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

• Published in: PLoS neglected tropical diseases 2016-10, Vol.10 (10), p.e0005030-e0005030
• Main Authors: Bernigaud, Charlotte, Fang, Fang, Fischer, Katja, Lespine, Anne, Aho, Ludwig Serge, Dreau, Dominique, Kelly, Andrew, Sutra, Jean-François, Moreau, Francis, Lilin, Thomas, Botterel, Françoise, Guillot, Jacques, Chosidow, Olivier
• Format: Article
• Language: English
• Subjects: Acaricides - administration & dosage; Acaricides - adverse effects; Acaricides - pharmacokinetics; Administration, Oral; Animal sciences; Animals; Biology and Life Sciences; Compliance; Complications and side effects; Dermatology; Disease; Dosage and administration; Drug dosages; Drug Evaluation, Preclinical; Drug resistance; Drug therapy; Feasibility studies; Female; Funding; Hogs; Humans; Infections; Infectious diseases; Ivermectin; Ivermectin - administration & dosage; Ivermectin - adverse effects; Ivermectin - pharmacokinetics; Lesions; Macrolides - administration & dosage; Macrolides - adverse effects; Macrolides - pharmacokinetics; Medicine and Health Sciences; Mites; Models, Animal; Parasitology; Patient outcomes; Pharmacokinetics; Pruritus; Public health; Research and Analysis Methods; Sabatier, Paul (1854-1941); Sarcoptes scabiei - drug effects; Scabies; Scabies - drug therapy; Social Sciences; Swine; Tropical diseases; Zoology
• ISSN: 1935-2735; 1935-2727; 1935-2735
• DOI: 10.1371/journal.pntd.0005030

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.