Absorption, Distribution and Excretion
Well absorbed.
ABOUT 1% OF (14)C WAS RECOVERED FROM URINE, FECES & BILE AS UNCHANGED 5-NITRO-2-FURALDEHYDE SEMICARBAZONE, SUGGESTING SUBSTANTIAL METABOLISM OF THIS SUBSTANCE IN RAT /AFTER ORAL DOSAGE OF 100 MG/KG/.
RATS DOSED WITH 100 MG/KG 5-NITRO-2-FURALDEHYDE SEMICARBAZONE- [FORMYL-(14)C] ... EXCRETED ABOUT 66%, 35% & 1% OF ACTIVITY IN URINE, FECES & IN RESPIRED AIR AS CO2, RESPECTIVELY, WITHIN 96 HR, & MAJORITY OF (14)C ACTIVITY WAS ELIMINATED WITHIN 48 HR. RECOVERY OF (14)C IN BILE WAS ABOUT 27% AFTER 48 HR.
IN RATS DOSED WITH 100 MG/KG, PLASMA LEVELS OF 4.5 MG/L ... WERE FOUND AFTER 4 HR, 34% OF WHICH WAS BOUND TO PROTEINS. RATS DOSED WITH 200 MG/KG ... EXCRETED ABOUT 4.6% IN URINE & 0.5% IN FECES WITHIN 48 HR. ORALLY ADMIN 5-NITRO-2-FURALDEHYDE SEMICARBAZONE WAS DETECTED IN CEREBROSPINAL FLUID OF DOGS WITHIN 2 HR.

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Metabolism / Metabolites
Nitrofurans, including nitrofural, undergo metabolic reduction at the nitro group to generate reactive species which can covalently bind to cellular macromolecules (Polnaszek et al., 1984; Kutcher & McCalla, 1984; McCalla 1979; McCalla et al., 1975).
/NITROFURAZONE HAS/ BEEN SHOWN TO BE REDUCED BY ENZYMES & PREPN FROM MAMMALIAN LIVER. ... ISOLATION OF A HYDROXYLAMINE INTERMEDIATE IS NOT UNCOMMON IN IN VITRO STUDIES.
The disposition of the antibiotic nitrofurazone was studied in the singlepass isolated perfused rat liver. Both the effects of the steady state level of drug and the composition of the perfusate were evaluated. The higher level (120 ug/ml) of nitrofurazone in a perfusion medium lacking the glutathione precursors, glycine, glutamic acid and cysteine, caused a marked increase in bile flow (from 1.01 + or - 0.07 to 2.33 + or - 1.07 ul/min/g), massiv biliary efflux of glutathione disulfide (from 0.55 + or - 0.07 to 60.6 + or - 25.4 nmol/min/g) and a sharp decline in the caval efflux of glutathione (to undetectable levels) and the tissue level of glutathione (from 5.74 + or - 0.20 to 2.68 + or - 0.13 umol/g). Even after the drug was discontinued, these parameters were not restored to control levels. The lower level (30 ug/ml) of nitrofurazone with or without amino acid supplementatio and the higher level with supplementation induced less dramatic effects. Using (35)S methionine, a new conjugated metabolite of nitrofurazone and glutathione was detected. The data suggest that the toxicity of the reactive oxygen species generated by the redox cycling of the nitro group and the reactive metabolites generated by further reduction of nitrofurazone can be mitigated by adequate glutathione levels, but that livers lacking sufficient glutathione to scavenge these reactive species may be damaged.
Nitrofurans, including nitrofural, undergo metabolic reduction at the nitro group to generate reactive species which can covalently bind to cellular macromolecules.
Half Life: 5 hours

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Biological Half-Life
5 hours

Toxicity Summary
The exact mechanism of action is unknown. Nitrofurazone inhibits several bacterial enzymes, especially those involved in the aerobic and anaerobic degradation of glucose and pyruvate. This activity is believed also to affect pyruvate dehydrogenase, citrate synthetase, malate dehydrogenase, glutathione reductase, and pyruvate decarboxylase.

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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.

Nitrofurazone can cause cancer according to The Environmental Protection Agency (EPA).
Nitrofurazone appears as odorless pale yellow needles or yellow powder. pH (saturated aqueous solution) 6.0 - 6.5. Alkaline solutions are dark orange. (NTP, 1992)
Nitrofurazone is a semicarbazone resulting from the formal condensation of semicarbazide with 5-nitrofuraldehyde. A broad spectrum antibacterial drug, although with little activity against Pseudomonas species, it is used as a local application for burns, ulcers, wounds and skin infections. It has a role as an antibacterial drug. It is a semicarbazone and a nitrofuran antibiotic.
Nitrofural or nitrofurazone is a topical anti-infective agent effective against gram-negative and gram-positive bacteria. It is used for superficial wounds, burns, ulcers, and skin infections. Nitrofural has also been administered orally in the treatment of trypanosomiasis. Except for topical drug products formulated for dermatologic application, the FDA withdrew its approval for the use of drug products containing nitrofurazone.
A topical anti-infective agent effective against gram-negative and gram-positive bacteria. It is used for superficial wounds, burns, ulcers, and skin infections. Nitrofurazone has also been administered orally in the treatment of trypanosomiasis.
A topical anti-infective agent effective against gram-negative and gram-positive bacteria. It is used for superficial WOUNDS AND INJURIES and skin infections. Nitrofurazone has also been administered orally in the treatment of TRYPANOSOMIASIS.
See also: Butacaine Sulfate; Nitrofurazone (component of) ... View More ...

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Drug Indication
For the treatment of bacterial skin infections including pyodermas, infected dermatoses and infections of cuts, wounds, burns and ulcers due to susceptible organisms.

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Mechanism of Action
The exact mechanism of action is unknown. Nitrofurazone inhibits several bacterial enzymes, especially those involved in the aerobic and anaerobic degradation of glucose and pyruvate. This activity is believed also to affect pyruvate dehydrogenase, citrate synthetase, malate dehydrogenase, glutathione reductase, and pyruvate decarboxylase.
MECHANISM OF ANTIBACTERIAL ACTION OF FURAN DERIV IS UNKNOWN, BUT IT IS PRESUMED THAT THE COMPD INTERFERES WITH ENZYMATIC PROCESSES ESSENTIAL TO BACTERIAL GROWTH. /FURAN DERIV/
The exact mechanism of action of nitrofurazone is not known. It appears, howeverthat the drug acts by inhibiting bacterial enzymes involved in carbohydrage metabolism. Oragnic matter (eg, blood pus, serum) and aminobenzoic acid (p-aminobenzoic acid) inhibit the antibacterial action of nitrofurazone.

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Therapeutic Uses
Anti-Infective Agents, Local; Anti-Infective Agents, Urinary; Trypanocidal Agents
/NITROFURAZONE/ IS BACTERICIDAL FOR MANY GRAM POSITIVE & GRAM NEGATIVE ORGANISMS PRESENT IN SURFACE INFECTIONS ... IT HAS BEEN USED TOPICALLY TO TREAT INFECTIONS OF SKIN & MUCOUS MEMBRANES.
NITROFURAZONE MAY BE TRIED IN ... /LATE-STAGE TRYPANOSOMIASIS/ WITH SOME CHANCE OF SUCCESS. SINGLE COURSE OF TREATMENT ... AT 6 HR INTERVALS FOR 1 WK. 3 COURSES MAY BE GIVEN WITH A WEEK'S REST BETWEEN EACH.
IT FINDS USE, ESP, IN TREATMENT OF 2ND & 3RD DEGREE BURNS & IN SKIN GRAFTING IN WHICH THERE ARE COMPLICATIONS FROM BACTERIAL INFECTIONS THAT ARE REFRACTORY TO USUAL DRUGS OF CHOICE BUT IN WHICH SENSITIVITY TO NITROFURAZONE IS DEMONSTRABLE. ... NITROFURAZONE IS USED IN MGMNT OF SUSCEPTIBLE INFECTIONS OF EYE, EAR, NOSE, URETHRA & VAGINA. ... /IT/ RETAINS ITS ANTIBACTERIAL ACTIVITY IN BLOOD, SERUM & PUS; PHAGOCYTOSIS IS NOT INHIBITED & NITROFURAZONE DOES NOT INTERFERE WITH HEALING.
For more Therapeutic Uses (Complete) data for NITROFURAZONE (14 total), please visit the HSDB record page.

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Drug Warnings
... /TREATMENT AS IN LATE-STAGE TRYPANOSOMIASIS/ IS UNSUITABLE FOR FEBRILE OR DEBILITATED PATIENTS. ... IT PRODUCES HEMOLYTIC ANEMIA IN PATIENTS WITH GLUCOSE-6-PHOSPHATE DEHYDROGENASE DEFICIENCY.
WHEN USED TOPICALLY IN EAR ... /NITROFURAZONE/ MAY PRODUCE CUTANEOUS SENSITIVITY REACTIONS. ... THIS TYPE OF REACTION ... FREQUENTLY MIMICS DISEASE BEING TREATED. ... /THIS DRUG REACTION/ CAN USUALLY BE RECOGNIZED BECAUSE THE INFLAMMATORY PROCESS BEGINS TO SPREAD TO LOBULE OF EAR & INFECTION DOES NOT RESPOND TO TREATMENT.
... STRAINS OF PSEUDOMONAS & PROTEUS ARE OFTEN RESISTANT.
IT HAS NOT YET BEEN SHOWN TO BE USEFUL IN TREATMENT OF MINOR BURNS, WOUNDS, OR CUTANEOUS ULCERS WHICH ARE INFECTED. IT IS PROBABLY NOT EFFECTIVE IN TREATMENT OF PYODERMA. ... APPROX 0.5-2% OF PATIENTS BECOME SENSITIZED TO DRUG, SOMETIMES WITHIN 5 DAYS OF INITIATION OF TREATMENT. ... FOR ALL NITROFURAZONE DOSAGE FORMS, AVOID EXPOSURE AT ALL TIMES TO DIRECT SUNLIGHT, EXCESSIVE HEAT & ALKALINE MATERIALS.
For more Drug Warnings (Complete) data for NITROFURAZONE (8 total), please visit the HSDB record page.

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Pharmacodynamics
Nitrofurazone is a topical antibacterial agent indicated as an adjunctive therapy for second and third degree burns when resistance to other agents is a real or potential problem. Nitrofurazone is also indicated in skin grafting when bacterial contamination may cause graft rejection or donor site infection, especially in hospitals with a history of resistant bacteria.

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.)