Absorption, Distribution and Excretion
Absorption was good. Approximately 1% of the (14)C was recovered from urine, feces, and bile in the form of unchanged 5-nitro-2-furanaldehyde hemicarbamate, indicating significant metabolism of the substance in rats after oral administration of a 100 mg/kg dose. Rats administered 100 mg/kg of 5-nitro-2-furanaldehyde hemicarbamate-[formyl-14C]…excreted approximately 66%, 35%, and 1% of the activity in the form of CO2 in urine, feces, and respiratory gases, respectively, within 96 hours, with most of the (14)C activity eliminated within 48 hours. After 48 hours, the recovery rate of (14)C in bile was approximately 27%.
In rats administered a dose of 100 mg/kg, plasma concentrations reached 4.5 mg/L after 4 hours, with 34% bound to proteins. In rats administered a dose of 200 mg/kg, approximately 4.6% was excreted in urine and 0.5% in feces within 48 hours. Following oral administration of 5-nitro-2-furanaldehyde bis(carbamate), the substance was detected in canine cerebrospinal fluid within 2 hours.
Metabolism/Metabolites
Nitrofuran compounds, including nitrofurans, undergo metabolic reduction at the nitro group to produce active substances that can covalently bind to cellular macromolecules (Polnaszek et al., 1984; Kutcher and McCalla, 1984; McCalla, 1979; McCalla et al., 1975).
/Nitrofuranaldehyde has been shown to be reduced by enzymes and reductases in mammalian livers. The isolation of hydroxylamine intermediates is not uncommon in in vitro studies. This study investigated the in vivo distribution of the antibiotic nitrofurazone in isolated rat livers after a single perfusion. The effects of steady-state drug concentration and perfusion fluid composition were assessed. In perfusion fluids lacking glutathione precursors (glycine, glutamic acid, and cysteine), higher concentrations (120 μg/ml) of nitrofurazone resulted in a significant increase in bile flow (from 1.01 ± 0.07 μl/min/g to 2.33 ± 1.07 μl/min/g), substantial efflux of disulfide-containing glutathione in bile (from 0.55 ± 0.07 nmol/min/g to 60.6 ± 25.4 nmol/min/g), and a sharp decrease in vena cava glutathione efflux (to undetectable levels) and tissue glutathione levels (from 5.74 ± 0.20 μmol/g to 2.68 ± 0.13 μmol/g). These parameters did not recover to control levels even after drug withdrawal. Low concentrations (30 μg/ml) of furanone, with or without amino acid supplementation, and high concentrations (with amino acid supplementation) of furanone resulted in weak toxicity. A novel conjugated metabolite of furanone and glutathione was detected using (35)S methionine. Data suggest that adequate glutathione levels can mitigate the toxicity of reactive oxygen species (ROS) generated by the nitro redox cycle and reactive metabolites from further reduction of furanone, but insufficient glutathione to clear these ROS may damage the liver. Nitrofurans, including furanone, undergo metabolic reduction at the nitro group, generating ROS that can covalently bind to cellular macromolecules. Half-life: 5 hours.

Toxicity Summary
The exact mechanism of action is unclear. Furazolidone inhibits a variety of bacterial enzymes, particularly those involved in the aerobic and anaerobic degradation of glucose and pyruvate. This activity is believed to also affect pyruvate dehydrogenase, citrate synthase, malate dehydrogenase, glutathione reductase, and pyruvate decarboxylase. Toxicity Data
Rat LD50 = 590 mg/kg

[1]. Activation of nitrofurazone by azoreductases: multiple activities in one enzyme. Sci Rep. 2011;1:63.

[2]. Mode of action of nitrofurazone. J Bacteriol. 1970 Dec;104(3):1126-34.

[3]. Effect of nitrofurazone on bacterial RNA and ribosome synthesis and on the function of ribosomes. Chem Biol Interact. 1976 Jul;14(1-2):81-91.

[4]. Toxicity and carcinogenicity of nitrofurazone in F344/N rats and B6C3F1 mice. Food Chem Toxicol. 1989 Feb;27(2):129-37.

[5]. The activity of nitrofurazone and furazolidone against Leishmania donovani, L. major and L. enriettii in vitro and in vivo. Ann Trop Med Parasitol. 1988 Oct;82(5):453-6.

According to the U.S. Environmental Protection Agency (EPA), nitrofurazone may be carcinogenic. Nitrofurazone is an odorless, pale yellow needle-like or yellow powder. Its saturated aqueous solution has a pH of 6.0-6.5. Alkaline solutions are deep orange. (NTP, 1992) Nitrofurazone is a hemi-aminourea drug, formed by the condensation of hemi-aminourea and 5-nitrofuranaldehyde. It is a broad-spectrum antibacterial drug, although its activity against Pseudomonas spp. is weak, but it can still be used topically to treat burns, ulcers, wounds, and skin infections. It is an antibacterial drug belonging to the hemi-aminourea and nitrofuran antibiotics. Furanaldehyde or nitrofurazone is a topical anti-infective agent effective against both Gram-negative and Gram-positive bacteria. It is used to treat superficial wounds, burns, ulcers, and skin infections. Nifurapone was also previously used orally to treat trypanosomiasis. Except for topical use in dermatology, the FDA has revoked approval for drugs containing nifurapone.
A topical anti-infective agent effective against both Gram-negative and Gram-positive bacteria. Used to treat superficial wounds, burns, ulcers, and skin infections. Nifurapone has also been used orally to treat trypanosomiasis.
A topical anti-infective agent effective against both Gram-negative and Gram-positive bacteria. Used to treat superficial wounds and injuries, as well as skin infections. Nifurapone has also been used orally to treat trypanosomiasis.
See also: Tetracaine sulfate; Nitrofurazone (ingredient)...See more...

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Drug Indications
Used to treat bacterial skin infections caused by susceptible bacteria, including pyoderma, infectious dermatitis, and infections of cuts, wounds, burns, and ulcers.

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Mechanism of Action
The exact mechanism of action is not yet known. Nitrofurazone inhibits a variety of bacterial enzymes, particularly those involved in the aerobic and anaerobic degradation of glucose and pyruvate. It is believed that this activity also affects pyruvate dehydrogenase, citrate synthase, malate dehydrogenase, glutathione reductase, and pyruvate decarboxylase. The antibacterial mechanism of the furan derivative is unclear, but it is speculated that the compound interferes with the enzymatic processes necessary for bacterial growth. The exact mechanism of action of nifuran derivative nifuran is unclear. However, the drug appears to work by inhibiting bacterial enzymes involved in carbohydrate metabolism. Organic matter (e.g., blood, pus, serum) and aminobenzoic acid (p-aminobenzoic acid) inhibit the antibacterial activity of nifuran.

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Therapeutic Uses
Topical anti-infective; urinary tract anti-infective; trypanosome killer
/Nifuran/ has bactericidal activity against a variety of Gram-positive and Gram-negative bacteria present in surface infections… It has been used topically to treat skin and mucous membrane infections.
Nifuran/ can be used to treat…/late-stage trypanosomiasis/ with a certain success rate. Single course of treatment… every 6 hours for 1 week. Three courses of treatment can be administered, with a one-week rest period between each course. It is particularly suitable for treating second- and third-degree burns and post-skin grafting complications with bacterial infections that are unresponsive to common medications but sensitive to nitrofurantoin. …Nitrofurantoin is used to treat susceptible infections of the eyes, ears, nose, urethra, and vagina. …It retains its antibacterial activity in blood, serum, and pus; phagocytosis is not inhibited, and nitrofurantoin does not interfere with wound healing. For more complete data on the therapeutic uses of nitrofurantoin (14 in total), please visit the HSDB record page.

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Drug Warnings
…/Treatment of late-stage trypanosomiasis/Not suitable for patients with fever or debilitated conditions. …It can cause hemolytic anemia in patients with glucose-6-phosphate dehydrogenase deficiency.
When applied topically to the ear…/nitrofurantoin/may cause an allergic skin reaction. …Such reactions…are often similar to the disease being treated.
…This drug reaction can usually be identified by the spread of inflammation to the earlobe and the infection being unresponsive to treatment.
...Pseudomonas and Proteus strains are often resistant.
It has not been proven effective in treating minor burns, wounds, or infected skin ulcers. It may not be effective in treating pyoderma. ...Approximately 0.5-2% of patients will experience an allergic reaction to the drug, sometimes as early as 5 days after starting treatment. ...All formulations of nitrofurazone should be kept away from direct sunlight, excessive heat, and alkaline substances.
For more complete data on nitrofurazone (8 in total), please visit the HSDB record page.

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Pharmacodynamics
Nitrofurazone is a topical antimicrobial agent indicated as adjunctive treatment for second- and third-degree burns that are resistant or potentially resistant to other drugs. Nitrofurazone is also indicated for skin grafts when bacterial contamination may lead to graft rejection or donor site infection, especially in hospitals with a history of resistant bacterial infections.

C6H6N4O4

198.1362

198.038

59-87-0

Nitrofurazone-13C,15N2;1217220-85-3

5447130

Light yellow to yellow solid powder

1.7±0.1 g/cm3

236-240ºC

242-244 °C(lit.)

2 °C

1.674

-0.36

2

5

2

14

261

0

C1=C(OC(=C1)[N+](=O)[O-])/C=N/NC(=O)N

IAIWVQXQOWNYOU-FPYGCLRLSA-N

InChI=1S/C6H6N4O4/c7-6(11)9-8-3-4-1-2-5(14-4)10(12)13/h1-3H,(H3,7,9,11)/b8-3+

[(E)-(5-nitrofuran-2-yl)methylideneamino]urea

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 : ≥ 155 mg/mL (~782.28 mM)

Solubility in Formulation 1: ≥ 2.58 mg/mL (13.02 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 25.8 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: ≥ 2.58 mg/mL (13.02 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 25.8 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.)