Nitazoxanide pharmacokinetics and tolerability in man using single ascending oral doses

Stockis, Armel; Allemon, A M; Bruyn, Steven De; Gengler, Christophe

doi:10.5414/cpp40213

Cited by 73 publications

(78 citation statements)

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“…Nevertheless, all patients completed the study, and no abnormalities of clinical chemistry parameters were related to its use. The adverse effects were very similar to those reported by other studies with NTZ in vivo (19,20), especially those noted by the patients taking a 1-g dose twice daily.…”

Section: Discussionsupporting

confidence: 88%

“…Previous studies showed that the incidence of adverse events was dose related, while vital signs, electrocardiograms, and laboratory test results remained unchanged (19). Side effects included loose stools, diarrhea, abdominal pain, flatulence, nausea, vomiting, dyspepsia, xerostomia, discolored urine (yellow-green), and headache (19,20).…”

mentioning

confidence: 97%

“…Side effects included loose stools, diarrhea, abdominal pain, flatulence, nausea, vomiting, dyspepsia, xerostomia, discolored urine (yellow-green), and headache (19,20).…”

mentioning

confidence: 99%

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Nitazoxanide in Treatment of Helicobacterpylori : a Clinical and In VitroStudy

Guttner

Windsor

Viiala

et al. 2003

Antimicrob Agents Chemother

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Nitazoxanide (NTZ) is an antibiotic with microbiological characteristics similar to those of metronidazole but without an apparent problem of resistance. The aim of this study was the prospective evaluation of NTZ given as a single agent in the treatment of Helicobacter pylori infection. Twenty culture-positive patients with dyspepsia who had previously failed at least one course of H. pylori eradication therapy were enrolled. Subjects received 1 g of NTZ twice daily for 10 days. The safety and tolerability of the drug were assessed by physical examination, monitoring of adverse events, and clinical laboratory evaluation. Urea breath tests (UBTs) were performed 6 weeks posttreatment. H. pylori was isolated from UBT-positive patients by the string test or endoscopy with biopsy, and the MICs for these isolates were compared to those for isolates obtained pretherapy. The levels of tizoxanide, the active deacylated derivative of NTZ, were measured in blood, saliva, and tissue from two patients during treatment. The UBT results were positive for all 20 patients after completion of NTZ therapy. The MIC results demonstrated that the NTZ susceptibilities of none of the strains isolated from the patients posttherapy had changed significantly. No major adverse reactions were observed, but frequent minor side effects were observed. In conclusion, NTZ did not eradicate H. pylori when it was given as a single agent.Nitazoxanide (NTZ), a nitrothiazolyl-salicylamide compound first described by Rossignol and Cavier (J. F. Rossignol and R. Cavier, Chem. Abstr. 83:28216n, 1975), has a broad spectrum of activity against microaerobic and anaerobic bacteria, anaerobic protozoa, and helminths (1, 6). It is the first antiparasitic agent reported to be effective against both protozoa and helminths, particularly in the treatment of intestinal parasitic infections (8, 13). The pharmacokinetics and metabolism of NTZ have been studied after the administration of single oral doses to healthy subjects (18), as well as after administration of radiocarbon-labeled NTZ (4). The main circulating metabolites have been identified as deacetyl-NTZ or tizoxanide (TIZ) and the corresponding acyl-glucuronide.Previous studies showed that the incidence of adverse events was dose related, while vital signs, electrocardiograms, and laboratory test results remained unchanged (19). Side effects included loose stools, diarrhea, abdominal pain, flatulence, nausea, vomiting, dyspepsia, xerostomia, discolored urine (yellow-green), and headache (19,20).NTZ was the first effective treatment for cryptosporidial diarrhea in patients with AIDS, eradicating Cryptosporidium parvum from the intestinal tract (5,7,14,21), and has been successful in the treatment of microsporidiosis in a patient with AIDS (3). Diarrhea caused by Giardia intestinalis and Entamoeba histolytica or Entamoeba dispar has also been shown to respond to NTZ (12,15). Furthermore, the drug was efficacious in a hamster model of antibiotic-induced diarrhea caused by Clostridium difficile compared to the...

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Section: Discussionsupporting

confidence: 88%

mentioning

confidence: 97%

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Nitazoxanide in Treatment of Helicobacterpylori : a Clinical and In VitroStudy

Guttner

Windsor

Viiala

et al. 2003

Antimicrob Agents Chemother

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“…The rocker was set to the following settings: 3 hours stationary, 15-minute rocking at a speed 5 rpm and maximum rocking angle 48 . The plates were incubated on the rocker in 37 C for 4 days.…”

Section: Spheroid Formationmentioning

confidence: 99%

Three-Dimensional Cell Culture-Based Screening Identifies the Anthelmintic Drug Nitazoxanide as a Candidate for Treatment of Colorectal Cancer

Senkowski

Zhang

Olofsson

et al. 2015

Molecular Cancer Therapeutics

133

149

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Because dormant cancer cells in hypoxic and nutrient-deprived regions of solid tumors provide a major obstacle to treatment, compounds targeting those cells might have clinical benefits. Here, we describe a high-throughput drug screening approach, using glucose-deprived multicellular tumor spheroids (MCTS) with inner hypoxia, to identify compounds that specifically target this cell population. We used a concept of drug repositioning-using known molecules for new indications. This is a promising strategy to identify molecules for rapid clinical advancement. By screening 1,600 compounds with documented clinical history, we aimed to identify candidates with unforeseen potential for repositioning as anticancer drugs. Our screen identified five molecules with pronounced MCTS-selective activity: nitazoxanide, niclosamide, closantel, pyrvinium pamoate, and salinomycin. Herein, we show that all five compounds inhibit mitochondrial respiration. This suggests that cancer cells in low glucose concentrations depend on oxidative phosphorylation rather than solely glycolysis. Importantly, continuous exposure to the compounds was required to achieve effective treatment. Nitazoxanide, an FDA-approved antiprotozoal drug with excellent pharmacokinetic and safety profile, is the only molecule among the screening hits that reaches high plasma concentrations persisting for up to a few hours after single oral dose. Nitazoxanide activated the AMPK pathway and downregulated c-Myc, mTOR, and Wnt signaling at clinically achievable concentrations. Nitazoxanide combined with the cytotoxic drug irinotecan showed anticancer activity in vivo. We here report that the FDA-approved anthelmintic drug nitazoxanide could be a potential candidate for advancement into cancer clinical trials.

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“…The recommended dose of NTZ is 500 mg in adults and adolescents, 200 mg in children aged 4-11 years and 100 mg in children aged 1-3 years; the dose was given twice daily for three days. (Stockis A et al 2002) The anthelmintic activity was tested against cestodes Maisonneuve H 1984, Stettler M et al 2003) as Taenia, Hymenolepis, Echinococcus, for trematodes as in Fasciola (Rossignol JF et al 1998, Favennec L et al 2003) and for nematodes , Diaz E et al 2003 as in Ascaris, Trichuris and Strongyloides with promising results. These advances prompted NTZ to be ranked as a broad-spectrum anthelmintic drug and eventually a broad-spectrum anti-parasitic drug (Fox LM …”

Section: Introductionmentioning

confidence: 99%

Comparative parasitological and electron microscopic studies on the effects of Nitazoxanide and Praziquantel in Schistosoma mansoni-infected mice

El-Taweel¹,

El-Sayad²,

Helw³

et al. 2016

IJPT

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This study was designed to evaluate antischistosomal activity of Nitazoxanide (NTZ) in Schistosoma mansoni-infected mice compared to Praziquantel (PZQ). Fifty four infected mice were recruited into 3 groups, each of 18 mice. Group 1 was infected non-treated control. Group 2 was infected and then treated with PZQ 500 mg for two days, and group 3 was infected and treated with NTZ 100 mg/kg for seven days. Efficacy of drugs was assessed by Parasitological, and scanning electron microscopic studies. PZQ reduced (4.9%, 22.5% and 50.7%) of faecal eggs, (22%, 22.6% and 55.1%) of intestinal eggs, (20.4%, 44.3% and 46.7%) of hepatic egg counts and (27%, 45.1% and 64.9%) of total worm load whereas, NTZ reduced (4.9%, 22.5% and 50.7%),of faecal eggs, (22%, 22.6% and 55.1%) of intestinal eggs ,(20.4%, 44.3% and 46.7%) of hepatic egg counts and (27%, 45.1% and 64.9%) of total worm load at 1, 2 and 4 WPT, respectively. The percentages of dead eggs were more than 80% after PZQ treatment and only 30% after NTZ at 4 WPT. PZQ showed extensive tegumental damages in male and female worms more than NTZ at 2 WPT. Our findings concluded that Nitazoxanide showed weaker antischistosomal activity in animal models than praziquantel.

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Nitazoxanide pharmacokinetics and tolerability in man using single ascending oral doses

Cited by 73 publications

References 0 publications

Nitazoxanide in Treatment of Helicobacterpylori : a Clinical and In VitroStudy

Nitazoxanide in Treatment of Helicobacterpylori : a Clinical and In VitroStudy

Three-Dimensional Cell Culture-Based Screening Identifies the Anthelmintic Drug Nitazoxanide as a Candidate for Treatment of Colorectal Cancer

Comparative parasitological and electron microscopic studies on the effects of Nitazoxanide and Praziquantel in Schistosoma mansoni-infected mice

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