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      Assessment of afoxolaner efficacy against Otodectes cynotis infestations of dogs

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          Abstract

          Background

          The efficacy of a single 2.5 mg/kg dose of afoxolaner (NexGard®, Merial) against induced Otodectes cynotis infestations was assessed in eight afoxolaner-treated dogs, compared to eight untreated dogs.

          Methods

          After O. cynotis infestations were established and confirmed by otoscopic assessments in 16 dogs, all of the dogs were included in the study and allocated to two separate treatment groups. The first group of eight ear mite-infested dogs remained untreated, while afoxolaner was administered orally to the second group of dogs at the minimum recommended dose once on Day 0. Otoscopic assessments performed on all dogs (Days -7, -2, 14 and 28) confirmed the presence or absence of live mites throughout the study. No serious adverse events were recorded throughout the study, and no adverse events were likely related to the administration of NexGard.

          Results

          By Day 28, seven out of eight untreated dogs were still infested with ear mites, while only two out of eight afoxolaner-treated dogs were infested, with one and four ear mites, respectively. On Day 28, the reductions of mite counts in the afoxolaner-treated group versus those of the control dogs were 98.5% based on geometric means, and 99.4% based on arithmetic means. Significantly fewer ( P < 0.05) live mites were present in the afoxolaner-treated group than the untreated group on Day 28.

          Conclusion

          The results of this study demonstrated that a single oral administration of afoxolaner at the minimum recommended dose is highly effective (>98%) in treating dogs with induced O. cynotis infestations.

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          Most cited references12

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          Discovery and mode of action of afoxolaner, a new isoxazoline parasiticide for dogs.

          Afoxolaner is an isoxazoline compound characterized by a good safety profile and extended effectiveness against fleas and ticks on dogs following a single oral administration. In vitro membrane feeding assay data and in vivo pharmacokinetic studies in dogs established an afoxolaner blood concentration of 0.1-0.2 μg/ml to be effective against both fleas (Ctenocephalides felis) and ticks (Dermacentor variabilis). Pharmacokinetic profiles in dogs following a 2.5mg/kg oral dosage demonstrated uniform and predictable afoxolaner plasma concentrations above threshold levels required for efficacy for more than one month. Dose ranging and a 5-month multi-dose experimental study in dogs, established that the 2.5mg/kg oral dosage was highly effective against fleas and ticks, and produced predictable and reproducible pharmacokinetics following repeated dosing. Mode of action studies showed that afoxolaner blocked native and expressed insect GABA-gated chloride channels with nanomolar potency. Afoxolaner has comparable potency between wild type channels and channels possessing the A302S (resistance-to-dieldrin) mutation. Lack of cyclodiene cross-resistance for afoxolaner was confirmed in comparative Drosophila toxicity studies, and it is concluded that afoxolaner blocked GABA-gated chloride channels via a site distinct from the cyclodienes. Copyright © 2014 The Authors. Published by Elsevier B.V. All rights reserved.
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            Current trends in the treatment of Sarcoptes, Cheyletiella and Otodectes mite infestations in dogs and cats.

            For a number of reasons, several of the more 'traditional' ectoparasiticides in the small animal veterinarian's armoury have been withdrawn over the past few years. New, safer products which are long-acting and easier to apply than the conventional dips, rinses and aerosol sprays of the past have replaced them. However, relatively few such novel acaricidal preparations have become commercially available. Consequently, practitioners and researchers frequently experiment with the drugs they have at their disposal to assess their efficacy against a variety of target acarids when used at different dosages and/or via different routes of administration, compared with those recommended by the manufacturer. This paper reviews the anecdotal and peer-reviewed reports describing the use of modern acaricides in dogs and cats that have recently appeared in the veterinary literature. It should be stressed, however, that no medicine should be prescribed for extra-label use without the informed consent of the owner.
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              Efficacy of oral afoxolaner for the treatment of canine generalised demodicosis

              The efficacy of oral treatment with a chewable tablet containing afoxolaner 2.27% w/w (NexGard®, Merial) administered orally was assessed in eight dogs diagnosed with generalised demodicosis and compared with efficacy in eight dogs under treatment with a topical combination of imidacloprid/moxidectin (Advocate®, Bayer). Afoxolaner was administered at the recommended dose (at least 2.5 mg/kg) on Days 0, 14, 28 and 56. The topical combination of imidacloprid/moxidectin was given at the same intervals at the recommended concentration. Clinical examinations and deep skin scrapings were performed every month in order to evaluate the effect on mite numbers and the resolution of clinical signs. The percentage reductions of mite counts were 99.2%, 99.9% and 100% on Days 28, 56 and 84, respectively, in the afoxolaner-treated group, compared to 89.8%, 85.2% and 86.6% on Days 28, 56 and 84 in the imidacloprid/moxidectin-treated group. Skin condition of the dogs also improved significantly from Day 28 to Day 84 in the afoxolaner-treated group. Mite reductions were significantly higher on Days 28, 56 and 84 in the afoxolaner-treated group compared to the imidacloprid/moxidectin-treated group. The results of this study demonstrated that afoxolaner, given orally, was effective in treating dogs with generalised demodicosis within a two-month period.
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                Author and article information

                Contributors
                doug.carithers@Merial.com
                jordan.crawford@merial.com
                Christa.deVos@clinvet.com
                alta.lotriet@clinvet.com
                Josephus.Fourie@clinvet.com
                Journal
                Parasit Vectors
                Parasit Vectors
                Parasites & Vectors
                BioMed Central (London )
                1756-3305
                9 December 2016
                9 December 2016
                2016
                : 9
                : 635
                Affiliations
                [1 ]Merial, Inc, 3239 Satellite Blvd, Duluth, 30096 GA USA
                [2 ]Clinvet International (Pty) Ltd, PO Box 111869321, Universitas, South Africa
                Article
                1924
                10.1186/s13071-016-1924-4
                5148825
                27938395
                34bb9720-797e-4311-90ac-bbb869686af8
                © The Author(s). 2016

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 3 October 2016
                : 1 December 2016
                Funding
                Funded by: Merial, Inc.
                Categories
                Research
                Custom metadata
                © The Author(s) 2016

                Parasitology
                otodectes cynotis,dog,afoxolaner,nexgard
                Parasitology
                otodectes cynotis, dog, afoxolaner, nexgard

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