest tightness. Non-human Toxicity Values Oral LD50 in rats: 2336 mg/kg Oral LD50 in mice: 1782 mg/kg Intraperitoneal LD50 in mice: 300 mg/kg

[1]. Impact of Deuterium Substitution on the Pharmacokinetics of Pharmaceuticals. Ann Pharmacother. 2019;53(2):211-216.

[2]. A novel application of furazolidone: anti-leukemic activity in acute myeloid leukemia. PLoS One. 2013 Aug 9;8(8):e72335.

According to the U.S. Environmental Protection Agency (EPA), furazolidone may be carcinogenic. Furazolidone belongs to the oxazolidinyl class of compounds, with the chemical formula 1,3-oxazolidin-2-one, in which the hydrogen atom bonded to the nitrogen atom is replaced by N-{[(5-nitro-2-furanyl)methylene]amino}. It has antibacterial and antiprotozoal properties and is used to treat giardiasis and cholera. It is an EC 1.4.3.4 (monoamine oxidase) inhibitor, and also an antitrichomonal, anti-infective, and antibacterial drug. It belongs to the oxazolidinyl class of compounds and is also a nitrofuran antibiotic. Furazolidone is a nitrofuran derivative with antiprotozoal and antibacterial activity. It binds to bacterial DNA, thereby gradually inhibiting the activity of monoamine oxidase. (Excerpt from Martindale Pharmacopoeia, 30th edition, page 514) Furazolidone is a nitrofuran antibacterial drug used to treat diarrhea or enteritis caused by bacterial or protozoal infections. Furazolidone can also be used to treat typhoid fever, cholera, and Salmonella infections. Furazolidone is a nitrofuran derivative with antiprotozoal and antibacterial activity. Its mechanism of action is through the gradual inhibition of monoamine oxidase. (Excerpt from Martindale Pharmacopoeia, 30th edition, p. 514) Indications: For the specific and symptomatic treatment of bacterial or protozoal diarrhea and enteritis caused by susceptible microorganisms. Mechanism of Action: Furazolidone and its associated free radical products are believed to bind to DNA and induce DNA cross-linking. Bacterial DNA is particularly sensitive to this drug, leading to high levels of mutations (transversions and subversions) in bacterial chromosomes. We are investigating the development of unilateral malformations. Many chemicals can induce right-sided limb defects both in vivo and in vitro. For example, nitroheterocyclic compounds such as furazolidone (FZ) can induce asymmetric defects in rat embryos in vitro. Potential mechanisms include asymmetric drug delivery; intrinsic differences in cells between the left and right limbs; and physiological asymmetries (e.g., tissue oxygenation) secondary to other primary asymmetries (e.g., limb vascular system). In a series of experiments, we investigated the role of asymmetric drug delivery and/or tissue oxygenation. 10.3-day-old rat embryos were retrieved and cultured for two hours to allow them to “recover.” The embryos were then retrieved (yolk sac and amnion removed, preserving the intact circulatory system) and cultured for 24 hours in a medium containing 20 μM FZ and 5% O2. We hypothesized that upon embryo retrieval, drug delivery or tissue oxygenation asymmetries would be eliminated due to direct exposure to the medium. As previously stated, FZ induced right-sided defects (limbs, eyes, and forebrain) in 42% of embryos with intact yolk sacs. In contrast, in 34% of embryos exposed to FZ after retrieval, the same abnormalities were observed, but all were located on the left side. These results do not support the simplistic assumption that asymmetric drug delivery or tissue oxygenation is the cause of unilateral defects. We are investigating two possible explanations: a) embryo removal specifically reverses limb bud susceptibility; b) embryo removal alters secondary asymmetries, such as mitochondrial maturity, thereby reversing limb responses. In a second set of experiments, we also used whole-tissue in situ hybridization with probes targeting early endothelial cell precursors (flk-1) to investigate potential primary asymmetries in limb vascular development. Confocal microscopy is currently being used for imaging analysis of limb vascular structures.

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Therapeutic Uses
Furazolone is used to treat cholera and can be used as an adjunct to anti-infective therapy in conjunction with fluid and electrolyte supplementation.
Furazolone is used to treat diarrhea and enteritis caused by susceptible bacteria or protozoa, including both specific and symptomatic treatment.
Furazolone…is commonly used to treat giardiasis in children because it is available in a palatable liquid formulation.
Furazolone is currently the only drug approved by the US FDA for the treatment of giardiasis.
Drug Warnings
Acute nausea, vomiting, occasional diarrhea, abdominal pain, and intestinal bleeding have been observed after taking furazolidone; biochemical tests have confirmed liver damage and peripheral neuropathy.
Nausea and vomiting are the most common side effects of oral furazolidone treatment; abdominal pain and diarrhea occur occasionally. Reducing the dose or discontinuing the drug can alleviate or eliminate these side effects.
Hypersensitivity reactions to oral furazolidone have been reported in a few patients, which usually subside upon discontinuation of the drug. Hypersensitivity reactions include decreased blood pressure, angioedema, fever, arthralgia, urticaria, and vesicular or measles-like rashes.
Erythema multiforme, pulmonary infiltration, and pulmonary eosinophilia have been reported after taking furazolidone; these symptoms may be related to allergic reactions.
Headache and malaise are occasionally reported after taking oral furazolidone treatment, which can be alleviated or eliminated by reducing the dose or discontinuing the drug. Hypoglycemia, agranulocytosis, and one patient experienced partial hearing loss and vertigo after taking oral furazolidone have also been reported. In rare cases, some patients taking oral furazolidone may experience a disulfiram-like reaction to alcohol. Polyneuritis and hemolytic anemia (seen in patients with glucose-6-phosphate dehydrogenase deficiency and newborns) have also been rarely reported. For more complete data on furazolidone (6 of 6), please visit the HSDB record page. Pharmacodynamics: Furazolidone has broad-spectrum antibacterial activity, covering most gastrointestinal pathogens, including Escherichia coli, Staphylococcus, Salmonella, Shigella, Proteus, Enterobacter aerogenes, Vibrio cholerae, and Giardia lamblia. Its bactericidal activity is based on interference with DNA replication and protein synthesis; this antibacterial action minimizes the development of resistant bacteria.

C8H7N3O5

225.15828

229.064

1217222-76-8

Furazolidone;67-45-8

5323714

Yellow crystals from DMF (N,N-dimethylformamide)

254-256
255 °C
MP: 254-256 °C (decomposes)
MP: 275 °C (decomp)
255 °C

1.435

0

6

2

16

326

0

C1COC(=O)N1N=CC2=CC=C(O2)[N+](=O)[O-]

PLHJDBGFXBMTGZ-WEVVVXLNSA-N

InChI=1S/C8H7N3O5/c12-8-10(3-4-15-8)9-5-6-1-2-7(16-6)11(13)14/h1-2,5H,3-4H2/b9-5+

3-[(E)-(5-nitrofuran-2-yl)methylideneamino]-1,3-oxazolidin-2-one

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)

May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.

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Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)
*Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution.
Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)
Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil)
Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals).

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Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)]
*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.
Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline)
Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline)
Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline
Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil)
Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)

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Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium)
Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose
Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals).

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Oral Formulation 3: Dissolved in PEG400
Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose
Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose
Oral Formulation 6: Mixing with food powders

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Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.

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