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
Identifieur interne : 001923 ( Main/Exploration ); précédent : 001922; suivant : 001924Preclinical Study of Single-Dose Moxidectin, a New Oral Treatment for Scabies: Efficacy, Safety, and Pharmacokinetics Compared to Two-Dose Ivermectin in a Porcine Model
Auteurs : Charlotte Bernigaud [France] ; Fang Fang [France, République populaire de Chine] ; Katja Fischer [Australie] ; Anne Lespine [France] ; Ludwig Serge Aho [France] ; Dominique Dreau [France] ; Andrew Kelly [Australie] ; Jean-François Sutra [France] ; Francis Moreau [France] ; Thomas Lilin [France] ; Françoise Botterel [France] ; Jacques Guillot [France] ; Olivier Chosidow [France]Source :
- PLoS Neglected Tropical Diseases [ 1935-2727 ] ; 2016.
Descripteurs français
- KwdFr :
- Acaricides (administration et posologie), Acaricides (effets indésirables), Acaricides (pharmacocinétique), Administration par voie orale, Animaux, Femelle, Gale (traitement médicamenteux), Humains, Ivermectine (administration et posologie), Ivermectine (effets indésirables), Ivermectine (pharmacocinétique), Macrolides (administration et posologie), Macrolides (effets indésirables), Macrolides (pharmacocinétique), Modèles animaux, Sarcopte scabiei (), Suidae, Évaluation préclinique de médicament.
- MESH :
- administration et posologie : Acaricides, Ivermectine, Macrolides.
- effets indésirables : Acaricides, Ivermectine, Macrolides.
- pharmacocinétique : Acaricides, Ivermectine, Macrolides.
- traitement médicamenteux : Gale.
- Administration par voie orale, Animaux, Femelle, Humains, Modèles animaux, Sarcopte scabiei, Suidae, Évaluation préclinique de médicament.
English descriptors
- KwdEn :
- Acaricides (administration & dosage), Acaricides (adverse effects), Acaricides (pharmacokinetics), Administration, Oral, Animals, Drug Evaluation, Preclinical, Female, Humans, Ivermectin (administration & dosage), Ivermectin (adverse effects), Ivermectin (pharmacokinetics), Macrolides (administration & dosage), Macrolides (adverse effects), Macrolides (pharmacokinetics), Models, Animal, Sarcoptes scabiei (drug effects), Scabies (drug therapy), Swine.
- MESH :
- chemical , administration & dosage : Acaricides, Ivermectin, Macrolides.
- chemical , adverse effects : Acaricides, Ivermectin, Macrolides.
- chemical , pharmacokinetics : Acaricides, Ivermectin, Macrolides.
- drug effects : Sarcoptes scabiei.
- drug therapy : Scabies.
- Administration, Oral, Animals, Drug Evaluation, Preclinical, Female, Humans, Models, Animal, Swine.
Abstract
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-
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:
DOI: 10.1371/journal.pntd.0005030
PubMed: 27732588
PubMed Central: 5061321
Affiliations:
- Australie, France, République populaire de Chine
- Bourgogne, Bourgogne-Franche-Comté, Midi-Pyrénées, Occitanie (région administrative), Île-de-France
- Créteil, Dijon, Toulouse
Links toward previous steps (curation, corpus...)
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- to stream PubMed, to step Corpus: 001799
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- to stream Ncbi, to step Merge: 003C98
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Le document en format XML
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<author><name sortKey="Sutra, Jean Francois" sort="Sutra, Jean Francois" uniqKey="Sutra J" first="Jean-François" last="Sutra">Jean-François Sutra</name>
<affiliation wicri:level="3"><nlm:aff id="aff005"><addr-line>Toxalim, INRA, INP-ENVT, INP-EI-Purpan, Université de Toulouse III Paul Sabatier, Toulouse, France</addr-line>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>Toxalim, INRA, INP-ENVT, INP-EI-Purpan, Université de Toulouse III Paul Sabatier, Toulouse</wicri:regionArea>
<placeName><region type="region">Occitanie (région administrative)</region>
<region type="old region">Midi-Pyrénées</region>
<settlement type="city">Toulouse</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Moreau, Francis" sort="Moreau, Francis" uniqKey="Moreau F" first="Francis" last="Moreau">Francis Moreau</name>
<affiliation wicri:level="1"><nlm:aff id="aff009"><addr-line>Centre de Recherche BioMédicale (CRBM), EnvA, UPE, Maisons-Alfort, France</addr-line>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>Centre de Recherche BioMédicale (CRBM), EnvA, UPE, Maisons-Alfort</wicri:regionArea>
<wicri:noRegion>Maisons-Alfort</wicri:noRegion>
<wicri:noRegion>Maisons-Alfort</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Lilin, Thomas" sort="Lilin, Thomas" uniqKey="Lilin T" first="Thomas" last="Lilin">Thomas Lilin</name>
<affiliation wicri:level="1"><nlm:aff id="aff009"><addr-line>Centre de Recherche BioMédicale (CRBM), EnvA, UPE, Maisons-Alfort, France</addr-line>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>Centre de Recherche BioMédicale (CRBM), EnvA, UPE, Maisons-Alfort</wicri:regionArea>
<wicri:noRegion>Maisons-Alfort</wicri:noRegion>
<wicri:noRegion>Maisons-Alfort</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Botterel, Francoise" sort="Botterel, Francoise" uniqKey="Botterel F" first="Françoise" last="Botterel">Françoise Botterel</name>
<affiliation wicri:level="1"><nlm:aff id="aff001"><addr-line>Research Group Dynamyc, EA 7380, EnvA, Université Paris-Est (UPE), Maisons-Alfort & Créteil, France</addr-line>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>Research Group Dynamyc, EA 7380, EnvA, Université Paris-Est (UPE), Maisons-Alfort & Créteil</wicri:regionArea>
<wicri:noRegion>Maisons-Alfort & Créteil</wicri:noRegion>
<wicri:noRegion>Maisons-Alfort & Créteil</wicri:noRegion>
</affiliation>
<affiliation wicri:level="3"><nlm:aff id="aff010"><addr-line>APHP, Hôpital Henri-Mondor, Parasitology and Mycology, Department of Microbiology, DHU VIC, UPEC, Créteil, France</addr-line>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>APHP, Hôpital Henri-Mondor, Parasitology and Mycology, Department of Microbiology, DHU VIC, UPEC, Créteil</wicri:regionArea>
<placeName><region type="region">Île-de-France</region>
<region type="old region">Île-de-France</region>
<settlement type="city">Créteil</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Guillot, Jacques" sort="Guillot, Jacques" uniqKey="Guillot J" first="Jacques" last="Guillot">Jacques Guillot</name>
<affiliation wicri:level="1"><nlm:aff id="aff001"><addr-line>Research Group Dynamyc, EA 7380, EnvA, Université Paris-Est (UPE), Maisons-Alfort & Créteil, France</addr-line>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>Research Group Dynamyc, EA 7380, EnvA, Université Paris-Est (UPE), Maisons-Alfort & Créteil</wicri:regionArea>
<wicri:noRegion>Maisons-Alfort & Créteil</wicri:noRegion>
<wicri:noRegion>Maisons-Alfort & Créteil</wicri:noRegion>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="aff011"><addr-line>Department of Parasitology and Mycology, Biopôle d'Alfort, Ecole nationale vétérinaire d'Alfort, UPE, Maisons-Alfort, France</addr-line>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>Department of Parasitology and Mycology, Biopôle d'Alfort, Ecole nationale vétérinaire d'Alfort, UPE, Maisons-Alfort</wicri:regionArea>
<wicri:noRegion>Maisons-Alfort</wicri:noRegion>
<wicri:noRegion>Maisons-Alfort</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Chosidow, Olivier" sort="Chosidow, Olivier" uniqKey="Chosidow O" first="Olivier" last="Chosidow">Olivier Chosidow</name>
<affiliation wicri:level="3"><nlm:aff id="aff002"><addr-line>APHP, Hôpital Henri-Mondor, Department of Dermatology, UPEC, Créteil, France</addr-line>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>APHP, Hôpital Henri-Mondor, Department of Dermatology, UPEC, Créteil</wicri:regionArea>
<placeName><region type="region">Île-de-France</region>
<region type="old region">Île-de-France</region>
<settlement type="city">Créteil</settlement>
</placeName>
</affiliation>
<affiliation wicri:level="3"><nlm:aff id="aff012"><addr-line>EA EpiDermE (Epidémiologie en Dermatologie et Evaluation des Thérapeutiques) and INSERM, CIC 1430, UPE, Créteil, France</addr-line>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>EA EpiDermE (Epidémiologie en Dermatologie et Evaluation des Thérapeutiques) and INSERM, CIC 1430, UPE, Créteil</wicri:regionArea>
<placeName><region type="region">Île-de-France</region>
<region type="old region">Île-de-France</region>
<settlement type="city">Créteil</settlement>
</placeName>
</affiliation>
</author>
</analytic>
<series><title level="j">PLoS Neglected Tropical Diseases</title>
<idno type="ISSN">1935-2727</idno>
<idno type="eISSN">1935-2735</idno>
<imprint><date when="2016">2016</date>
</imprint>
</series>
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<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Acaricides (administration & dosage)</term>
<term>Acaricides (adverse effects)</term>
<term>Acaricides (pharmacokinetics)</term>
<term>Administration, Oral</term>
<term>Animals</term>
<term>Drug Evaluation, Preclinical</term>
<term>Female</term>
<term>Humans</term>
<term>Ivermectin (administration & dosage)</term>
<term>Ivermectin (adverse effects)</term>
<term>Ivermectin (pharmacokinetics)</term>
<term>Macrolides (administration & dosage)</term>
<term>Macrolides (adverse effects)</term>
<term>Macrolides (pharmacokinetics)</term>
<term>Models, Animal</term>
<term>Sarcoptes scabiei (drug effects)</term>
<term>Scabies (drug therapy)</term>
<term>Swine</term>
</keywords>
<keywords scheme="KwdFr" xml:lang="fr"><term>Acaricides (administration et posologie)</term>
<term>Acaricides (effets indésirables)</term>
<term>Acaricides (pharmacocinétique)</term>
<term>Administration par voie orale</term>
<term>Animaux</term>
<term>Femelle</term>
<term>Gale (traitement médicamenteux)</term>
<term>Humains</term>
<term>Ivermectine (administration et posologie)</term>
<term>Ivermectine (effets indésirables)</term>
<term>Ivermectine (pharmacocinétique)</term>
<term>Macrolides (administration et posologie)</term>
<term>Macrolides (effets indésirables)</term>
<term>Macrolides (pharmacocinétique)</term>
<term>Modèles animaux</term>
<term>Sarcopte scabiei ()</term>
<term>Suidae</term>
<term>Évaluation préclinique de médicament</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="administration & dosage" xml:lang="en"><term>Acaricides</term>
<term>Ivermectin</term>
<term>Macrolides</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="adverse effects" xml:lang="en"><term>Acaricides</term>
<term>Ivermectin</term>
<term>Macrolides</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="pharmacokinetics" xml:lang="en"><term>Acaricides</term>
<term>Ivermectin</term>
<term>Macrolides</term>
</keywords>
<keywords scheme="MESH" qualifier="administration et posologie" xml:lang="fr"><term>Acaricides</term>
<term>Ivermectine</term>
<term>Macrolides</term>
</keywords>
<keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Sarcoptes scabiei</term>
</keywords>
<keywords scheme="MESH" qualifier="drug therapy" xml:lang="en"><term>Scabies</term>
</keywords>
<keywords scheme="MESH" qualifier="effets indésirables" xml:lang="fr"><term>Acaricides</term>
<term>Ivermectine</term>
<term>Macrolides</term>
</keywords>
<keywords scheme="MESH" qualifier="pharmacocinétique" xml:lang="fr"><term>Acaricides</term>
<term>Ivermectine</term>
<term>Macrolides</term>
</keywords>
<keywords scheme="MESH" qualifier="traitement médicamenteux" xml:lang="fr"><term>Gale</term>
</keywords>
<keywords scheme="MESH" xml:lang="en"><term>Administration, Oral</term>
<term>Animals</term>
<term>Drug Evaluation, Preclinical</term>
<term>Female</term>
<term>Humans</term>
<term>Models, Animal</term>
<term>Swine</term>
</keywords>
<keywords scheme="MESH" xml:lang="fr"><term>Administration par voie orale</term>
<term>Animaux</term>
<term>Femelle</term>
<term>Humains</term>
<term>Modèles animaux</term>
<term>Sarcopte scabiei</term>
<term>Suidae</term>
<term>Évaluation préclinique de médicament</term>
</keywords>
</textClass>
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<front><div type="abstract" xml:lang="en"><sec id="sec001"><title>Background</title>
<p>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.</p>
</sec>
<sec id="sec002"><title>Methodology/Principal Findings</title>
<p>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-<italic>S</italic>
. <italic>scabiei</italic>
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-<italic>S</italic>
. <italic>scabiei</italic>
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.</p>
</sec>
<sec id="sec003"><title>Conclusions/Significance</title>
<p>Our data demonstrate that oral single-dose MOX was more effective than two consecutive IVM-doses, supporting MOX as potential therapeutic approach for scabies.</p>
</sec>
</div>
</front>
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