Oxfendazole

Oxfendazole

Efficacy of ivermectin and oxfendazole against Taenia solium cysticercosis and other parasitoses in naturally infected pigs.[Pubmed:23806569]

Acta Trop. 2013 Oct;128(1):48-53.

Smallholder semi-confined pig production is a fast growing practice in sub-Saharan Africa with an unfortunate outcome of high prevalence of Taenia solium cysticercosis and other parasitoses. The widely used anthelmintic for control of endo and ecto-parasites in pigs in the area is ivermectin at a recommended dose of 0.3mg/kg. This study was conducted to evaluate the efficacy and safety in pigs after subcutaneous injection of ivermectin (IVM, 0.3mg/kg) and orally administration of Oxfendazole (OFZ, 30mg/kg) in treatment of porcine cysticercosis and other parasitoses in naturally infected pigs. A total of 61 pigs with T. solium cysticercosis (38 males and 23 females) as identified by tongue palpation with age ranging from 3 to 24 months were recruited. The pigs were stratified based on sex, age and number of cysts on the tongue and randomly allocated to IVM, OFZ and control groups. Three days before treatment and two weeks after treatment faecal samples and skin scrapings were taken to establish the burden of endo- and ectoparasites, respectively and the effect of the treatment. No adverse effect was observed in any of the treatment groups throughout the study period. Half of the pigs from each group were slaughtered at week four and the remaining half at week twelve post treatment. The IVM treatment group had no significant effect (p=0.224) on T. solium cysts viability in comparison to the control group. Significant effect on cysts viability was observed in the OFZ treated group (p<0.001) compared to IVM and control groups in all muscle tissues. Regarding to brain cysts, neither of the drugs was efficacious. Ivermectin and OFZ treatments significantly reduced (p<0.001) the faecal egg count of Ascaris suum, strongyles and Trichuris suis two weeks after treatment. At slaughter, Oesophagostomum dentatum, Ascarops strongylina and Physocephalus sexalatus were recovered from pigs in the IVM treated and in the control groups. Ivermectin was 100% effective in control of Sarcoptes scabiei. In conclusion, IVM at a single dose of 0.3mg/kg was efficacious against ectoparasites but did not effectively cure pigs from T. solium cysticercosis or nematodes. Oxfendazole, on the other hand, killed all nematodes and muscle cysts, but did not have any effect on ectoparasites. A combination of the two drugs would be a most useful treatment option for control of pig parasitoses in sub-Saharan Africa.

Oxfendazole flukicidal activity in pigs.[Pubmed:24713198]

Acta Trop. 2014 Aug;136:10-3.

Although Oxfendazole (OFZ) is a well know broad-spectrum benzimidazole anthelmintic, the assessment of its potential trematodicidal activity remains unexplored. OFZ administration at single high doses has been recommended to control Taenia solium cysticercus in pigs. The current study investigated the flukicidal activity obtained after a single high (30mg/kg) oral dose of OFZ in pigs harbouring a natural Fasciola hepatica infection. Sixteen (16) local ecotype pigs were randomly allocated into two (2) experimental groups of 8 animals each named as follow: Untreated control and OFZ treated, in which animals received OFZ (Synanthic((R)), Merial Ltd., 9.06% suspension) orally at 30mg/kg. At seven (7) days post-treatment, all the animals were sacrificed and direct adult liver fluke counts were performed following the WAAVP guidelines. None of the animals involved in this experiment showed any adverse event during the study. OFZ treatment as a single 30mg/kg oral dose showed a 100% efficacy against F. hepatica. In conclusion, the trial described here demonstrated an excellent OFZ activity against F. hepatica in naturally infected pigs, after its administration at a single oral dose of 30mg/kg.

Preclinical studies on the pharmacokinetics, safety, and toxicology of oxfendazole: toward first in human studies.[Pubmed:25701764]

Int J Toxicol. 2015 Mar-Apr;34(2):129-37.

A 2-week study in rats identified target organs of Oxfendazole toxicity to be bone marrow, epididymis, liver, spleen, testis, and thymus. Female rats had greater Oxfendazole exposure and exhibited toxicities at lower doses than did males. Decreased white blood cell levels, a class effect of benzimidazole anthelmintics, returned to normal during the recovery period. The no observed adverse effect level was determined to be >5 but <25 mg/kg/d and the maximum tolerated dose 100 mg/kg/d. The highest dose, 200 mg/kg/d, resulted in significant toxicity and mortality, leading to euthanization of the main study animals in this group after 7 days. Oxfendazole did not exhibit genetic toxicology signals in standard Ames bacterial, mouse lymphoma, or rat micronucleus assays nor did it provoke safety concerns when evaluated for behavioral effects in rats or cardiovascular safety effects in dogs. These results support the transition of Oxfendazole to First in Human safety studies preliminary to its evaluation in human helminth diseases.

Simultaneous determination of praziquantel, pyrantel embonate, febantel and its active metabolites, oxfendazole and fenbendazole, in dog plasma by liquid chromatography/mass spectrometry.[Pubmed:26104502]

Biomed Chromatogr. 2015 Dec;29(12):1859-65.

A liquid chromatography-electrospray-mass spectrometry method (LC/MS) has been developed and validated for determination of praziquantel (PZQ), pyrantel (PYR), febantel (FBT), and the active metabolites fenbendazole (FEN) and Oxfendazole (OXF), in dog plasma, using mebendazole as internal standard (IS). The method consists of solid-phase extractions on Strata-X polymeric cartridges. Chromatographic separation was carried out on a Phenomenex Gemini C6 -Phenyl column using binary gradient elution containing methanol and 50 mm ammonium-formate (pH 3). The method was linear (r(2) >/= 0.990) over concentration ranges of 3-250 ng/mL for PYR andFEB, 5-250 ng/mL for OXF and FEN, and 24-1000 ng/mL for PZQ. The mean precisions were 1.3-10.6% (within-run) and 2.5-9.1% (between-run), and mean accuracies were 90.7-109.4% (within-run) and 91.6-108.2% (between-run). The relative standard deviations (RSD) were <9.1%. The mean recoveries of five targeted compounds from dog plasma ranged from 77 to 94%.The new LC/MS method described herein was fully validated and successfully applied to the bioequivalence studies of different anthelmintic formulations such as tablets containing PZQ, PYR embonate and FBT in dogs after oral administration.