Oral Nitazoxanide Research Articles

The antiprotozoal drug nitazoxanide improves experimental liver fibrosis in mice

Nitazoxanide is an FDA-approved antiprotozoal drug. Our previous studies find that nitazoxanide and its metabolite tizoxanide affect AMPK, STAT3, and Smad2/3 signals which are involved in the pathogenesis of liver fibrosis, therefore, in the present study, we examined the effect of nitazoxanide on experimental liver fibrosis and elucidated the potential mechanisms. The in vivo experiment results showed that oral nitazoxanide (75, 100 mg·kg−1) significantly improved CCl4- and bile duct ligation-induced liver fibrosis in mice. Oral nitazoxanide activated the inhibited AMPK and inhibited the activated STAT3 in liver tissues from liver fibrosis mice. The in vitro experiment results showed that nitazoxanide and its metabolite tizoxanide activated AMPK and inhibited STAT3 signals in LX-2 cells (human hepatic stellate cells). Nitazoxanide and tizoxanide inhibited cell proliferation and collagen I expression and secretion of LX-2 cells. Nitazoxanide and tizoxanide inhibited transforming growth factor-β1 (TGF-β1)- and IL-6-induced increases of cell proliferation, collagen I expression and secretion, inhibited TGF-β1- and IL-6-induced STAT3 and Smad2/3 activation in LX-2 cells. In mouse primary hepatic stellate cells, nitazoxanide and tizoxanide also activated AMPK, inhibited STAT3 and Smad2/3 activation, inhibited cell proliferation, collagen I expression and secretion. In conclusion, nitazoxanide inhibits liver fibrosis and the underlying mechanisms involve AMPK activation, and STAT3 and Smad2/3 inhibition.

The clinical antiprotozoal drug nitazoxanide and its metabolite tizoxanide extend Caenorhabditis elegans lifespan and healthspan

The drugs extending healthspan in clinic have always been searched. Nitazoxanide is an FDA-approved clinical antiprotozoal drug. Nitazoxanide is rapidly metabolized to tizoxanide after absorption in vivo. Our previous studies find that nitazoxanide and its metabolite tizoxanide induce mild mitochondrial uncoupling and activate cellular AMPK, oral nitazoxanide protects against experimental hyperlipidemia, hepatic steatosis, and atherosclerosis. Here, we demonstrate that both nitazoxanide and tizoxanide extend the lifespan and healthspan of Caenorhabditis elegans through Akt/AMPK/sir 2.1/daf16 pathway. Additionally, both nitazoxanide and tizoxanide improve high glucose-induced shortening of C. elegans lifespan. Nitazoxanide has been a clinical drug with a good safety profile, we suggest that it is a novel anti-aging drug.

Atazanavir/Ritonavir Increased Tizoxanide Exposure from Oral Nitazoxanide through Pharmacokinetic Interaction in Healthy Volunteers

Nitazoxanide use is limited by gastrointestinal side effects associated with increasing dose. In this drug repurposing study, we investigated the possibility of enhancing the exposure of its active metabolite, tizoxanide, through pharmacokinetic interaction with atazanavir/ritonavir. In this crossover drug–drug interaction study, 18 healthy participants received a single dose of 1000 mg of nitazoxanide alone and in combination with 300/100 mg atazanavir/ritonavir in period 1 and 2 respectively. On both days, blood samples for intensive pharmacokinetic analyses were collected at 0–12 h post-dose. To explore the utility of dried blood spots (DBS) as an alternative to plasma for tizoxanide quantification, 50 µL of blood from some participants was spotted on DBS cards and correlated with plasma concentrations. Pharmacokinetic parameters were derived by non-compartmental analysis and compared between both periods. Co-administration of nitazoxanide with atazanavir/ritonavir resulted in a significant increase in tizoxanide plasma exposure [GMR (90% CI) of AUC0–12h, Cmax and C12h being 1.872 (1.870–1.875), 2.029 (1.99–2.07) and 3.14 (2.268–4.352), respectively]. DBS concentration (%CV) was 46.3% (5.6%) lower than plasma concentrations, and there was strong correlation (R = 0.95, p < 0.001) between DBS-derived plasma concentration and plasma concentrations. Co-administration with atazanavir/ritonavir enhanced tizoxanide exposure with no report of adverse events in healthy volunteers.

An Unusual Case of Liver Abscess Caused by Trematodes

Liver abscess caused by trematodes is considered highly unusual. Here we present a case of an elderly female with no knowncomorbidities, who presented with fever and right upper quadrant pain. Upon evaluation, she was found to have features ofliver abscess on abdominal ultrasound and 640-slice computed tomography (CT) of the abdomen. Ultrasound-guided needlebiopsy of the liver showed features of trematode. Patient was treated with oral nitazoxanide. Patient’s fever and abdominalpain subsided after the treatment.

Chronic norovirus infection in a pediatric patient with complete DiGeorge syndrome

Infectious gastroenteritis is a common acute illness that is usually self-limiting. Norovirus, in particular, is a common cause of acute gastroenteritis. In immunocompromised patients, however, norovirus infection may progress to prolonged viral shedding leading to debilitating and life-threatening consequences.A 3-year-old boy with congenital athymia and resulting severe T cell lymphopenia secondary to complete DiGeorge syndrome presented with acute worsening of chronic diarrhea. Previous work up for his chronic diarrhea included negative infectious and malabsorption studies. When he presented with acute worsening of diarrhea, work up included lymphocyte analysis that demonstrated stable severe T cell lymphopenia and infectious studies that were positive for norovirus. The patient had large volume diarrhea requiring hospital admission for intravenous fluids to manage dehydration and electrolyte derangements.Given the degree of immunocompromised and the risk for severe and chronic norovirus infection in this patient with complete DiGeorge syndrome, different therapeutic options were evaluated. The patient was started on oral immunoglobulin therapy 100 mg/kg three times per week as well as oral nitazoxanide 100 mg twice daily. Oral immunoglobulin therapy was discontinued after 2 months due to lack of perceived benefit. On days patient missed a dose of nitazoxanide, worsening of diarrhea was observed. Nitazoxanide therapy was continued given clear symptomatic benefit.While he experienced decreased number of bowel movements on nitazoxanide, his continued symptoms led to progressive weight loss, with a 12% decrease in body weight two months after norovirus diagnosis. Metronidazole was considered but was not initiated because concerns for side effects outweighed the evidence for benefit for this patient. Stool studies at this time demonstrated presence of fecal fat, consistent with malabsorption. The patient was subsequently started on total parental nutrition. His malabsorption and diarrhea persisted but he has been able to gain weight.This case demonstrates how severe norovirus infection can present in immunodeficient patients, specifically those with severe T cell lymphopenia. Moreover, this case highlights the need for research in therapeutics for the treatment of chronic norovirus infection in immunodeficient patients.

Nitazoxanide in Acute Rotavirus Diarrhea- A Randomized Controlled Trial Study in a Tertiary Care Hospital in Bangladesh

Background: Acute rotavirus diarrhea is one of the leading cause of morbidity and mortality in children younger than 5 years. Nitazoxanide, an antiparasitic agent, acts by inhibiting the maturation of rotavirus viral protein 7 thus interferes with viral morphogenesis. Aim of the study: was to evaluate the role of nitazoxanide in the treatment of acute rotavirus diarrhea in 6 months to 2 years aged children. Methods: This randomized controlled trial was conducted at Bangladesh Shishu Hospital & Institute, Dhaka, Bangladesh from June 2018 to July 2020. A total of 70 children with acute onset diarrhea of <48 hours. duration was included in this study. All the studied patients were divided into two equal groups (group I and group II) by lottery, each comprising 35 children. The groupI represented the study group who received standard treatment of diarrhea plus oral nitazoxanide (15mg/kg/day) twice daily for 3 days and the group II is the control group received standard treatment only. Results: Study demonstrated that maximum number of patients 22 (31.4%) were between 14-17 months of age group and 36% patients came from rural, 64% from urban areas. Study showed before commencement of treatment most of the patients in both groups experienced some dehydration, vomiting, fever, & abdominal distension. At 48 hours’ improvement was observed in both groups, comparatively higher in group I. Difference of some dehydration and vomiting improvement between two groups were statistically significant (p <0.05). After 3 days’ treatment normal stool consistency was found in 24(68.5%) patients in group I & 10 (28.5%) in group II patients. The difference was also statistically significant (p=<0.05). Mean time of resolution of diarrhea 62.5 hours in Group-I and 96.5 hours in group-II. Compared to the group II, group I showed decrease in mean time of resolution of diarrhea (p= 0.001). The mean duration of hospital stay was prolonged in group-II (86.5 hours vs. 102.5 hours in group I & II respectively), the difference was statistically significant (p˂0.05). Conclusion: In the present study, oral nitazoxanide was found effective in the treatment of acute rotavirus diarrhea in 6 months to 2 years old children.

A randomized double-blind placebo-controlled clinical trial of nitazoxanide for treatment of mild or moderate COVID-19.

SummaryBackgroundThere is an urgent need for treatments of mild or moderate COVID-19 in an outpatient setting.MethodsA randomized double-blind placebo-controlled clinical trial in 36 centers in the U.S. between August 2020 and February 2021 investigated the safety and effectiveness of oral nitazoxanide 600 mg twice daily for five days in outpatients with symptoms of mild or moderate COVID-19 enrolled within 72 h of symptom onset (ClinicalTrials.gov NCT04486313). Efficacy endpoints were time to sustained clinical recovery (TSR, a novel primary endpoint) and proportion of participants progressing to severe illness within 28 days (key secondary).Findings1092 participants were enrolled. 379 with laboratory-confirmed SARS-CoV-2 infection were analyzed. In the primary analysis, median (IQR) TSR were 13·3 (6·3, >21) and 12·4 (7·2, >21) days for the nitazoxanide and placebo groups, respectively (p = 0·88). 1 of 184 (0·5%) treated with nitazoxanide progressed to severe illness compared to 7 of 195 (3·6%) treated with placebo (key secondary analysis, odds ratio 5·6 [95% CI 0·7 - 46·1], relative risk reduction 85%, p = 0·07). In the pre-defined stratum with mild illness at baseline, nitazoxanide-treated participants experienced reductions in median TSR (3·1 days, p = 0·09) and usual health (5·2 days, p < 0·01) compared to placebo. Nitazoxanide was safe and well tolerated.InterpretationFurther trials with larger numbers are warranted to evaluate efficacy of nitazoxanide therapy in preventing progression to severe illness in patients at high risk of severe illness and reducing TSR in patients with mild illness.

Early Treatment With Nitazoxanide Prevents Worsening of Mild and Moderate COVID-19 and Subsequent Hospitalization

Background: There is an urgent need for treatments to prevent the progression to severe COVID-19 and hospitalization.Methods: This is a double-blind randomized multicenter study in 36 centers in the U.S. and Puerto Rico investigating the potential of a five-day treatment with nitazoxanide 300 mg extended release tablets in 379 outpatients with mild or moderate laboratory-confirmed COVID-19 with an onset of symptoms no more than 72 hours before inclusion. Key objectives were reduction of duration of symptoms, progression to severe illness, hospitalization and viral load.Results: Time to sustained response was not reduced by nitazoxanide (median: 13.28 and 12.35 days for nitazoxanide and placebo). Nitazoxanide treatment provided an 85% reduction in the progression to severe COVID-19 (1/184, [0.5%] nitazoxanide vs. 7/195, [3.6%] placebo). In subjects at high-risk according to CDC criteria, 1/112 (0.9%) of nitazoxanide-treated subjects and 7/126 (5.6%) of placebo-treated subjects experienced progression to severe COVID-19. Treatment led to a 79% reduction in the rate of hospitalization (1/184 [0.5%] nitazoxanide vs. 5/195 [2.6%] placebo). The proportions positive for SARS-CoV-2 RNA and viral load at days 4 and 10 were not reduced. Nitazoxanide was safe and well tolerated.Conclusions: Treatment of mild or moderate COVID-19 with a five-day course of oral nitazoxanide was safe and well tolerated and was associated with an 85% reduction in the progression to severe illness. The availability of a safe, oral, scalable, host-directed antiviral for the early treatment of COVID-19 could play an important role in reducing the number of severe illnesses and hospitalizations during this ongoing major public health crisis.Trial Registration Details: ClinicalTrials.gov Identifier: NCT04486313.Funding Information: This study was funded by the Romark Institute of Medical Research.Declaration of Interests: Jean-Francois Rossignol is an employee of and owns equity interest in Romark, L.C. Matthew Bardin, Jessica Fulgencio and Dena Mogelnicki are employees of Romark, L.C.; Christian Brechot is a senior adviser for Romark, L.C., an adviser for the Theravectys, Shanghai Vivo Biosciences and the chairman of The Healthy Aging company. Ethics Approval Statement: The central institutional review board (IRB) or a local IRB at each center approved the protocol.

Oral nitazoxanide treatment of experimental neurocysticercosis induces gluconeogenesis in Taenia crassiceps cysticerci

Neurocysticercosis is the most frequent helminthiasis of the central nervous system and is caused by the presence of Taenia solium cysticerci. Nitazoxanide (NTZ) is an antifolate containing the pyrrolopyrimidine-based nucleus that exerts its antiprotozoal activity due to interference with the pyruvate:ferredoxin oxidoreductase (PFOR) enzyme which is essential to anaerobic energy metabolism. The aim of this work was to determine the effect of NTZ on the energetic metabolism of Taenia crassiceps cysticerci intracranially inoculated BALB /c mice. The infected animals were treated with a single oral dose of NTZ 30 days after the inoculation. Analysis of the organic acids was performed through high performance liquid chromatography. Glucose was detected only in the treated groups, alongside with a significant decrease in lactate, pyruvate and oxaloacetate concentrations which indicate an increase in gluconeogenesis. The non-detection of alpha-ketoglutarate indicated the use of the fumarate reductase pathway in all groups. It was possible to confirm the drugs mode of action due to the non-detection of acetate in the treated groups. There was an increase in the fatty acids oxidation. Therefore it was possible to observe that NTZ induces gluconeogenesis as well as the increase of alternative energetic pathways such as fatty acids oxidation in T. crassiceps cysticerci.

578 - Use of Nitazoxanide, an Anti-Parasitic Drug, for Management of Norovirus Ileo-Colitis in an Allogeneic Stem Cell Transplant Patient

Patients undergoing allogeneic stem cell transplant are at significant risk of infections due to the immunosuppression resulting from leukopenia as well as immunosuppressive agents for graft versus host disease prophylaxis or management. Organisms that normally do not result in significant clinical manifestations can cause potentially lethal outcomes in infected allogeneic stem cell transplant patients. Diarrhea resulting from infectious etiology continues to remain a significant complication associated with allogeneic stem cell transplant. Norovirus gastroenteritis is a well described phenomenon in both pediatric as well as adult allogeneic hematopoietic stem cell transplant recipients. There is no definite treatment available for managing this complication and supportive care and withdrawal of immunosuppression continues to remain the mainstay. We report the case of a 68-year-old Caucasian female who underwent a haplo-identical stem cell transplant for high-risk acute myeloid leukemia with FLT3 mutation. The patient developed diarrhea on day+4 and her stool tested positive for Clostridium difficile. Even though she initially responded to appropriate treatment for Clostridium difficile, her diarrhea recurred. Repeat testing for infectious etiology revealed the presence of norovirus while Clostridium difficile was no longer detected. The patient was treated with oral nitazoxanide 500 mg BID for 10 days with significant clinical improvement in her stool volume and frequency as well as consistency. However, she continued to shed the virus even after clinical improvement. Nitazoxanide was developed in 1970 and was initially perceived to be an anti-protozoal agent. An increasing amount of pre-clinical and clinical research has indicated that it is active against a broad variety of organisms including anaerobic gram-positive and gram-negative bacteria, mycobacterium tuberculosis, respiratory viruses as well as rotavirus and norovirus. While there is literature supporting the use of nitazoxanide in other immunosuppressed patients such as HIV infected and solid organ transplant patients, information regarding the safety and efficacy of nitazoxanide for treating norovirus in adult allogeneic stem cell transplant patients is very limited (one case report identified in Pubmed). Our case demonstrates that even in early post-transplant setting, nitazoxanide effectively controlled norovirus gastroenteritis without compromising graft function. The utility of Nitazoxanide in viral gastroenteritis in allogeneic hematopoietic transplant patients should be explored further in prospective trials.Tabled 1Pubmed search using the terms “Nitazoxanide” AND one of the following# of Items in search resultsRelevant to clinical use of Nitazoxanide for Norovirus in Hematopoietic Stem Cell transplantHematopoietic transplant31Stem cell transplant51Norovirus101 Open table in a new tab

The NICE-GUT trial protocol: a randomised, placebo controlled trial of oral nitazoxanide for the empiric treatment of acute gastroenteritis among Australian Aboriginal children

IntroductionDiarrhoeal disease is the second leading cause of death in children under 5 years globally, killing 525 000 annually. Australian Aboriginal and Torres Strait Islander (hereafter Aboriginal) children suffer a...

Inhibition of rubella virus replication by the broad-spectrum drug nitazoxanide in cell culture and in a patient with a primary immune deficiency

Persistent rubella virus (RV) infection has been associated with various pathologies such as congenital rubella syndrome, Fuchs's uveitis, and cutaneous granulomas in patients with primary immune deficiencies (PID). Currently there are no drugs to treat RV infections. Nitazoxanide (NTZ) is an FDA-approved drug for parasitic infections, and has been recently shown to have broad-spectrum antiviral activities. Here we found that empiric 2-month therapy with oral NTZ was associated in the decline/elimination of RV antigen from lesions in a PID patient with RV positive granulomas, while peginterferon treatment had no effect. In addition, we characterized the effects of NTZ on cell culture models of persistent RV infection. NTZ significantly inhibited RV replication in a primary culture of human umbilical vein endothelial cells (HUVEC) and Vero and A549 epithelial cell lines in a dose dependent manner with an average 50% inhibitory concentration of 0.35 μg/ml (1.1 μM). RV strains representing currently circulating genotypes were inhibited to a similar extent. NTZ affected early and late stages of infection by inhibiting synthesis of cellular and RV RNA and interfering with intracellular trafficking of the RV surface glycoproteins, E1 and E2. These results suggest a potential application of NTZ for the treatment of persistent rubella infections, but more studies are required.

Nitazoxanide in Acute Rotavirus Diarrhea: A Randomized Control Trial from a Developing Country.

Background. Acute diarrhea is one of the leading causes of childhood mortality, with rotavirus being an important pathogen. Nitazoxanide, an antiparasitic agent, has been shown to inhibit rotavirus. Objective. This double-blind, randomized trial was designed to study the role of nitazoxanide in acute rotavirus diarrhea. Methods. Of 174 children (12 months to 5 years) with acute diarrhea, 50 rotavirus positive cases were randomized. The intervention group received syrup nitazoxanide twice daily (100 mg in 12–47 months, 200 mg in ≥4 yr) for 3 days along with standard treatment of diarrhea. Duration of diarrhea was the primary outcome measure. Results. The median duration (hrs) of diarrhea (54 versus 80; 95% CI: –26 [–13.2 to –38.8]) and hospitalization (68 versus 90; 95% CI: –22 [–12.98 to –31.02]) was significantly shorter in the nitazoxanide group. No significant difference was seen in the median duration (hrs) of fever or vomiting or the proportion of children requiring parenteral rehydration. There was no report of any adverse events. Conclusions. Oral nitazoxanide is effective and safe in the management of acute rotavirus diarrhea in Indian children (CTRI REF/2016/10/012507).

Nitazoxanide: In vitro and in vivo drug effects against Trichuris muris and Ancylostoma ceylanicum, alone or in combination

Soil-transmitted helminths cause more than 1billion human infections globally, mostly in the poorest regions of the world. Control relies essentially on a limited panel of four drugs, and drug resistance might be inescapable. Nitazoxanide, an anti-infective drug, has been shown to exert anthelmintic activity in human clinical trials. In the present work, nitazoxanide was tested alone or combined with commercialized anthelmintics on Trichuris muris, a whipworm mouse model, and Ancylostoma ceylanicum, a hookworm hamster model, in vitro and in vivo. IC50s of ⩽1 and 12.87μg/ml were achieved with nitazoxanide on T. muris third-stage larvae (L3) and adult worms in vitro, respectively. An IC50 of ⩽1μg/ml was obtained exposing A. ceylanicum adults worms to nitazoxanide, whereas A. ceylanicum L3 were not affected. Using scanning electron microscopy, the tegument of adult T. muris appeared unchanged following nitazoxanide treatment, whereas swellings were seen on the tegument of the anterior region of half of the A. ceylanicum specimen analyzed. Synergism was observed in vitro when nitazoxanide was combined with levamisole or ivermectin on T. muris adult worms, and when combined with levamisole, pyrantel pamoate, or ivermectin on A. ceylanicum adult worms. In T. muris-infected mice, oral nitazoxanide achieved worm burden reductions of 56.09% and 17.37% following a single dose of 100mg/kg and three doses of 50mg/kg, respectively. None of the tested drug combinations displayed activity on T. muris in vivo. In A. ceylanicum-infected hamsters, no effect was observed for oral nitazoxanide alone, and none of the tested combinations reached the threshold for additive effect. In conclusion, nitazoxanide failed to demonstrate promising activity against T. muris and A. ceylanicum in vivo, regardless whether tested as monotherapy or combined with standard drugs. Reasons for the discrepancy of these findings compared to results obtained in clinical trials remain to be elucidated.

Symptomatic Trichomonas vaginalis infection in the setting of severe nitroimidazole allergy: successful treatment with boric acid

This report describes a patient with symptomatic Trichomonas vaginalis infection who was unable to tolerate nitroimidazole drugs because of severe hypersensitivity, for which desensitisation was not possible. Use of intravaginal clotrimazole, intravaginal paromomycin, intravaginal furazolidone, povidone-iodine douches, and oral nitazoxanide were unsuccessful in eradicating the patient's T. vaginalis infection. A 2-month course of intravaginal topical boric acid subsequently achieved a complete symptomatic cure and the patient remained T. vaginalis wet prep- and culture-negative 60 days after treatment.

Intervention to prevent intestinal parasitic reinfections among Tarahumara indigenous schoolchildren in northern Mexico

To assess the effectiveness of a 20-week, broad intervention to prevent reinfection by Ascaris lumbricoides (AL) and Giardia lamblia (GL) among indigenous schoolchildren in northern Mexico. A prospective, comparative, ecological study. Two isolated boarding schools, each hosting 100-120 children, 4-15 years of age, were selected based on physical infrastructure: intervention school (IS), modern; control school (CS), deprived. After initial diagnosis, children with positive stool samples received supervised treatment with oral nitazoxanide. Diagnoses were made with at least one positive microscopic result from two serial samples using the Faust technique, as reported by the independent observations of two trained, laboratory technicians. Post-treatment samples were taken, and only those with negative results were followed-up. The intervention included infrastructure improvements/maintenance and an educational preventive program for children, parents, and school personnel; no activities were undertaken in the CS. Baseline prevalence for AL was 37.5% at the IS versus 16.6% at the CS (P < 0.01); and for GL, 51.7% versus 37.8%, respectively. At the IS, 35.7% did not speak Spanish, compared to 6.7% in the CS (P < 0.01). Cure rates were similar in both schools for AL (~ 98%) and GL (~ 80%). Final prevalence and reinfection rates for GL were 10.4% versus 10.8%, and 17.2% versus 21% at the IS and CS, respectively. No children were infected/reinfected with AL in either school. Follow-up rates were 80%-83% at the CS and 90%-95% at the IS. Infection/reinfection rates were similar at the schools after 20 weeks. Supervised treatment alone every semester could effectively control AL/GL infections in this indigenous setting.

Bioavailability of Two Oral-Suspension Formulations of a Single Dose of Nitazoxanide 500 mg: An Open-Label, Randomized-Sequence, Two-Period Crossover, Comparison in Healthy Fasted Mexican Adult Volunteers

Nitazoxanide is an oral broad-spectrum parasiticidal agent. In Mexico, the oral powder for suspension of nitazoxanide is indicated for the treatment of antiprotozoal and anthelmintic infections in patients of 1 year or older. The aims of this study were to compare the bioavailability and to determine the bioequivalence of a test and reference formulation of oral nitazoxanide 500 mg, administered as a suspension, and to generate data regarding the oral bioavailability of this drug on the Mexican population. This single-dose, randomized-sequence, open-label, 2-period crossover study was conducted on a total of 26 Mexican adult subjects of both genders, with a 1-week washout period. Study formulations were administered after a 10-hour overnight fast. For pharmacokinetic analysis, blood samples were drawn at 0 (baseline), 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, 10 and 12 hours after administration. Plasma concentrations of tizoxanide (active metabolite of nitazoxanide) were determined using HPLC coupled to a mass spectrometry (MS/MS). The test and reference formulations were to be considered bioequivalent if the 90% CIs for the geometric mean test/reference ratios were within a predetermined range of 80% to 125%. The estimated pharmacokinetic parameters of tizoxanide for the reference (Daxon ® ) and test (Paramix ® ) formulations were: C max (10.40±2.99 μg/ml, 10.73 ± 3.45 μg/ml); AUC 0–t (39.57 ± 15.89 μg•h /ml, 43.31 ± 19.13 μg•h / ml); and AUC 0–∞ (40.93 ± 16.05 μg•h /ml, 45.00 ± 19.63 μg•h /ml), respectively. The 90% CIs for the geometric mean ratios of C max, AUC 0–t, and AUC 0–∞ were: 94.58%-110.21%, 100.43%-116.22%, and 101.00%-116.43%, respectively, the within-subject %CV values were 16.23, 15.49 and 15.05, respectively. All the power values were 100%. In this study a single dose of the test formulation met the regulatory requirements to assume bioequivalence, based on the rate and extent of absorption.

Nitazoxanide in the treatment of chronic cutaneous leishmaniasis resistant to traditional sodium stibogluconate

Nitazoxanide in the treatment of chronic cutaneous leishmaniasis resistant to traditional sodium stibogluconate

Treatment of Chronic Hepatitis C Using a 4-week Lead-in With Nitazoxanide Before Peginterferon Plus Nitazoxanide

The primary aim of this study was to further evaluate the efficacy of peginterferon plus nitazoxanide without ribavirin using a 4-week lead-in. The initial treatment of chronic hepatitis C with nitazoxanide used 12 weeks of nitazoxanide monotherapy before combination therapy with peginterferon with or without ribavirin. This open-label pilot study enrolled 44 treatment-naive patients with chronic hepatitis C (40 with genotype 4; 3 with genotype 1; and 1 with genotype 2). The patients received oral nitazoxanide 500 mg twice daily for 4 weeks followed by nitazoxanide plus peginterferon alfa-2a 180 mug weekly for 36 weeks and were then followed for 24 weeks. The results of this study were compared with those from an overlapping historical trial using 12 weeks of nitazoxanide lead-in. A sustained virologic response (SVR) was achieved in 80% of patients, which was similar to the SVR rates in the historical trial, that is, 79% and 61% in patients treated with and without ribavirin, respectively. A rapid virologic response occurred in 59% of patients, which was also similar to the rapid virologic response rates in the historical trial (64% and 54% in patients treated with and without ribavirin, respectively). All 4 patients with genotypes 1 and 2 had an SVR. The nitazoxanide lead-in phase before combination therapy with peginterferon can likely be reduced from 12 weeks to 4 weeks without compromising virologic response rates. In addition, treatment of chronic hepatitis C with peginterferon plus nitazoxanide without ribavirin is promising and requires further study.

Nitazoxanide vs. probiotics for the treatment of acute rotavirus diarrhea in children: a randomized, single-blind, controlled trial in Bolivian children

In previous studies, nitazoxanide has demonstrated a cytoprotective effect against rotavirus, reducing the duration of diarrhea in comparison to placebo. We designed a randomized, single-blind, controlled trial in order to assess the effectiveness of nitazoxanide and probiotics in comparison with a control group. Seventy-five children aged from 28 days to 24 months, with rotavirus diarrhea, were randomly assigned to receive either oral nitazoxanide (15 mg/kg/day) twice a day for three days, a combination of oral probiotics, 1 g twice a day for five days, or only oral or systemic rehydration solutions. The duration of diarrhea and of hospitalization were the primary outcome measures, and daily stool frequency, vomiting, and fever were some of the secondary outcome measures analyzed. The median duration of hospitalization was significantly shorter (p = 0.017) in patients who received nitazoxanide (81 h) and probiotics (72 h) compared to patients who received oral rehydration solution alone (108 h). Similarly, the median duration of diarrhea was significantly reduced (p = 0.009) in children who received nitazoxanide (54 h) and probiotics (48 h) compared to the control group (79 h). Treatment with nitazoxanide and probiotics is effective in the management of children with acute rotavirus diarrhea. Small differences in favor of nitazoxanide were found in comparison with probiotics. Nitazoxanide is an important treatment option for rotavirus diarrhea.