| Identification | More | [Name]
Nitazoxanide | [CAS]
55981-09-4 | [Synonyms]
AURORA KA-645
NITAZOXANIDE
o-[n-(5-nitrothiazol-2-yl)carbamoyl]phenyl acetate
2-(acetolyloxy)-n-(5-nitro-2-thiazolyl)benzamide
2-(acetyloxy)-n-(5-nitro-2-thiazolyl)-benzamid
n-(5-nitro-2-thiazolyl)-salicylamidacetate(ester)
n-(5-nitro-2-thiazolyl)salicylamideacetate(ester)
nitazoxamide
PH-5776, Cryptaz, 2-(Acetyloxy)-N-(5-nitro-2-thiazolyl)benzamide
2-(Acetyloxy)-N-(5-nitro-2-thiazolyl)benzamide | [EINECS(EC#)]
259-931-8 | [Molecular Formula]
C12H9N3O5S | [MDL Number]
MFCD00416599 | [Molecular Weight]
307.28 | [MOL File]
55981-09-4.mol |
| Chemical Properties | Back Directory | [Appearance]
Crystalline Solid | [Melting point ]
202°C | [density ]
1.629 g/cm3 | [storage temp. ]
2-8°C | [solubility ]
Soluble in DMSO (>50 mg/ml) | [form ]
solid | [pka]
6.18±0.50(Predicted) | [color ]
Off-white | [Usage]
An anthelmintic (cestodes), antiprotozoal (cryptosporidium) | [λmax]
416nm(Phosphate buffer sol.)(lit.) | [Merck ]
14,6567 | [Stability:]
Stable for 2 years from date of purchase as supplied. Solutions in DMSO may be stored at -20°C for up to 3 months. | [CAS DataBase Reference]
55981-09-4(CAS DataBase Reference) |
| Safety Data | Back Directory | [Hazard Codes ]
Xn | [Risk Statements ]
22-36/37/38 | [Safety Statements ]
26-36 | [WGK Germany ]
3 | [RTECS ]
VN7830000 | [HS Code ]
2934100000 | [Toxicity]
LD50 orally in male, female mice: 1350, 1380 mg/kg; in rats: >10 g/kg (Murphy, Friedmann) |
| Hazard Information | Back Directory | [Description]
Nitazoxanide (NT Z) has been approved as an orphan drug for the treatment of diarrhea in children
(age, 1–11 years) and is associated with giardiasis, but it also is approved for diarrhea caused by
crytosporidiosis in patients with AIDS. Crytosporidiosis is a protozoal infection caused by
Cryptosporidi um parvum. The condition is uncommon in healthy individuals but can be
life-threatening in immunosuppressed patients and those with HIV infections. | [Chemical Properties]
Crystalline Solid | [Originator]
Alinia,Romark Laboratories, L.C. | [Uses]
An anthelmintic (cestodes), antiprotozoal (cryptosporidium). Kills Mycobacterium tuberculosis. | [Uses]
antihypertensive | [Uses]
For the treatment of diarrhea in adults and children caused by the protozoa Giardia lamblia and for the treatment of diarrhea in children caused by the protozoa Cryptosporidium parvum. | [Definition]
ChEBI: Acetic acid [2-[[(5-nitro-2-thiazolyl)amino]-oxomethyl]phenyl] ester is a carboxylic ester and a member of benzamides. It is functionally related to a salicylamide. | [Manufacturing Process]
To a solution containing one mole p-metoxy-benzoyl chloride and one mole of
carefully purified 2-amino-5-nitro-triazole in 200 ml of anhydrous
tetrahydrofuran, one mole of triethylamine has been slowly added (about 10
minutes) while stirring. The reaction mixture, which became slightly warm,
was stirred during 45 minutes and then poured under agitation, into 2 liters of
distilled water. The stirring was continued until the precipitation of
salicylamide, N-(5-nitro-2-thiazolyl)-, acetate (ester) was complete. The
obtained precipitate was dried, washed with water, dried again and
recrystallized from methanol. The yield about 60%; melting point 202°C. | [Brand name]
Alinia (Romark). | [Therapeutic Function]
Anthelmintic | [Antimicrobial activity]
In vitro Cryptosporidium parvum sporocytes and oocysts are
inhibited by <33 μm, and Giardia lamblia (intestinalis) trophozoites
by <10 μm. The metabolite tizoxanide is more active than
the parent compound against some isolates. E. histolytica is inhibited
by 6–23 μm (parent compound) and 5.6–
28 μm (metabolite),
and T. vaginalis by 0.5–15.5 μm (parent compound)
and 0.3–12.2 μm (metabolite). Activity against other micro-
organisms,
including some helminths, bacteria (Clostridium difficile)
and viruses (hepatitis C) has also been demonstrated. | [Acquired resistance]
Resistance caused by altered expression of genes involved in
stress response has been demonstrated in experimental studies
with G. lamblia. | [General Description]
Nitazoxanide (NTZ), a thiazolide compound is a antiparasitic drug with structure similar to niclosamide. | [Pharmaceutical Applications]
A synthetic broad-spectrum antiparasitic nitroheterocycle (2-acetyloxy-
N-(5-nitro-2-thiazolyl) benzamide), formulated for oral use. | [Biochem/physiol Actions]
Nitazoxanide is an inhibitor of pyruvate-ferredoxin oxidoreductase (PFOR); Antimicrobial recently found to kill both non-replicating and replicating mycobacteria. FDA approved anti-parasitic drug (2002). Recent work (C & EN Sept. 14, 2009, p. 28) highlights that NTZ kills non-replicating and replicating TB bacteria and no apparent resistance is detected. | [Mechanism of action]
Nitazoxanide is a pro-drug that is metabolically converted into the deactylated drug tizoxanide
(TIZ). The TIZ then undergoes a four-electron reduction of the 5-nitro group giving
various short-lived intermediates, which may include the hydroxylamine derivative. It is these
reduced products that represent the active form of NTZ. Whereas these intermediates would
suggest that NTZ has the same mechanism of action as metronidazole, this does not appear to be
the case. Nitazoxanide is thought to inhibit the enzyme pyruvate:ferredoxin oxidoreductase in
Trichomonas vaginali s, Entamoeba histolytica, and Cl ostridium perfingens. The results of this
inhibition is disruption of the bioenergetics of these organisms. Unlike metronidazole and
tinidazole, which fragment DNA and are suspected mutagenic agents, NTZ and TIZ do not cause
DNA fragmentation and are not considered to be mutagenic. This might be associated with the
higher redox potential found for NTZ, a nitrothiazole, in comparison with very low redox potential
found for the nitroimidazoles, such as metronidazole and tinidazole. Additional metabolites of TIZ
also includes the glucuronide, which shows some biological activity, and small amounts of an
aromatic hydroxylation product. | [Pharmacokinetics]
After oral administration the major circulating metabolites
are tizoxanide (desacetyl nitazoxanide) and its glucuronide.
Minor metabolites include salicyluric acid and tizoxanide sulfate.
Maximum concentrations of the active metabolites tizoxanide
and tizoxanide glucuronide are observed within 1–4 h.
Following a single oral dose of 500 mg given with food, the Cmax
of both metabolites was around 10 mg/L. Tizoxanide has a halflife
of around 1–2 h and is >99.9% bound to plasma proteins. | [Clinical Use]
It is indicated for the treatment of diarrhea caused by G. lamblia
or C. parvum. | [Side effects]
Nitazoxanide appears well tolerated. Side effects may include
abdominal pain diarrhea, headache and nausea. | [Veterinary Drugs and Treatments]
Nitazoxanide oral paste is indicated for the treatment of horses with
equine protozoal myeloencephalitis (EPM) caused by Sarcocystis
neurona.
In humans, nitazoxanide is approved (in the USA) for use in
treating diarrhea caused by Cryptosporidium parvum and Giardia
lamblia in pediatric patients from ages 1 to 11 years old.
Because of the drug’s spectrum of activity and apparent safety,
there is considerable interest in using it in a variety of companion
animal species, but data is lacking for specific indications and
dosages. | [Metabolism]
Nitazoxanide is available as powder that is reconstituted and dispensed as an oral suspension.
The drug is well absorbed from the GI tract and rapidly metabolized, with elimination products
appearing in the urine and feces. The only identified products in the plasma are TIZ and its
glucuronide. The product can be taken with food. | [storage]
Store at -20°C | [References]
References/Citations: |
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