o-[N-(5-Nitrothiazol-2-yl)carbamoyl]phenylacetat Chemische Eigenschaften,Einsatz,Produktion Methoden
Beschreibung
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.
Chemische Eigenschaften
Crystalline Solid
Verwenden
Nitazoxanide has been used:
- to test its anti-viral activity against chikungunya virus
- as an antiprotozoal agent to test its effect on cell viability in various cancer cell lines
- to test its effect on human cytomegalovirus (HCMV) infected human fibroblast HFF cells
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.
Allgemeine Beschreibung
Nitazoxanide (NTZ), a thiazolide compound is a antiparasitic drug with structure similar to niclosamide.
Pharmazeutische Anwendungen
A synthetic broad-spectrum antiparasitic nitroheterocycle (2-acetyloxy-
N-(5-nitro-2-thiazolyl) benzamide), formulated for oral use.
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.
Pharmakokinetik
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 C
max
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.
Nebenwirkungen
Nitazoxanide appears well tolerated. Side effects may include
abdominal pain diarrhea, headache and nausea.
Stoffwechsel
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.
o-[N-(5-Nitrothiazol-2-yl)carbamoyl]phenylacetat Upstream-Materialien And Downstream Produkte
Upstream-Materialien
Downstream Produkte
