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 Negl Trop Dis. 2016 Oct 12;10(10):e0005030. doi: 10.1371/journal.pntd.0005030. eCollection 2016 Oct.

Abstract

Background: 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.

Methodology/principal findings: 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.

Conclusions/significance: Our data demonstrate that oral single-dose MOX was more effective than two consecutive IVM-doses, supporting MOX as potential therapeutic approach for scabies.

Publication types

  • Comparative Study

MeSH terms

  • 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

Substances

  • Acaricides
  • Macrolides
  • Ivermectin
  • moxidectin

Grants and funding

This work was supported by a research grant from the Société Française de Dermatologie. CB was able to learn the Australian model with a short-term travel grant from the Fondation René Touraine. FF is supported by the Fund of the China Scholarship Council. We are grateful to the philanthropic crowdfunding from kisskissbankers (https://www.kisskissbankbank.com/soutenez-ma-these-de-recherche-sur-la-gale) for their help in the feasibility study. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.