Efficacy and pharmacokinetics evaluation of a single oral dose of afoxolaner against Sarcoptes scabiei in the porcine Scabies model for human infestation

Charlotte Bernigaud (1, 2, 3) , Fang Fang (1, 2, 4) , Katja Fischer (5) , Anne Lespine (6) , Ludwig S. Aho (7) , Amanda J. Mullins (8) , Berhane Tecle (9) , Andrew Kelly (10) , Jean-Francois Sutra (11) , Francis Moreau (12) , Thomas Lilin (12) , Frédéric Beugnet (13) , Françoise Botterel (1, 2, 3) , Olivier Chosidow (3, 14) , Jacques Guillot (1, 2)

1 ENVA - École nationale vétérinaire d'Alfort
2 Université Paris Est Créteil
3 Groupe Hospitalier des Hôpitaux Universitaires de l’Est Parisien
4 Department of Parasitology, College of Animal Science and Technology
5 QIMR Berghofer Medical Research Institute
6 InTheRes - Innovations Thérapeutiques et Résistances
7 Epidemiology and Infection Control Unit
8 Merial Inc.
9 Boehringer Ingelheim Animal Health
10 UQ [All campuses : Brisbane, Dutton Park Gatton, Herston, St Lucia and other locations] - The University of Queensland
11 ToxAlim - ToxAlim
12 CRBM - Centre de recherche biomédicale
13 Merial France
14 INSERM - Institut National de la Santé et de la Recherche Médicale

Scabies is a major and potentially growing public health problem worldwide with an unmet need for acaricidal agents with greater efficacy and improved pharmacological properties for its treatment. The objective of the present study was to assess the efficacy and describe the pharmacokinetics profile of a novel acaricide, afoxolaner (AFX), in a relevant experimental porcine model. Twelve pigs were experimentally infested and treated either with 2.5 mg/kg single dose oral AFX (n = 4), 0.2 mg/kg two-doses 8 days apart oral ivermectin (IVM, n = 4), or no treatment against scabies (n = 4). Response to treatment was assessed by reduction of mite counts in skin scrapings as well as clinical and pruritus scores over time. Plasma and skin pharmacokinetic profiles for both AFX and IVM were evaluated. AFX efficacy was 100% at days 8 and 14 post-treatment and remained unchanged until the study-end (day 45). IVM efficacy was 86% and 97% on days 8 and 14, respectively, with a few mites recovered at study-end. Clinical and pruritus scores decreased in both treated groups and remained constant in the control group. Plasma mean residence times (MRT) were 7.1±2.4 and 1.1±0.2 days for AFX and IVM, respectively. Skin MRT values were 16.2±16.9 and 2.7±0.5 days for AFX and IVM, respectively. Overall, a single oral dose of AFX was efficacious for the treatment of scabies in experimentally infested pigs and showed a remarkably long MRT in plasma and notably in the skin.

Mots clés: isoxazoline; ivermectin

Mots clés: scabies; afoxolaner; acaricide agent; porcine model

Domaines: Sciences du Vivant [q-bio]

Charlotte Bernigaud, Fang Fang, Katja Fischer, Anne Lespine, Ludwig S. Aho, et al.. Efficacy and pharmacokinetics evaluation of a single oral dose of afoxolaner against Sarcoptes scabiei in the porcine Scabies model for human infestation. Antimicrobial Agents and Chemotherapy, 2018, 62 (9), ⟨10.1128/AAC.02334-17⟩. ⟨hal-02627327⟩