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Microbiology Spectrum Aug 2022Infections caused by parasitic helminths have enormous health, social, and economic impacts worldwide. The treatment and control of these diseases have been dependent on...
Infections caused by parasitic helminths have enormous health, social, and economic impacts worldwide. The treatment and control of these diseases have been dependent on a limited set of drugs, many of which have become less effective, necessitating the search for novel anthelmintic agents. In this study, a simplified compound, -(4-methoxyphenyl)pentanamide (N4MP), based on the structure of the most widely used anthelmintic (albendazole), was chemically prepared using 4-anisidine and pentanoic acid. -(4-Methoxyphenyl)pentanamide was evaluated against the nematode Toxocara canis, an ascarid roundworm of animals that can infect humans. Similar to albendazole, bioassays showed that -(4-methoxyphenyl)pentanamide affected the viability of parasites in a time- and concentration-dependent manner. Interestingly, -(4-methoxyphenyl)pentanamide showed a profile of lower cytotoxicity to human and animal cell lines than albendazole. Pharmacokinetic, drug-likeness, and medicinal chemistry friendliness studies demonstrated an excellent drug-likeness profile for -(4-methoxyphenyl)pentanamide as well as an adherence to major pharmaceutical companies' filters. Collectively, the results of this study demonstrate that the molecular simplification of albendazole to give -(4-methoxyphenyl)pentanamide may be an important pipeline in the discovery of novel anthelmintic agents. Infections caused by parasitic helminths have enormous health, social, and economic impacts worldwide. The treatment and control of these diseases have been dependent on a limited set of drugs, many of which have become less effective, necessitating the search for novel anthelmintic agents. Considering this scenario, the present study reports the preparation of -(4-methoxyphenyl)pentanamide (N4MP), a simplified molecule based on the structure of the most widely used anthelmintic (albendazole). N4MP was evaluated against the nematode Toxocara canis, a common ascarid roundworm of domestic animals that can infect humans. Similar to albendazole, bioassays showed that N4MP affected the viability of parasites in a time- and concentration-dependent manner but displayed a profile of lower cytotoxicity to human and animal cell lines than albendazole. Therefore, this study demonstrates that the molecular simplification of albendazole to give N4MP may be an important pipeline in the discovery of novel anthelmintic agents.
Topics: Albendazole; Animals; Anthelmintics; Humans; Toxocara canis; Toxocariasis
PubMed: 35900089
DOI: 10.1128/spectrum.01807-22 -
Transactions of the Royal Society of... 1990
Topics: Albendazole; Brain Diseases; Cysticercosis; Humans
PubMed: 2345923
DOI: 10.1016/0035-9203(90)90421-a -
Parasitology Jan 2022Alveolar echinococcosis (AE) is a severe disease caused by Echinococcus multilocularis. Its chemotherapeutic treatment is based on benzimidazoles, which are rarely...
Alveolar echinococcosis (AE) is a severe disease caused by Echinococcus multilocularis. Its chemotherapeutic treatment is based on benzimidazoles, which are rarely curative and cause several adverse effects. Therefore, it is necessary to develop alternative and safer chemotherapeutic strategies against AE. It has previously been shown that metformin (Met) exhibits considerable in vivo activity on an early-infection model of AE when administered at 50 mg kg−1 day−1 for 8 weeks. Here, the challenge is heightened by a 2-fold increase in parasite inoculum or by starting the treatment 6 weeks post-infection. In both cases, only the combination of Met (100 mg kg−1 day−1) together with a sub-optimal dose of albendazole (ABZ) (5 mg kg−1 day−1) led to a significant reduction in parasite weight compared to the untreated group. Coincidentally, drug combination showed the highest level of damage in E. multilocularis metacestodes. Likewise, Met alone or combined with ABZ led to a decrease in parasite glucose availability, which was evidenced as a lower intracystic glucose concentration. Therefore, the results demonstrate that combination therapy with Met and ABZ offers an alternative to improve the efficacy and reduce the toxicity of the high-dose ABZ monotherapy currently employed.
Topics: Albendazole; Animals; Anthelmintics; Echinococcosis; Echinococcus multilocularis; Metformin
PubMed: 35184788
DOI: 10.1017/S0031182021001633 -
Thorax Aug 1991Ten patients with pulmonary hydatid disease diagnosed on the basis of a chest radiograph and a positive response to the indirect haemagglutination test for hydatid...
Ten patients with pulmonary hydatid disease diagnosed on the basis of a chest radiograph and a positive response to the indirect haemagglutination test for hydatid disease were treated with albendazole 10 mg/kg/day for eight weeks. None of the 10 patients showed any radiological or serological improvement with this treatment regimen. Albendazole in these doses appears to have little role in the treatment of pulmonary hydatid disease.
Topics: Adolescent; Adult; Albendazole; Drug Administration Schedule; Echinococcosis, Pulmonary; Humans; Patient Compliance
PubMed: 1926033
DOI: 10.1136/thx.46.8.599 -
Veterinary Parasitology, Regional... Aug 2019Albendazole is a benzimidazole derivative with anthelmintic activity. It is the treatment of choice for fasciolosis. The use of albendazole in South American camelids is...
Albendazole is a benzimidazole derivative with anthelmintic activity. It is the treatment of choice for fasciolosis. The use of albendazole in South American camelids is common, however, there are no studies about the pharmacokinetics and pharmacodynamics of albendazole in alpacas and llamas. In the present study, a case of fiber loss (alopecia) in alpacas is described because of the suspected use of a high dose of albendazole. In a fasciolosis control program of an alpaca ranch located in the district of Nuñoa in Puno, Peru, 2184 alpacas were oral treated with albendazole (35-40 mg/kg). After 2 weeks of treatment the alpacas began to show loss of fiber in the abdomen, flanks and neck. The alpacas showed no other sign of disease. The alpacas recovered their fiber after 6 months. We suggest studies are needed to determine the safe dose of albendazole in alpacas.
Topics: Administration, Oral; Albendazole; Alopecia; Animals; Anthelmintics; Camelids, New World; Fascioliasis; Peru
PubMed: 31303236
DOI: 10.1016/j.vprsr.2019.100297 -
Current Opinion in Infectious Diseases Oct 2023Cystic echinococcosis (CE) has a wide world distribution causing important morbidity. Osseous involvement is present in less than 4% of the CE cases. Its diagnosis and... (Review)
Review
PURPOSE OF REVIEW
Cystic echinococcosis (CE) has a wide world distribution causing important morbidity. Osseous involvement is present in less than 4% of the CE cases. Its diagnosis and therapeutic management is full of challenges and low grade of evidence.
RECENT FINDINGS
The study summarizes literature evidence on the management of osseous CE with particular emphasis on new data regarding diagnosis and treatment.
SUMMARY
Clinical presentation of osseous CE depends on the skeletal area affected. Diagnosis is mostly based on radiological findings and serology. Recent advances with qPCR on osseous tissue samples seem to be a good option for diagnosis confirmation. Complete resection of the cystic lesion is the only curative option, but it is usually not possible performing palliative surgery and prolonged albendazole intake in most cases. Radiotherapy could be an option, but experience to date is only based on clinical cases.
Topics: Humans; Echinococcosis; Albendazole
PubMed: 37593962
DOI: 10.1097/QCO.0000000000000951 -
Parasitology Nov 2020In this study, we evaluated the efficacy, expressed as a mean weight decrease of the whole echinococcal cyst mass, of novel benzimidazole salt formulations in a murine...
In this study, we evaluated the efficacy, expressed as a mean weight decrease of the whole echinococcal cyst mass, of novel benzimidazole salt formulations in a murine Echinococcus granulosus infection model. BALB/c mice were intraperitoneally infected with protoscoleces of E. granulosus (genotype G1). At 9 months post-infection, treatment with albendazole (ABZ), ricobendazole (RBZ) salt formulations, and RBZ enantiomer salts (R)-(+)-RBZ-Na and (S)-(-)-RBZ-Na formulations were initiated. Drugs were orally applied by gavage at 10 mg kg-1 body weight per day during 30 days. Experimental treatments with benzimidazole sodium salts resulted in a significant reduction of the weight of cysts compared to conventional ABZ treatment, except for the (S)-(-)-RBZ-Na enantiomer formulation. Scanning electron microscopy and histological inspection revealed that treatments impacted not only the structural integrity of the parasite tissue in the germinal layer, but also induced alterations in the laminated layer. Overall, these results demonstrate the improved efficacy of benzimidazole salt formulations compared to conventional ABZ treatment in experimental murine cystic echinococcosis.
Topics: Albendazole; Animals; Anticestodal Agents; Echinococcosis; Echinococcus granulosus; Female; Mice; Mice, Inbred BALB C; Salts
PubMed: 32729453
DOI: 10.1017/S0031182020001225 -
Journal of Veterinary Pharmacology and... Oct 2018This work characterized the egg residual concentrations of albendazole (ABZ) and its sulphoxide (ABZSO) and sulphone (ABZSO ) metabolites and evaluated their effect on...
This work characterized the egg residual concentrations of albendazole (ABZ) and its sulphoxide (ABZSO) and sulphone (ABZSO ) metabolites and evaluated their effect on egg fertility and hatchability after ABZ treatments to laying hens. Seventy hens were allocated in groups: Group-1 was the control without treatment; Group-2 received a single ABZ oral dose (10 mg/kg); Group-3, -4 and -5 were treated with ABZ in medicated feed over 7 days at 10, 40, or 80 mg kg day , respectively. Eggs were analyzed to determine the ABZ/metabolite level by HPLC or subjected to incubation to evaluate the fertility and hatchability. Only ABZSO and ABZSO metabolites were quantified in egg after ABZ single oral administration with maximum concentrations of 0.47 ± 0.08 and 0.30 ± 0.07 μg/ml, respectively. ABZ and its metabolites were found in eggs after 7-day ABZ treatments. The egg residue exposure estimated as AUCs (areas under the concentration vs. time curve) were 100.5 (ABZ), 56.3 (ABZSO) and 141.3 μg hr g (ABZSO ). ABZ administration did not affect the egg fertility at any dosages. Egg hatchability was not affected by ABZ treatment at 10 mg/kg in medicated feed, but it decreased when the dose was 4-8 times higher. These results should be considered when ABZ is used for deworming laying hens.
Topics: Administration, Oral; Albendazole; Animals; Anthelmintics; Chick Embryo; Chickens; Chromatography, High Pressure Liquid; Drug Residues; Female; Fertility; Ovum
PubMed: 29894001
DOI: 10.1111/jvp.12675 -
The Journal of Infectious Diseases Jul 1993To assess the filaricidal activity and clinical safety of albendazole in human loiasis, a double-blind, placebo-controlled study was conducted in an endemic area in... (Clinical Trial)
Clinical Trial Randomized Controlled Trial
To assess the filaricidal activity and clinical safety of albendazole in human loiasis, a double-blind, placebo-controlled study was conducted in an endemic area in Benin, Africa. Twenty-three men with microfilaremia (100-30,000/mL) were randomly assigned to receive albendazole (200 mg; n = 11) or placebo (n = 12) twice daily for 21 days; 1 patient from each group withdrew from the study. There were no clinical adverse effects and no observed hepatotoxicity, renal toxicity, or hematologic abnormalities attributable to the drug. In the albendazole group, microfilarial levels began to decrease at day 14 after treatment and by 6 months had fallen to a geometric mean of 20% of pretreatment levels (vs. 84.8% in the placebo group). Blood eosinophil levels and anti-filarial IgG and IgG4 also fell significantly in response to albendazole. Taken together, these data suggest that albendazole has a primary (possibly embryotoxic) effect on the adult parasite, resulting in a slow decrease in microfilaremia.
Topics: Adolescent; Adult; Africa, Western; Aged; Albendazole; Double-Blind Method; Female; Humans; Loiasis; Male; Middle Aged
PubMed: 8515109
DOI: 10.1093/infdis/168.1.202 -
AAPS PharmSciTech Apr 2018Albendazole, an effective broad-spectrum anthelmintic agent, showed unpredictable therapeutic response caused by poor water solubility and slow dissolution rate. Then,...
Albendazole, an effective broad-spectrum anthelmintic agent, showed unpredictable therapeutic response caused by poor water solubility and slow dissolution rate. Then, novel binary and multicomponent supramolecular systems of two different solid forms of albendazole (I and II) with maltodextrin alone or with glutamic acid were studied as an alternative to improve the oral bioavailability of albendazole. The interactions and effects on the properties of albendazole were studied in solution and solid state. The solid systems were characterized using Raman and Fourier transform-infrared spectroscopy, thermal analysis, powder X-ray diffraction, and scanning electron microscopy. The solubility measurements, performed in aqueous and simulated gastric fluid, showed that albendazole (form II) was the most soluble form, while its supramolecular systems showed the highest solubility in simulated gastric fluid. On the other hand, the dissolution profiles of binary and multicomponent systems in simulated gastric fluid displayed pronounced increments of the dissolved drug and a faster dissolution rate compared to those of free albendazole forms. Thus, these supramolecular structures constitute an interesting alternative to improve the physicochemical properties of albendazole, with potential application for the preparation of pharmaceutical oral formulations.
Topics: Albendazole; Anthelmintics; Gastric Juice; Glutamic Acid; Polysaccharides; Solubility
PubMed: 29464593
DOI: 10.1208/s12249-018-0952-0