HIV-1; HBV/HCV (EC50 = 0.46μM and 0.15 μM)

Tizoxanide is the active metabolite of Nitazoxanide, which is a thiazolide anti-infective compound against anaerobic bacteria, protozoa, and a range of viruses. IC50 value: Target: Antiviral agent in vitro: Tizoxanide inhibited virus replication of all CIVs with 50% and 90% inhibitory concentrations ranging from 0.17 to 0.21 μM and from 0.60 to 0.76 μM, respectively. Nitazoxanide and its primary metabolite, tizoxanide, inhibit hepatitis C virus (HCV) replication in HCV replicon systems. Interestingly, serial passage in nitazoxanide or tizoxanide resulted in increased sensitivity to alpha interferon 2b: EC(50)s and EC(90)s were reduced three- and eightfold, respectively.

Nitazoxanide is partially effective at reducing the parasite burden in a gnotobiotic piglet diarrhea model when given orally for 11 days at 250 mg/kg/day but not at 125 mg/kg/day. Nitazoxanide induces a drug-related diarrhea in piglets that might have influenced its therapeutic efficacy.

Metabolism / Metabolites
Tizoxanide has known human metabolites that include (2S,3S,4S,5R)-3,4,5-Trihydroxy-6-[2-[(5-nitro-1,3-thiazol-2-yl)carbamoyl]phenoxy]oxane-2-carboxylic acid.

[1]. Antimicrob Agents Chemother.1998 Aug;42(8):1959-65.

[2]. Clin Infect Dis.2005 Apr 15;40(8):1173-80.

Desacetyl-nitazoxanide is a member of salicylamides.

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Nitazoxanide (NTZ), a drug currently being tested in human clinical trials for efficacy against chronic cryptosporidiosis, was assessed in cell culture and in two animal models. The inhibitory activity of NTZ was compared with that of paromomycin (PRM), a drug that is partially effective against Cryptosporidium parvum. A concentration of 10 microg of NTZ/ml (32 microM) consistently reduced parasite growth in cell culture by more than 90% with little evidence of drug-associated cytotoxicity, in contrast to an 80% reduction produced by PRM at 2,000 microg/ml (3.2 mM). In contrast to its efficacy in vitro, NTZ at either 100 or 200 mg/kg of body weight/day for 10 days was ineffective at reducing the parasite burden in C. parvum-infected, anti-gamma-interferon-conditioned SCID mice. Combined treatment with NTZ and PRM was no more effective than treatment with PRM alone. Finally, NTZ was partially effective at reducing the parasite burden in a gnotobiotic piglet diarrhea model when given orally for 11 days at 250 mg/kg/day but not at 125 mg/kg/day. However, the higher dose of NTZ induced a drug-related diarrhea in piglets that might have influenced its therapeutic efficacy. As we have previously reported, PRM was effective at markedly reducing the parasite burden in piglets at a dosage of 500 mg/kg/day. Our results indicate that of all of the models tested, the piglet diarrhea model most closely mimics the partial response to NTZ treatment reported to occur in patients with chronic cryptosporidiosis. [1]

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Nitazoxanide is a new thiazolide antiparasitic agent that shows excellent in vitro activity against a wide variety of protozoa and helminths. It is given by the oral route with good bioavailability and is well tolerated, with primarily mild gastrointestinal side effects. At present, there are no documented drug-drug interactions. Nitazoxanide has been licensed for the treatment of Giardia intestinalis-induced diarrhea in patients >or=1 year of age and Cryptosporidum-induced diarrhea in children aged 1-11 years. At present, it is pending licensure for treatment of infection due to Cryptosporidium species in adults and for use in treating immunocompromised hosts. It represents an important addition to the antiparasitic arsenal. [2]

C10H7N3O4S

265.25

265.015

C, 45.28; H, 2.66; N, 15.84; O, 24.13; S, 12.09

173903-47-4

Tizoxanide-d4;1246817-56-0

394397

Solid powder

1.6±0.1 g/cm3

279-281ºC(dec)

1.750

2.91

2

6

2

18

336

0

S1C(=C([H])N=C1N([H])C(C1=C([H])C([H])=C([H])C([H])=C1O[H])=O)[N+](=O)[O-]

FDTZUTSGGSRHQF-UHFFFAOYSA-N

InChI=1S/C10H7N3O4S/c14-7-4-2-1-3-6(7)9(15)12-10-11-5-8(18-10)13(16)17/h1-5,14H,(H,11,12,15)

2-hydroxy-N-(5-nitrothiazol-2-yl)benzamide

NSC-697856; NSC697856; Tizoxanide; 173903-47-4; 2-hydroxy-N-(5-nitrothiazol-2-yl)benzamide; Benzamide, 2-hydroxy-N-(5-nitro-2-thiazolyl)-; Desacetyl-nitazoxanide; NSC-697856; 2-hydroxy-N-(5-nitro-1,3-thiazol-2-yl)benzamide; UNII-15KFG88UOJ; NSC697856; Tizoxanide; Desacetylnitazoxanide; Desacetyl-nitazoxanide;

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 : ~25 mg/mL (~94.25 mM)
Ethanol : < 1 mg/mL

Solubility in Formulation 1: 5 mg/mL (18.85 mM) in 15% Cremophor EL + 85% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication (<60°C).
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: 15% Cremophor EL+85% Saline: 5 mg/mL (18.85 mM)

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Solubility in Formulation 3: 5 mg/mL (18.85 mM) in 17% Polyethylene glycol 12-hydroxystearate in Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication (<60°C).
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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 (Please use freshly prepared in vivo formulations for optimal results.)