Chemical Properties
solid
Definition
ChEBI: 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 us
d in the treatment of giardiasis and cholera.
Hazard
A questionable carcinogen, use has been
restricted.
Description
Furazolidone belongs to the group of nitro furans. This
antimicrobal (antibacterial and antiprotozoal) agent is
used in veterinary medicine both topically and orally,
particularly in animal feed. Reactions have been
reported in workers exposed to it by contact with
animal feed. Cross reactions with other nitrofuran
derivatives are rare.
Originator
Tricofuron,Norwich Eaton,US,1955
Manufacturing Process
In 212 cc of water are mixed 21.2 grams (0,112 mol) of N-(benzylidene)-3-
amino-2-oxazolidone, 8.93 grams of concentrated sulfuric acid, and 30.1
grams (0.124 mol) of 5-nitro-2-furaldehyde diacetate. This mixture is heated
to effect the hydrolysis of N-(benzylidene)-3-amino-2-oxazolidone, steam
distillation of the benzaldehyde and hydrolysis of 5-nitro-2-furaldehyde
diacetate. Approximately 1? hours are required for this reaction to take
place. When the bulk of the benzaldehyde has been removed, 50 cc of 99%
isopropanol are added, the reaction mixture is refluxed a short time, and the
crystals of N(5-nitro-2-furfurylidene)-3-amino-2-oxazolidone are filtered from
the hot suspension. The product is washed with water and isopropanol and
dried; a yield of 23.3 grams, 92.8% based on N-(benzylidene)-3-amino-2-
oxazolidone of MP 254° to 256°C is obtained, according to US Patent
2,759,931.
Brand name
Benilen;B-fsudi;Carbopuradin;Dapecfuran;Dectolin;Dialidene;Diarexin;Diarin;Diclofur;Doreplston;Dushel;Enterar;Enteroxon;Framenterol;Ft 15;Furaberin;Furacol l.;Furalatin p.;Furalidan;Furaliqua;Furoxona-cp;Fuvitan;Fuxol;Fuzatyl;Galacid;Gamafur s.;Giarlin;Ginvel;Injecur;Intefuran;Kalpec-f;Lacolysat;Mastisept;Multi-med 2;Multi-med 3;Multi-med 6;Neforox alpha cpto;Neftivit;Nicolen r;Nifulin;Parkestress forte;Saleton;Scantrimon;Sibren;Sirben;Syralbuna;Tetrafur;Tranatogen-ova;Ufa-cfo-400;Uterojekt;Vagifurona;Vetoprim;Vsf-medical g 15.
Therapeutic Function
Topical antiinfective
World Health Organization (WHO)
Furazolidone, a nitrofuran derivative with antibacterial and
antiprotozoal activity, was introduced in 1954. In the 1970s it was shown to have a
carcinogenic potential following long-term administration to experimental animals.
However, the relevance of this to short-term therapy in man has not been
established. The risk-benefit assessment varies and furazolidone remains widely
available in many countries for the treatment of diarrhoea and enteritis.
Antimicrobial activity
It is active against a wide range of enteric pathogens,
including Salmonella enterica, Shigella spp., enterotoxigenic
Escherichia coli, Campylobacter jejuni, Aeromonas hydrophila,
Plesiomonas shigelloides, Vibrio cholerae and V. parahaemolyticus.
Yersinia enterocolitica is intrinsically resistant. Furazolidone
is also active against the protozoa Giardia lamblia
and
Trichomonas vaginalis.
Acquired resistance
Acquired resistance has been observed in V. cholerae O1
and O139, S. enterica serotypes Typhi and Enteritidis,
A. hydrophila and Shigella spp. Such resistance may be
transferable, and there is cross-resistance with nitrofurantoin.
Many of these reports come from the Indian subcontinent,
where furazolidone is used widely for treating
diarrheal diseases.
General Description
Furazolidone is an effective antiprotozoal and antibacterial agent.
Pharmaceutical Applications
A non-ionic synthetic compound, available for oral use only.
It is poorly soluble in water (40 mg/L) and ethanol (90 mg/L),
but dissolves well in dimethylformamide (10 g/L). It decomposes
in the presence of alkali.
Biochem/physiol Actions
Furazolidone induces interstrand cross-links in subsequent mutation in bacterial cells. It also inhibits mono and diamine oxidase activities in eukaryotes.
Pharmacokinetics
There is substantial absorption (65–70%) after oral administration,
but the drug is heavily metabolized, so that only
about 5% of the material excreted is microbiologically active.
A dose of 5 mg/kg achieves a maximum plasma concentration
of around 1 mg/L. Protein binding is about 30%. Intact drug
can be found in various body fluids in concentrations approximating
to the minimum inhibitory concentration (MIC)
for various intestinal pathogens. Less than 1% of the drug is
excreted into urine.
Clinical Use
3-[(5-Nitrofurylidene)amino]-2-oxazolidinone (Furoxone)occurs as a yellow crystalline powder with a bitter aftertaste.It is insoluble in water or alcohol. Furazolidone hasbactericidal activity against a relatively broad range of intestinalpathogens, including S. aureus, E. coli, Salmonella,Shigella, Proteus spp., Enterobacter, and Vibrio cholerae.It is also active against the protozoan Giardia lamblia. It isrecommended for the oral treatment of bacterial or protozoaldiarrhea caused by susceptible organisms. The usualadult dosage is 100 mg 4 times daily.
Only a small fraction of an orally administered dose of furazolidoneis absorbed. Approximately 5% of the oral dose isdetectable in the urine in the form of several metabolites.Some gastrointestinal distress has been reported with its use.Alcohol should be avoided when furazolidone is being usedbecause the drug can inhibit aldehyde dehydrogenase.
Clinical Use
Furazolidone is used in gastrointestinal infections and vaginitis.
It is mainly used in developing countries to treat diarrheal
diseases of varying etiology, but it is not the drug of choice
if a specific pathogen has been identified. Use as a secondline
agent in giardiasis and as part of multidrug regimens in
Helicobacter infection has been advocated.
Side effects
Most reported side effects are mild and only rarely cause discontinuation
of treatment. Nausea and vomiting are experienced
by around 8% of patients. Other adverse events include
neurological reactions (mainly headache; 1.3% of patients),
‘systemic’ reactions such as fever and malaise (0.6%) and skin rashes (0.54%). Administration of furazolidone may give rise
to inhibition of monoamine oxidase, and disulfiram-like reactions
have been reported.
Synthesis
Furazolidone, 3-(5-nitrofurfuryliden)amino-2-oxazolidinone (33.7.8), is
synthesized from 2-hydroazinoethanol, which is reacted with diethyloxalate to make 3-
amino-2-oxazolidone. Reacting this with benzaldehyde gives the corresponding hydrazone
(33.3.7). Purifying the resulting product and then reacting it with 5-nitrofurfurol gives
furazolidone.
Veterinary Drugs and Treatments
Furazolidone is usually a drug of second choice in small animals
to treat enteric infections caused by the organisms listed below.
Because it is no longer commercially available (in the USA), it may
be difficult to locate.
