Département de pathologie et microbiologie, Faculté de médecine vétérinaire, Université de Montréal, Saint-Hyacinthe, Québec, Canada.
Groupe de recherche en épidémiologie des zoonoses et santé publique, Faculté de médecine vétérinaire, Université de Montréal, Saint-Hyacinthe, Québec, Canada.
Sci Rep. 2024 Jun 12;14(1):13537. doi: 10.1038/s41598-024-63799-x.
The development of interventions targeting reservoirs of Borrelia burgdorferi sensu stricto with acaricide to reduce the density of infected ticks faces numerous challenges imposed by ecological and operational limits. In this study, the pharmacokinetics, efficacy and toxicology of fluralaner were investigated in Mus musculus and Peromyscus leucopus mice, the main reservoir of B. burgdorferi in North America. Fluralaner showed rapid distribution and elimination, leading to fast plasma concentration (C) depletion in the first hours after administration followed by a slow elimination rate for several weeks, resulting in a long terminal half-life. Efficacy fell below 100% while C (± standard deviation) decreased from 196 ± 54 to 119 ± 62 ng/mL. These experimental results were then used in simulations of fluralaner treatment for a duration equivalent to the active period of Ixodes scapularis larvae and nymphs. Simulations showed that doses as low as 10 mg/kg have the potential to protect P. leucopus against infestation for a full I. scapularis active season if administered at least once every 7 days. This study shows that investigating the pharmacology of candidate acaricides in combination with pharmacokinetic simulations can provide important information to support the development of effective interventions targeting ecological reservoirs of Lyme disease. It therefore represents a critical step that may help surpass limits inherent to the development of these interventions.
针对伯氏疏螺旋体严格意义上的储层（以蜱为媒介），使用杀螨剂来降低感染蜱的密度，以减少莱姆病的生态储层，这种干预措施的发展面临着生态和操作限制带来的诸多挑战。在这项研究中，我们研究了氟雷拉纳在 Mus musculus 和 Peromyscus leucopus 小鼠中的药代动力学、疗效和毒理学，这两种啮齿动物是北美的主要伯氏疏螺旋体储层。氟雷拉纳表现出快速的分布和消除，导致在给药后的最初几个小时内血浆浓度（C）迅速耗尽，随后几周内消除速度缓慢，导致半衰期延长。当 C（±标准偏差）从 196±54 降至 119±62ng/mL 时，疗效下降至 100%以下。这些实验结果随后用于模拟氟雷拉纳治疗，持续时间相当于伊氏扇头蜱幼虫和若虫的活动期。模拟结果表明，如果每 7 天至少给药一次，低至 10mg/kg 的剂量就有可能保护白足鼠免受伊氏扇头蜱的侵害，从而度过整个伊氏扇头蜱的活跃季节。本研究表明，结合药代动力学模拟研究候选杀螨剂的药理学可以提供重要信息，支持针对莱姆病生态储层的有效干预措施的开发。因此，这代表了一个关键步骤，可能有助于克服这些干预措施发展所固有的限制。
