Preclinical Study of Single-Dose Moxidectin, a New Oral Treatment for Scabies: Efficacy, Safety, and Pharmacokinetics Compared to Two-Dose Ivermectin in a Porcine Model.

Scabies is one of the commonest dermatological conditions globally; however it is a largely underexplored and truly neglected infectious disease. Foremost, improvement in the management of this public health burden is imperative. Current treatments with topical agents and/or oral ivermectin (IVM) ar...

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Main Authors: Charlotte Bernigaud, Fang Fang, Katja Fischer, Anne Lespine, Ludwig Serge Aho, Dominique Dreau, Andrew Kelly, Jean-François Sutra, Francis Moreau, Thomas Lilin, Françoise Botterel, Jacques Guillot, Olivier Chosidow
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2016-10-01
Series:PLoS Neglected Tropical Diseases
Online Access:http://europepmc.org/articles/PMC5061321?pdf=render
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spelling doaj-547e2ac3c77c49dfb14aeb33856e81502020-11-25T02:04:19ZengPublic Library of Science (PLoS)PLoS Neglected Tropical Diseases1935-27271935-27352016-10-011010e000503010.1371/journal.pntd.0005030Preclinical Study of Single-Dose Moxidectin, a New Oral Treatment for Scabies: Efficacy, Safety, and Pharmacokinetics Compared to Two-Dose Ivermectin in a Porcine Model.Charlotte BernigaudFang FangKatja FischerAnne LespineLudwig Serge AhoDominique DreauAndrew KellyJean-François SutraFrancis MoreauThomas LilinFrançoise BotterelJacques GuillotOlivier ChosidowScabies is one of the commonest dermatological conditions globally; however it is a largely underexplored and truly neglected infectious disease. Foremost, improvement in the management of this public health burden is imperative. Current treatments with topical agents and/or oral ivermectin (IVM) are insufficient and drug resistance is emerging. Moxidectin (MOX), with more advantageous pharmacological profiles may be a promising alternative.Using a porcine scabies model, 12 pigs were randomly assigned to receive orally either MOX (0.3 mg/kg once), IVM (0.2 mg/kg twice) or no treatment. We evaluated treatment efficacies by assessing mite count, clinical lesions, pruritus and ELISA-determined anti-S. scabiei IgG antibodies reductions. Plasma and skin pharmacokinetic profiles were determined. At day 14 post-treatment, all four MOX-treated but only two IVM-treated pigs were mite-free. MOX efficacy was 100% and remained unchanged until study-end (D47), compared to 62% (range 26-100%) for IVM, with one IVM-treated pig remaining infected until D47. Clinical scabies lesions, pruritus and anti-S. scabiei IgG antibodies had completely disappeared in all MOX-treated but only 75% of IVM-treated pigs. MOX persisted ~9 times longer than IVM in plasma and skin, thereby covering the mite's entire life cycle and enabling long-lasting efficacy.Our data demonstrate that oral single-dose MOX was more effective than two consecutive IVM-doses, supporting MOX as potential therapeutic approach for scabies.http://europepmc.org/articles/PMC5061321?pdf=render
collection DOAJ
language English
format Article
sources DOAJ
author Charlotte Bernigaud
Fang Fang
Katja Fischer
Anne Lespine
Ludwig Serge Aho
Dominique Dreau
Andrew Kelly
Jean-François Sutra
Francis Moreau
Thomas Lilin
Françoise Botterel
Jacques Guillot
Olivier Chosidow
spellingShingle Charlotte Bernigaud
Fang Fang
Katja Fischer
Anne Lespine
Ludwig Serge Aho
Dominique Dreau
Andrew Kelly
Jean-François Sutra
Francis Moreau
Thomas Lilin
Françoise Botterel
Jacques Guillot
Olivier Chosidow
Preclinical Study of Single-Dose Moxidectin, a New Oral Treatment for Scabies: Efficacy, Safety, and Pharmacokinetics Compared to Two-Dose Ivermectin in a Porcine Model.
PLoS Neglected Tropical Diseases
author_facet Charlotte Bernigaud
Fang Fang
Katja Fischer
Anne Lespine
Ludwig Serge Aho
Dominique Dreau
Andrew Kelly
Jean-François Sutra
Francis Moreau
Thomas Lilin
Françoise Botterel
Jacques Guillot
Olivier Chosidow
author_sort Charlotte Bernigaud
title Preclinical Study of Single-Dose Moxidectin, a New Oral Treatment for Scabies: Efficacy, Safety, and Pharmacokinetics Compared to Two-Dose Ivermectin in a Porcine Model.
title_short Preclinical Study of Single-Dose Moxidectin, a New Oral Treatment for Scabies: Efficacy, Safety, and Pharmacokinetics Compared to Two-Dose Ivermectin in a Porcine Model.
title_full Preclinical Study of Single-Dose Moxidectin, a New Oral Treatment for Scabies: Efficacy, Safety, and Pharmacokinetics Compared to Two-Dose Ivermectin in a Porcine Model.
title_fullStr Preclinical Study of Single-Dose Moxidectin, a New Oral Treatment for Scabies: Efficacy, Safety, and Pharmacokinetics Compared to Two-Dose Ivermectin in a Porcine Model.
title_full_unstemmed Preclinical Study of Single-Dose Moxidectin, a New Oral Treatment for Scabies: Efficacy, Safety, and Pharmacokinetics Compared to Two-Dose Ivermectin in a Porcine Model.
title_sort preclinical study of single-dose moxidectin, a new oral treatment for scabies: efficacy, safety, and pharmacokinetics compared to two-dose ivermectin in a porcine model.
publisher Public Library of Science (PLoS)
series PLoS Neglected Tropical Diseases
issn 1935-2727
1935-2735
publishDate 2016-10-01
description Scabies is one of the commonest dermatological conditions globally; however it is a largely underexplored and truly neglected infectious disease. Foremost, improvement in the management of this public health burden is imperative. Current treatments with topical agents and/or oral ivermectin (IVM) are insufficient and drug resistance is emerging. Moxidectin (MOX), with more advantageous pharmacological profiles may be a promising alternative.Using a porcine scabies model, 12 pigs were randomly assigned to receive orally either MOX (0.3 mg/kg once), IVM (0.2 mg/kg twice) or no treatment. We evaluated treatment efficacies by assessing mite count, clinical lesions, pruritus and ELISA-determined anti-S. scabiei IgG antibodies reductions. Plasma and skin pharmacokinetic profiles were determined. At day 14 post-treatment, all four MOX-treated but only two IVM-treated pigs were mite-free. MOX efficacy was 100% and remained unchanged until study-end (D47), compared to 62% (range 26-100%) for IVM, with one IVM-treated pig remaining infected until D47. Clinical scabies lesions, pruritus and anti-S. scabiei IgG antibodies had completely disappeared in all MOX-treated but only 75% of IVM-treated pigs. MOX persisted ~9 times longer than IVM in plasma and skin, thereby covering the mite's entire life cycle and enabling long-lasting efficacy.Our data demonstrate that oral single-dose MOX was more effective than two consecutive IVM-doses, supporting MOX as potential therapeutic approach for scabies.
url http://europepmc.org/articles/PMC5061321?pdf=render
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