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      A systematic review of fluralaner as a treatment for ectoparasitic infections in mammalian species

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      PeerJ
      PeerJ Inc.
      Bravecto®, Exzolt, Mammal, Efficacy, Ectoparasite, Treatment, Side effect, Pharmacokinetic, Safety, Environment

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          Abstract

          Fluralaner (Bravecto™) is a novel isoxazoline ectoparasiticide used for controlling ectoparasites of domestic mammals and is increasingly being used on wildlife. The aim of this systematic review was to evaluate the efficacy, pharmacokinetics, and safety of fluralaner on mammals given its increasing use. The search was performed in GoogleScholar and the SciFinder databases using the terms ‘fluralaner’ and ‘Bravecto™’, and was concluded on 30th August, 2024. A total of 250 references were initially saved and reduced to 121 peer-reviewed journal articles using PRISMA guidelines, based on the removal of duplicates, those published in low quality journals (ranked less than Q2), and limiting publications to clinical trials. Articles were then categorised and ranked using the level of evidence, Cochrane ‘risk of bias’ assessment tool, methodological quality, and study size. Overall, the efficacy of fluralaner has been assessed on 14 mammalian species, and pharmacokinetic investigations conducted on 15. Fluralaner was mostly effective at treating some ectoparasites on captive individuals when there was little chance of re-infection; however, it did not prevent bites from blood-sucking ectoparasites and could not prevent blood-borne pathogen transfer to host animals. Very few studies have investigated the pharmacokinetics of fluralaner, and hence were difficult to compare; however, wombats differed greatly from their eutherian counterparts in their C max and t½ values and require further investigation. Overall, fluralaner was deemed moderately safe; however, most studies were classified as fair in terms of quality and most studies were based on small or very small sample numbers. Nineteen studies reported side effects, one of which included signs of severe neurological toxicity, with most of the articles not reporting on safety either positively or negatively. Concerns were raised regarding the extended time fluralaner was detected in faeces and subsequently environmental contamination is a concern. No longer-term impacts of the use of fluralaner have been investigated, and wider implications of the use of this ectoparasiticide have not yet been assessed.

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          The novel isoxazoline ectoparasiticide fluralaner: selective inhibition of arthropod γ-aminobutyric acid- and L-glutamate-gated chloride channels and insecticidal/acaricidal activity.

          Isoxazolines are a novel class of parasiticides that are potent inhibitors of γ-aminobutyric acid (GABA)-gated chloride channels (GABACls) and L-glutamate-gated chloride channels (GluCls). In this study, the effects of the isoxazoline drug fluralaner on insect and acarid GABACl (RDL) and GluCl and its parasiticidal potency were investigated. We report the identification and cDNA cloning of Rhipicephalus (R.) microplus RDL and GluCl genes, and their functional expression in Xenopus laevis oocytes. The generation of six clonal HEK293 cell lines expressing Rhipicephalus microplus RDL and GluCl, Ctenocephalides felis RDL-A285 and RDL-S285, as well as Drosophila melanogaster RDLCl-A302 and RDL-S302, combined with the development of a membrane potential fluorescence dye assay allowed the comparison of ion channel inhibition by fluralaner with that of established insecticides addressing RDL and GluCl as targets. In these assays fluralaner was several orders of magnitude more potent than picrotoxinin and dieldrin, and performed 5-236 fold better than fipronil on the arthropod RDLs, while a rat GABACl remained unaffected. Comparative studies showed that R. microplus RDL is 52-fold more sensitive than R. microplus GluCl to fluralaner inhibition, confirming that the GABA-gated chloride channel is the primary target of this new parasiticide. In agreement with the superior RDL on-target activity, fluralaner outperformed dieldrin and fipronil in insecticidal screens on cat fleas (Ctenocephalides felis), yellow fever mosquito larvae (Aedes aegypti) and sheep blowfly larvae (Lucilia cuprina), as well as in acaricidal screens on cattle tick (R. microplus) adult females, brown dog tick (Rhipicephalus sanguineus) adult females and Ornithodoros moubata nymphs. These findings highlight the potential of fluralaner as a novel ectoparasiticide. Copyright © 2014 Elsevier Ltd. All rights reserved.
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            A randomized, blinded, controlled and multi-centered field study comparing the efficacy and safety of Bravecto™ (fluralaner) against Frontline™ (fipronil) in flea- and tick-infested dogs

            Background Fluralaner, a new molecular entity of the isoxazoline class, has potent insecticidal and acaricidal activity and can be safely administered orally to dogs. Methods A randomized, investigator-blinded, multi-centered field study compared the flea- and tick-control efficacy for dogs over a 12-week period with either a single oral dose of Bravecto™ (fluralaner) formulated as a chewable tablet or with three sequential topical Frontline™ (fipronil) treatments. Individual dogs were the experimental unit for ticks and households were the experimental unit for fleas. A total of 108 tick-infested dogs were treated with Bravecto™ (fluralaner) and 54 tick-infested dogs were treated with Frontline™ (fipronil). Dogs in 115 flea-infested households received Bravecto™ (fluralaner) and dogs in 61 flea-infested households received Frontline™ (fipronil). Flea and tick counts were conducted on all dogs at weeks 2, 4, 8, and 12 following initial treatment and efficacy was calculated as the mean percent reduction in tick or flea count at each time point compared with the mean pretreatment initiation count for each treatment group. Additionally, the percentages of tick-free and flea-free households were determined. Results At weeks 2, 4, 8, and 12, Bravecto™ (fluralaner) flea-control efficacy in treated households was 99.2%, 99.8%, 99.8%, and 99.9% respectively, while Frontline™ (fipronil) efficacy was 94.1%, 93.0%, 96.0%, and 97.3%, respectively. Bravecto™ (fluralaner) tick-control efficacy on treated dogs at weeks 2, 4, 8, and 12 was 99.9%, 99.9%, 99.7%, and 100%, respectively, and Frontline™ (fipronil) tick efficacy was 97.6%, 93.8%, 100%, and 100%, respectively. Of dogs showing clinical flea allergy dermatitis (FAD) signs at the study start, 85.7% in the Bravecto™ (fluralaner)-treated group and 55.6% in the Frontline™ (fipronil)-treated group were evaluated at each time point as showing no clinical signs of FAD until study completion. Conclusions Bravecto™ (fluralaner) administered once orally to dogs in a chewable tablet was highly effective for 12 weeks against fleas and ticks on privately-owned dogs and was significantly non-inferior (ticks) and superior (fleas) in comparison with topical Frontline™ (fipronil) administered 3 times sequentially.
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              Sarcoptic mange in wildlife

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                Author and article information

                Contributors
                Journal
                PeerJ
                PeerJ
                PeerJ
                PeerJ
                PeerJ Inc. (San Diego, USA )
                2167-8359
                12 March 2025
                2025
                : 13
                : e18882
                Affiliations
                [-1]School of Science, Western Sydney University , Penrith, NSW, Australia
                Author information
                http://orcid.org/0000-0002-2754-7757
                Article
                18882
                10.7717/peerj.18882
                11910153
                40093406
                bde4b7ad-f1f1-4c01-8aeb-aa5ef627e4a0
                © 2025 Jiang and Old

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, reproduction and adaptation in any medium and for any purpose provided that it is properly attributed. For attribution, the original author(s), title, publication source (PeerJ) and either DOI or URL of the article must be cited.

                History
                : 30 September 2024
                : 28 December 2024
                Funding
                The authors received no funding for this work.
                Categories
                Veterinary Medicine
                Zoology

                bravecto®,exzolt,mammal,efficacy,ectoparasite,treatment,side effect,pharmacokinetic,safety,environment

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