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...
Main Authors: | , , , , , , , , , , , , |
---|---|
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 |
id |
doaj-547e2ac3c77c49dfb14aeb33856e8150 |
---|---|
record_format |
Article |
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 |
work_keys_str_mv |
AT charlottebernigaud preclinicalstudyofsingledosemoxidectinaneworaltreatmentforscabiesefficacysafetyandpharmacokineticscomparedtotwodoseivermectininaporcinemodel AT fangfang preclinicalstudyofsingledosemoxidectinaneworaltreatmentforscabiesefficacysafetyandpharmacokineticscomparedtotwodoseivermectininaporcinemodel AT katjafischer preclinicalstudyofsingledosemoxidectinaneworaltreatmentforscabiesefficacysafetyandpharmacokineticscomparedtotwodoseivermectininaporcinemodel AT annelespine preclinicalstudyofsingledosemoxidectinaneworaltreatmentforscabiesefficacysafetyandpharmacokineticscomparedtotwodoseivermectininaporcinemodel AT ludwigsergeaho preclinicalstudyofsingledosemoxidectinaneworaltreatmentforscabiesefficacysafetyandpharmacokineticscomparedtotwodoseivermectininaporcinemodel AT dominiquedreau preclinicalstudyofsingledosemoxidectinaneworaltreatmentforscabiesefficacysafetyandpharmacokineticscomparedtotwodoseivermectininaporcinemodel AT andrewkelly preclinicalstudyofsingledosemoxidectinaneworaltreatmentforscabiesefficacysafetyandpharmacokineticscomparedtotwodoseivermectininaporcinemodel AT jeanfrancoissutra preclinicalstudyofsingledosemoxidectinaneworaltreatmentforscabiesefficacysafetyandpharmacokineticscomparedtotwodoseivermectininaporcinemodel AT francismoreau preclinicalstudyofsingledosemoxidectinaneworaltreatmentforscabiesefficacysafetyandpharmacokineticscomparedtotwodoseivermectininaporcinemodel AT thomaslilin preclinicalstudyofsingledosemoxidectinaneworaltreatmentforscabiesefficacysafetyandpharmacokineticscomparedtotwodoseivermectininaporcinemodel AT francoisebotterel preclinicalstudyofsingledosemoxidectinaneworaltreatmentforscabiesefficacysafetyandpharmacokineticscomparedtotwodoseivermectininaporcinemodel AT jacquesguillot preclinicalstudyofsingledosemoxidectinaneworaltreatmentforscabiesefficacysafetyandpharmacokineticscomparedtotwodoseivermectininaporcinemodel AT olivierchosidow preclinicalstudyofsingledosemoxidectinaneworaltreatmentforscabiesefficacysafetyandpharmacokineticscomparedtotwodoseivermectininaporcinemodel |
_version_ |
1724943062427238400 |