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Antimicrobial Agents and Chemotherapy Apr 2019Albendazole is an effective anthelmintic intensively used for decades. However, profound pharmacokinetic (PK) characterization is missing in children, the population...
Pharmacokinetics of Albendazole, Albendazole Sulfoxide, and Albendazole Sulfone Determined from Plasma, Blood, Dried-Blood Spots, and Mitra Samples of Hookworm-Infected Adolescents.
Albendazole is an effective anthelmintic intensively used for decades. However, profound pharmacokinetic (PK) characterization is missing in children, the population mostly affected by helminth infections. Blood microsampling would facilitate PK studies in pediatric populations but has not been applied to quantify albendazole's disposition. Quantification methods were developed and validated using liquid chromatography-tandem mass spectrometry to analyze albendazole and its metabolites albendazole sulfoxide and albendazole sulfone in wet samples (plasma and blood) and blood microsamples (dried-blood spots [DBS]; Mitra). The use of DBS was limited by a matrix effect and poor recovery, but the extraction efficiency was constant throughout the concentration range. Hookworm-infected adolescents were venous and capillary blood sampled posttreatment with 400 mg albendazole and 25 mg/kg oxantel pamoate. Similar half-life ( = ∼1.5 h), time to reach the maximum concentration ( = ∼2 h), and maximum concentration ( = 12.5 to 26.5 ng/ml) of albendazole were observed in the four matrices. The metabolites reached after ∼4 h with a of ca. 7 to 8 h. A statistically significant difference in albendazole sulfone's as determined by using DBS and wet samples was detected. of albendazole sulfoxide (288 to 380 ng/ml) did not differ among the matrices, but higher of albendazole sulfone were obtained in the two microsampling devices (22 ng/ml) versus the wet matrices (14 ng/ml). In conclusion, time-concentration profiles and PK results of the four matrices were similar, and the direct comparison of the two microsampling devices indicates that Mitra extraction was more robust during validation and can be recommended for future albendazole PK studies.
Topics: Adolescent; Albendazole; Ancylostomatoidea; Animals; Anthelmintics; Chromatography, Liquid; Dried Blood Spot Testing; Hookworm Infections; Humans; Male; Plasma; Pyrantel Pamoate; Tandem Mass Spectrometry
PubMed: 30745388
DOI: 10.1128/AAC.02489-18 -
PLoS Neglected Tropical Diseases Aug 2023There is a lack of systematic evidence for strategies to control loiasis transmission in highly endemic regions. Here we assessed albendazole and ivermectin based... (Randomized Controlled Trial)
Randomized Controlled Trial
Efficacy, safety, and tolerability of albendazole and ivermectin based regimens for the treatment of microfilaraemic loiasis in adult patients in Gabon: A randomized controlled assessor blinded clinical trial.
BACKGROUND
There is a lack of systematic evidence for strategies to control loiasis transmission in highly endemic regions. Here we assessed albendazole and ivermectin based treatment regimens to reduce Loa loa microfilaraemia in Gabon.
METHODS
Eligible adult patients with L. loa microfilaraemia between 5,000 and 50,000 microfilariae/ml were randomized to either a control or one of three intervention groups (1:2:2:2 allocation ratio) consisting of three-week twice daily 400mg oral albendazole followed by 1) no treatment, 2) two further weeks of twice daily 400mg albendazole, or 3) a single dose of ivermectin in this open label randomized assessor blinded controlled clinical trial. The primary outcome was the proportion of participants with L. loa microfilaraemia ≤ 100 mf/ml at Day 168.
RESULTS
In the efficacy-population of 42 patients 0 (0%; control group), 1 (9%; 3-week albendazole), 5 (39%; 5-weeks albendazole) and 2 (22%; 3-week albendazole plus single dose ivermectin) participants met the primary outcome of microfilaraemia below 100/ml at day 168. A 80-90% reduction of microfilaraemia was observed in the active treatment groups.
CONCLUSION
The 5-week regimen of albendazole or a 3-week regimen of albendazole followed by ivermectin were most efficacious to reduce microfilaraemia. All therapeutic regimens were well tolerated and safe.
TRIAL REGISTRATION
Trial registered at the Pan-African Clinical Trials Registry: PACTR201807197019027.
Topics: Humans; Adult; Animals; Albendazole; Ivermectin; Gabon; Loiasis; Clinical Protocols; Fishes
PubMed: 37639396
DOI: 10.1371/journal.pntd.0011584 -
PLoS Neglected Tropical Diseases 2012The currently used anthelmintic drugs, in single oral application, have low efficacy against Trichuris trichiura infection, and hence novel anthelmintic drugs are... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
The currently used anthelmintic drugs, in single oral application, have low efficacy against Trichuris trichiura infection, and hence novel anthelmintic drugs are needed. Nitazoxanide has been suggested as potential drug candidate.
METHODOLOGY
The efficacy and safety of a single oral dose of nitazoxanide (1,000 mg), or albendazole (400 mg), and a nitazoxanide-albendazole combination (1,000 mg-400 mg), with each drug administered separately on two consecutive days, were assessed in a double-blind, randomized, placebo-controlled trial in two schools on Pemba, Tanzania. Cure and egg reduction rates were calculated by per-protocol analysis and by available case analysis. Adverse events were assessed and graded before treatment and four times after treatment.
PRINCIPAL FINDINGS
Complete data for the per-protocol analysis were available from 533 T. trichiura-positive children. Cure rates against T. trichiura were low regardless of the treatment (nitazoxanide-albendazole, 16.0%; albendazole, 14.5%; and nitazoxanide, 6.6%). Egg reduction rates were 54.9% for the nitazoxanide-albendazole combination, 45.6% for single albendazole, and 13.4% for single nitazoxanide. Similar cure and egg reduction rates were calculated using the available case analysis. Children receiving nitazoxanide had significantly more adverse events compared to placebo recipients. Most of the adverse events were mild and had resolved within 24 hours posttreatment.
CONCLUSIONS/SIGNIFICANCE
Nitazoxanide shows no effect on T. trichiura infection. The low efficacy of albendazole against T. trichiura in the current setting characterized by high anthelmintic drug pressure is confirmed. There is a pressing need to develop new anthelmintics against trichuriasis.
Topics: Administration, Oral; Adolescent; Albendazole; Animals; Anthelmintics; Child; Double-Blind Method; Drug Therapy, Combination; Drug-Related Side Effects and Adverse Reactions; Female; Humans; Male; Nitro Compounds; Parasite Egg Count; Placebos; Tanzania; Thiazoles; Treatment Outcome; Trichuriasis; Trichuris
PubMed: 22679525
DOI: 10.1371/journal.pntd.0001685 -
Turkiye Parazitolojii Dergisi Dec 2021In this review, epidemiological features, diagnosis, and treatment processes of cases were discussed. is a spiruroid nematode usually seen in ruminants; it is known to... (Review)
Review
In this review, epidemiological features, diagnosis, and treatment processes of cases were discussed. is a spiruroid nematode usually seen in ruminants; it is known to occasionally infect humans. In humans, reports revealed that it is usually located in the oral cavity and that the most common symptom is the sensation of a moving foreign body in the mouth. Although there is no proven treatment approach yet, it is thought that the most effective treatment is surgery. After surgical treatment, it has been observed that albendazole is administered as the drug therapy in almost all cases. Although the conflict about the benefit of albendazole continues, it is claimed that the drug controls the disease and prevents its recurrence. It has been reported that clinicians sometimes experience difficulties in differential diagnosis due to a lack of knowledge and experience on this rare parasite. A better understanding of the etiopathogenesis of infections will facilitate the diagnosis and treatment of this infection.
Topics: Albendazole; Animals; Diagnosis, Differential; Humans; Nematode Infections; Spirurida Infections; Spiruroidea
PubMed: 34889200
DOI: 10.4274/tpd.galenos.2021.77486 -
Biomedicine & Pharmacotherapy =... Apr 2021Surgery remains the preferred treatment option for hydatid cyst (cystic echinococcosis); however, recent studies have demonstrated that the current protoscolicidal...
BACKGROUND
Surgery remains the preferred treatment option for hydatid cyst (cystic echinococcosis); however, recent studies have demonstrated that the current protoscolicidal agents used during surgery are associated with some adverse side effects such as biliary fibrosis, hepatic necrosis, and cirrhosis. The present study aims to evaluate the in vitro and ex vivo anti-parasitic effects of copper nanoparticles (CuNPs) alone and combined with albendazole on hydatid cyst protoscoleces.
METHODS
CuNPs was green synthesized using C. spinosa extract. Various concentrations of CuNPs (250, 500, and 750 mg/mL) alone and combined with albendazole (ALZ, 200 mg/mL) were exposed to protoscoleces collected from the liver fertile hydatid cysts of infected sheep for 5-60 min in vitro and ex vivo. Next, the eosin exclusion test was applied to determine the viability of protoscoleces. Caspase-3 like activity of CuNPs-treated protoscoleces was then evaluated using the colorimetric protease assay Sigma Kit based on the manufacturer's instructions.
RESULTS
Scanning electron microscopy (SEM) results showed that the particle size of CuNPs was 17 and 41 nm with the maximum peak at the wavelength of 414 nm. The maximum protoscolicidal activity of CuNPs was observed at the concentration of 750 mg/mL in vitro, so that 73.3 % of protoscoleces were killed after 60 min of exposure. Meanwhile, the mortality of protoscoleces was 100 % after 10 min of exposure to 750 mg/mL of CuNPs along with ALZ (200 mg/mL). Nevertheless, the findings proved that CuNPs even in combination with ALZ required a longer time to kill protoscoleces ex vivo. After 48 h of treating protoscoleces, CuNPs in a dose-dependent manner and at doses of 250, 500, and 750 mg/mL induced the caspase enzyme activation by 20.5 %, 32.3 %, and 36.1 %, respectively.
CONCLUSION
The findings of the present investigation showed potent protoscolicidal effects of CuNPs, especially combined with albendazole, which entirely eliminated the parasite after 10-20 min of exposure. The results also showed that although the possible protoscolicidal mechanisms of CuNPs are not clearly understood, the inducing apoptosis through caspases is one of the main protoscolicidal mechanisms of CuNPs. However, supplementary studies, especially in animal models and clinical settings, are needed to approve these results.
Topics: Albendazole; Animals; Anticestodal Agents; Apoptosis; Caspase 3; Copper; Drug Compounding; Echinococcosis, Hepatic; Echinococcus granulosus; Metal Nanoparticles; Nanotechnology; Protozoan Proteins; Sheep, Domestic
PubMed: 33450495
DOI: 10.1016/j.biopha.2021.111257 -
The American Journal of Tropical... Sep 2017
Topics: Adult; Albendazole; Animals; Anthelmintics; Echinococcosis, Pulmonary; Echinococcus granulosus; Female; Humans; Pneumonectomy; Radiography, Thoracic; Tomography, X-Ray Computed
PubMed: 28990910
DOI: 10.4269/ajtmh.17-0298 -
Genetics Jul 2022Parasitic nematodes are major human and agricultural pests, and benzimidazoles are amongst the most important broad-spectrum anthelmintic drug class used for their...
Parasitic nematodes are major human and agricultural pests, and benzimidazoles are amongst the most important broad-spectrum anthelmintic drug class used for their control. Benzimidazole resistance is now widespread in many species of parasitic nematodes in livestock globally and an emerging concern for the sustainable control of human soil-transmitted helminths. β-tubulin is the major benzimidazole target, although other genes may influence resistance. Among the 6 Caenorhabditis elegans β-tubulin genes, loss of ben-1 causes resistance without other apparent defects. Here, we explored the genetics of C. elegans β-tubulin genes in relation to the response to the benzimidazole derivative albendazole. The most highly expressed β-tubulin isotypes, encoded by tbb-1 and tbb-2, were known to be redundant with each other for viability, and their products are predicted not to bind benzimidazoles. We found that tbb-2 mutants, and to a lesser extent tbb-1 mutants, were hypersensitive to albendazole. The double mutant tbb-2 ben-1 is uncoordinated and short, resembling the wild type exposed to albendazole, but the tbb-1 ben-1 double mutant did not show the same phenotypes. These results suggest that tbb-2 is a modifier of albendazole sensitivity. To better understand how BEN-1 mutates to cause benzimidazole resistance, we isolated mutants resistant to albendazole and found that 15 of 16 mutations occurred in the ben-1 coding region. Mutations ranged from likely nulls to hypomorphs, and several corresponded to residues that cause resistance in other organisms. Null alleles of ben-1 are albendazole-resistant and BEN-1 shows high sequence identity with tubulins from other organisms, suggesting that many amino acid changes could cause resistance. However, our results suggest that missense mutations conferring resistance are not evenly distributed across all possible conserved sites. Independent of their roles in benzimidazole resistance, tbb-1 and tbb-2 may have specialized functions as null mutants of tbb-1 or tbb-2 were cold or heat sensitive, respectively.
Topics: Albendazole; Animals; Anthelmintics; Benzimidazoles; Caenorhabditis elegans; Drug Resistance; Humans; Microtubules; Tubulin; Tubulin Modulators
PubMed: 35731216
DOI: 10.1093/genetics/iyac093 -
Memorias Do Instituto Oswaldo Cruz 2020It was previously demonstrated that CMC-20, a nitazoxanide and N-methyl-1H-benzimidazole hybrid molecule, had higher in vitro activity against Giardia intestinalis WB...
Characterisation of the in vitro activity of a Nitazoxanide-N-methyl-1H-benzimidazole hybrid molecule against albendazole and nitazoxanide susceptible and resistant strains of Giardia intestinalis and its in vivo giardicidal activity.
BACKGROUND
It was previously demonstrated that CMC-20, a nitazoxanide and N-methyl-1H-benzimidazole hybrid molecule, had higher in vitro activity against Giardia intestinalis WB strain than metronidazole and albendazole and similar to nitazoxanide.
OBJETIVES
To evaluate the in vitro activity of CMC-20 against G. intestinalis strains with different susceptibility/resistance to albendazole and nitazoxanide and evaluate its effect on the distribution of parasite cytoskeletal proteins and its in vivo giardicidal activity.
METHODS
CMC-20 activity was tested against two isolates from patients with chronic and acute giardiasis, an experimentally induced albendazole resistant strain and a nitazoxanide resistant clinical isolate. CMC-20 effect on the distribution of parasite cytoskeletal proteins was analysed by indirect immunofluorescence and its activity was evaluated in a murine model of giardiasis.
FINDINGS CMC-20
showed broad activity against susceptible and resistant strains to albendazole and nitaxozanide. It affected the parasite microtubule reservoir and triggered the parasite encystation. In this process, alpha-7.2 giardin co-localised with CWP-1 protein. CMC-20 reduced the infection time and cyst load in feces of G. muris infected mice similar to albendazole.
MAIN CONCLUSIONS
The in vitro and in vivo giardicidal activity of CMC-20 suggests its potential use in the treatment of giardiasis.
Topics: Albendazole; Animals; Antiprotozoal Agents; Cytoskeletal Proteins; Fluorescent Antibody Technique, Indirect; Giardia lamblia; Humans; Mice; Nitro Compounds; Parasitic Sensitivity Tests; Thiazoles; Time Factors
PubMed: 32049098
DOI: 10.1590/0074-02760190348 -
World Journal of Gastroenterology Jan 2015A review was carried out in Medline, LILACS and the Cochrane Library. Our database search strategy included the following terms: "hydatid cyst", "liver", "management",... (Review)
Review
UNLABELLED
A review was carried out in Medline, LILACS and the Cochrane Library. Our database search strategy included the following terms: "hydatid cyst", "liver", "management", "meta-analysis" and "randomized controlled trial". No language limits were used in the literature search. The latest electronic search date was the 7(th) of January 2014.
INCLUSION AND EXCLUSION CRITERIA
all relevant studies on the assessment of therapeutic methods for hydatid cysts of the liver were considered for analysis. Information from editorials, letters to publishers, low quality review articles and studies done on animals were excluded from analysis. Additionally, well-structured abstracts from relevant articles were selected and accepted for analysis. Standardized forms were designed for data extraction; two investigators entered the data on patient demographics, methodology, recurrence of HC, mean cyst size and number of cysts per group. Four hundred and fourteen articles were identified using the previously described search strategy. After applying the inclusion and exclusion criteria detailed above, 57 articles were selected for final analysis: one meta-analysis, 9 randomized clinical trials, 5 non-randomized comparative prospective studies, 7 non-comparative prospective studies, and 34 retrospective studies (12 comparative and 22 non-comparative). Our results indicate that antihelminthic treatment alone is not the ideal treatment for liver hydatid cysts. More studies in the literature support the effectiveness of radical treatment compared with conservative treatment. Conservative surgery with omentoplasty is effective in preventing postoperative complications. A laparoscopic approach is safe in some situations. Percutaneous drainage with albendazole therapy is a safe and effective alternative treatment for hydatid cysts of the liver. Radical surgery with pre- and post-operative administration of albendazole is the best treatment option for liver hydatid cysts due to low recurrence and complication rates.
Topics: Albendazole; Antiparasitic Agents; Combined Modality Therapy; Drainage; Echinococcosis, Hepatic; Humans; Laparoscopy; Recurrence; Treatment Outcome
PubMed: 25574085
DOI: 10.3748/wjg.v21.i1.124 -
Comparative Medicine Oct 2023( ), the causative agent of the most commonly reported disease of zebrafish, is a microsporidian parasite that confounds research by inducing behavioral and...
( ), the causative agent of the most commonly reported disease of zebrafish, is a microsporidian parasite that confounds research by inducing behavioral and physiologic changes in zebrafish. Although a treatment for has not been documented in zebrafish, albendazole (ALB) and fumagillin (FUM) have been used to treat microsporidian infections of other fish species. To investigate the efficacy of oral ALB and FUM in the treatment of we performed a pilot study that demonstrated the safety and palatability of novel gel-based diets containing FUM or ALB in adult AB zebrafish. In a subsequent study, approximately 250 adult AB zebrafish (previously infected with ) were treated with these medicated diets for 4 wk. At 4 different time points (weeks 0, 5, 10, and 16 of the study), fish were euthanized and whole-body qPCR was performed to assess prevalence across treatment and control groups. There was no statistically significant association between treatment group and prevalence at any time point, although potential biologically relevant reductions in prevalence occurred in the combination therapy group at weeks 5 and 16 and in the ALB group at week 5. Based on high-performance liquid chromatography analyses, the medicated diets contained less ALB and more FUM than expected, highlighting the importance of validating medicated feed concentrations to ensure safety, efficacy, and consistency. While remains challenging to eradicate and control, results of this study warrant further investigation into the utility of ALB and FUM as potential treatments for this pathogen.
Topics: Animals; Zebrafish; Albendazole; Pilot Projects; Microsporidia
PubMed: 38087410
DOI: 10.30802/AALAS-CM-23-000035