Research Group Dynamyc, EA7380, Université Paris-Est Créteil, Créteil, France
Department of Dermatology, AP-HP, Hôpital Henri Mondor, Université Paris-Est, Créteil, France.
Antimicrob Agents Chemother. 2018 Aug 27;62(9). doi: 10.1128/AAC.02334-17. Print 2018 Sep.
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 either treated with 2.5 mg/kg single dose oral AFX ( = 4) or 0.2 mg/kg, two doses 8 days apart, oral ivermectin ([IVM] = 4) or not treated for scabies ( = 4). The response to treatment was assessed by the reduction of mite counts in skin scrapings as well as clinical and pruritus scores over time. Plasma and skin pharmacokinetics profiles for both AFX and IVM were evaluated. AFX efficacy was 100% at days 8 and 14 posttreatment 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 the 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 remarkably long MRTs in plasma and, notably, in the skin.
疥疮是一个全球性的重大且潜在的公共卫生问题，需要一种具有更高疗效和改善药理学特性的杀螨剂来满足其治疗需求。本研究的目的是评估一种新型杀螨剂阿福拉纳（AFX）在相关实验性猪模型中的疗效，并描述其药代动力学特征。12 头猪进行了实验性感染，然后给予 2.5mg/kg 单剂量口服 AFX（n=4）、0.2mg/kg，2 剂，间隔 8 天，口服伊维菌素（n=4）或不治疗疥疮（n=4）。通过皮肤刮片减少螨虫计数以及随时间变化的临床和瘙痒评分来评估治疗反应。评估了 AFX 和伊维菌素的血浆和皮肤药代动力学特征。AFX 在治疗后第 8 天和第 14 天的疗效为 100%，直到研究结束（第 45 天）未发生变化。伊维菌素在第 8 天和第 14 天的疗效分别为 86%和 97%，在研究结束时仍有少量螨虫存活。两组治疗组的临床和瘙痒评分均降低，对照组保持不变。AFX 和伊维菌素的血浆平均驻留时间（MRT）分别为 7.1±2.4 天和 1.1±0.2 天。AFX 和伊维菌素的皮肤 MRT 值分别为 16.2±16.9 天和 2.7±0.5 天。总的来说，单次口服 AFX 对实验性感染猪的疥疮治疗有效，且在血浆中以及显著在皮肤中表现出显著的长 MRT。
