Absorption, Distribution and Excretion
Radiolabeled drug studies indicate that furazolidone is well absorbed following oral administration
After a single oral dose of 100 mg/kg body weight to rats, only 3% of the dose was recovered in the feces as unmetabolized compound.

---

Metabolism / Metabolites
Furazolidone is rapidly and extensively metabolized; the primary metabolic pathway identified begins with nitro-reduction to the aminofuran derivative. Two major metabolites are produced: 3-amino-2-oxazolidone (AOZ) or beta-hydroxyethylhydrazine (HEH). AOZ is responsible for monoamine oxidase inhibition. Detoxification and elimination of the drug is done primarily by conjugation with glutathione.
In vitro metabolism of furazolidone by milk xanthine oxidase and rat liver homogenate yielded approximately equal amounts (30%) of 2,3-dihydro-3-cyano-methyl-2-hydroxyl-5-nitro-1a,2-di(2-oxo-oxazolidine-3-yl)imi nomethylfuro(2,3b)furan, and 3-(4-cyano-2-oxobutyl-lideneamino)-2-oxazolidone. The latter was also isolated from the urine of rabbits given on oral dose of furazolidone.
Furazolidone is an antimicrobial compound used in human and veterinary medicine. The aim of this investigation was to determine its genotoxic capacity in vitro and in vivo. We used the human lymphocyte culture system to detect the effect of 2.0, 4.0, 6.0, 8.0, or 10.0 ug/ml, and the mouse bone marrow assay to determine the effect of 8.6, 30.0, or 75.0 mg/kg furazolidone. In both systems we determined the frequency of sister-chromatid exchanges (SCE), the cell proliferation kinetics (CPK), and the mitotic index (MI). The in vitro results showed a significant SCE increase starting from the second dose tested and a CPK and MI decrease starting from the third dose. The in vivo results showed a SCE increase with the two high doses tested, but no significant modification was found in the CPK and MI with the three doses tested in the experiment.
In vitro metabolism of furazolidone (N-(5-nitro-2-furfuryliden)-3-amino-2-oxazolidone) was investigated by using milk xanthine oxidase and rat liver 9000 g supernatant. A new type of reduction product was isolated as 1 of the main metabolites from the incubation mixture and it was tentatively identified as 2,3-dihydro-3-cyanomethyl-2-hydroxyl-5-nitro-1a,2-di(2-oxo-oxazolidin-3-yl)imino methyl-furo(2,3-b)furan. The formation of N-(5-amino-2-furfurylidene)-3-amino-2-oxazolidone as a minor metabolite of nitrofuran in a milk xanthine oxidase system was demonstrated. The aminofuran derivative was easily degraded by milk xanthine oxidase under aerobic, but not anaerobic, conditions. The degradation appears to be due to superoxide anion radicals, hydroxy radicals and/or singlet O2, which are produced in this enzyme system. (Furazolidone, an antibacterial nitrofuran widely used as a veterinary medicine, was mutagenic in Escherichia coli WP2 and Salmonella typhimurium TA100 and tumorigenic in rats).

---

Biological Half-Life
10 minutes

Interactions
Rarely, patients receiving oral furazolidone have exhibited a disulfiram-like reaction to alcohol characterized by flushing, slight temperature elevation, hypotension, dyspnea, and, in some cases, a sense of constriction in the chest.

---

Non-Human Toxicity Values
LD50 Rat oral 2336 mg/kg
LD50 Mouse oral 1782 mg/kg
LD50 Mouse ip 300 mg/kg

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

Furazolidone can cause cancer according to The Environmental Protection Agency (EPA).
Furazolidone is a member of the class of oxazolidines that is 1,3-oxazolidin-2-one in which the hydrogen attached to the nitrogen is replaced by an N-{[(5-nitro-2-furyl)methylene]amino} group. It has antibacterial and antiprotozoal properties, and is used in the treatment of giardiasis and cholera. It has a role as an EC 1.4.3.4 (monoamine oxidase) inhibitor, an antitrichomonal drug, an antiinfective agent and an antibacterial drug. It is a member of oxazolidines and a nitrofuran antibiotic.
A nitrofuran derivative with antiprotozoal and antibacterial activity. Furazolidone binds bacterial DNA which leads to the gradual inhibition of monoamine oxidase. (From Martindale, The Extra Pharmacopoeia, 30th ed, p514)
Furazolidone is a nitrofuran antimicrobial agent used in the treatment of diarrhea or enteritis caused by bacteria or protozoan infections. Furazolidone is also active in treating typhoid fever, cholera and salmonella infections.
A nitrofuran derivative with antiprotozoal and antibacterial activity. Furazolidone acts by gradual inhibition of monoamine oxidase. (From Martindale, The Extra Pharmacopoeia, 30th ed, p514)

---

Drug Indication
For the specific and symptomatic treatment of bacterial or protozoal diarrhea and enteritis caused by susceptible organisms.

---

Mechanism of Action
Furazolidone and its related free radical products are believed to bind DNA and induce cross-links. Bacterial DNA is particularly susceptible to this drug leading to high levels of mutations (transitions and transversions) in the bacterial chromosome.
We are studying the development of unilateral malformations. Several chemicals elicit right sided limb defects both in vivo and in vitro. For example, nitroheterocyclics such as furazolidone (FZ) induce asymmetric defects in rat embryos in vitro. Potential mechanisms include asymmetric drug delivery; intrinsic difference between the cells of the left and right limbs; physiological asymmetry (e.g. in tissue oxygen), secondary to another primary asymmetry (e.g. in limb vasculature). In one series of experiments, we have investigated the role of an asymmetry in drug delivery and/or tissue oxygen. 10.3 days embryonic age rat embryos were explanted and cultured for two hours to allow 'recovery'. Embryos were then exteriorised (removal from yolk sac and amnion, retaining intact circulation) and cultured in the presence of 20 uM FZ with 5% O2 for 24h. The assumption was that exteriorisation would abolish any drug delivery or tissue oxygen asymmetry, by direct embryonic exposure to the medium. As previously described, FZ induced right sided defects (limb, eye and fore-brain) in 42% of intact yolk sac embryos. In contrast, exposure of exteriorised embryos to FZ induced a 34% incidence of abnormalities which were identical, but exclusively left sided. The results do not support a simple hypothesis that asymmetric drug delivery or tissue oxygen levels are responsible for the unilateral defects. We are investigating two potential explanations: a) Exteriorisation specifically reverses limb bud susceptibility, b) A secondary asymmetry e.g. mitochondrial maturity is altered by exteriorisation which then acts to invert the limb response. In a second series of experiments, we have also investigated a possible primary asymmetry in the development of the limb vasculature, using whole mount in situ hybridisation with a probe specific for early endothelial cell precursors (flk-1). The results are being analysed using confocal microscopy to image the limb vascular architecture.

---

Therapeutic Uses
Furazolidone is used in the treatment of cholera when anti-infective therapy is indicated as an adjunct to fluid and electrolyte replacement.
Furazolidone is used for the specific and symptomatic treatment of diarrhea and enteritis caused by susceptible bacteria or protozoa.
Furazolidone ... often is prescribed /to treat giardiasis in/ children because the drug is available in a pleasant liquid formulation. ... Furazolidone is the only drug currently approved by the US FDA for treatment of giardiasis.

---

Drug Warnings
After use of furazolidone as a drug, acute nausea, emesis, occasional diarrhea, abdominal pain and intestinal bleeding were observed; hepatic damage, as evidenced by biochemical tests, and peripheral neuropathy were also seen.
Nausea and vomiting are the most common side effects of oral furazolidone therapy; abdominal pain and diarrhea occasionally occur. These effects can be minimized or eliminated by reducing dosage or discontinuing the drug.
Hypersensitivity reactions to oral furazolidone have occurred in a small number of patients and generally subside with discontinuance of the drug. Hypersensitivity reactions include a fall in blood pressure, angioedema, fever, arthralgia, urticaria, and a vesicular or morbilliform rash. Erythema multiforme, pulmonary infiltration, and pulmonary eosinophilia also have been reported and may be due to hypersensitivity.
Headache and malaise occur occasionally with oral furazolidone therapy and can be minimized or eliminated by reducing dosage or discontinuing the drug. Following oral furazolidone administration, hypoglycemia, agranulocytosis, and, in one patient, partial deafness and dizziness have also been reported. Rarely, some patients receiving oral furazolidone experience a disulfiram-like reaction to alcohol. Polyneuritis and hemolytic anemia (in patients with glucose-6-phosphate dehydrogenase deficiency and in neonates) also have been reported rarely.
For more Drug Warnings (Complete) data for FURAZOLIDONE (6 total), please visit the HSDB record page.

---

Pharmacodynamics
Furoxone has a broad antibacterial spectrum covering the majority of gastrointestinal tract pathogens including E. coli, staphylococci, Salmonella, Shigella, Proteus, Aerobacter aerogenes, Vibrio cholerae and Giardia lamblia. Its bactericidal activity is based upon its interference with DNA replication and protein production; this antimicrobial action minimizes the development of resistant organisms.

C8H7N3O5

225.16

225.038

67-45-8

Furazolidone-d4;1217222-76-8

5323714

Light yellow to yellow solid powder

1.7±0.1 g/cm3

353.4±52.0 °C at 760 mmHg

254-256ºC (dec.)

167.5±30.7 °C

0.0±0.8 mmHg at 25°C

1.670

-0.49

0

6

2

16

326

0

C1COC(=O)N1/N=C/C2=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)

DMSO : ~5.56 mg/mL (~24.69 mM)
H2O : ~0.67 mg/mL (~2.98 mM)

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.

---

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).

View More

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)

---

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).

View More

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

---

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.

---

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