Elanco Animal Health, Mattenstrasse 24a, CH-4058, Basel, Switzerland.
Elanco Animal Health, 2500 Innovation Way, Greenfield, IN, 46140, USA.
Parasit Vectors. 2018 Jul 13;11(1):409. doi: 10.1186/s13071-018-2969-3.
Lotilaner is a new member of the isoxazoline class for treatment of flea and tick infestations in cats. This laboratory study with lotilaner vanilla-yeast flavoured chewable tablets (Credelio, Elanco) investigated the safety in healthy kittens starting at 8 weeks of age in a randomized, blinded, parallel-group design. Lotilaner tablets were given orally once a month over eight months at one, three and five times the upper level of the maximum recommended dose range (26 mg/kg).
The safety of lotilaner flavoured chewable tablets was assessed in healthy kittens when administered orally every 4 weeks for 8 months at the highest recommended dose rates, i.e. 1× (26 mg/kg) and at elevated dose rates, i.e. 3× (78 mg/kg) and 5× (130 mg/kg). Sixteen male and 16 female healthy 8-week-old kittens, with a mean body weight of 0.79 kg and 0.75 kg, respectively, were randomized to an untreated control group or lotilaner groups at dose rates of 26 mg/kg (1×), 78 mg/kg (3×), or 130 mg/kg (5×) every four weeks over eight months. The control group was sham-dosed. All animals were fed within 30 minutes prior to treatment. Safety assessment included general health observations, detailed clinical observations, complete physical/neurological examinations, including ophthalmological examinations, electrocardiographic (ECG) and clinical pathology evaluations (haematology, clinical chemistry and urinalysis), food and water consumption, body weight, pharmacokinetic blood collections, organ macroscopic and microscopic examinations.
Systemic exposure to lotilaner was confirmed during the course of the study in all treated animals with the exception of the control group. No treatment-related effects were seen on daily clinical observations, food consumption (wet), ophthalmoscopic, physical/neurological and microscopic examinations. Statistically significant differences were recorded in some of the clinical pathology parameters, body weights, food consumption (dry), electrocardiograms, and organ weights, but none of the recorded observations was considered to be of clinical relevance.
Lotilaner, when administered once monthly over eight months at the highest recommended dose and overdoses of three- and five-fold, to 8-week-old healthy kittens, is well tolerated.
洛哌丁胺是一种新型异恶唑啉类药物，用于治疗猫的跳蚤和蜱虫感染。这项使用洛哌丁胺香草酵母味咀嚼片（Credelio，礼蓝）的实验室研究，在 8 周龄健康小猫中，以随机、盲法、平行组设计，调查了起始剂量为最大推荐剂量范围上限的 1 倍（26mg/kg）、3 倍（78mg/kg）和 5 倍（130mg/kg）时的安全性。
在健康小猫中，以每月口服 1 次，连续 8 个月的方式，给予最高推荐剂量，即 1 倍（26mg/kg）和高剂量，即 3 倍（78mg/kg）和 5 倍（130mg/kg），评估洛哌丁胺咀嚼片的安全性。16 只雄性和 16 只雌性健康 8 周龄小猫，平均体重分别为 0.79kg 和 0.75kg，随机分为未治疗对照组或洛哌丁胺组，剂量分别为 26mg/kg（1 倍）、78mg/kg（3 倍）或 130mg/kg（5 倍），每月 1 次，连续 8 个月。对照组给予假处理。所有动物在治疗前 30 分钟内喂食。安全性评估包括一般健康观察、详细临床观察、全面的体格/神经检查，包括眼科检查、心电图（ECG）和临床病理学评估（血液学、临床化学和尿液分析）、食物和水的消耗、体重、药代动力学采血、器官大体和显微镜检查。
除对照组外，所有治疗动物在研究过程中均证实有洛哌丁胺的全身暴露。在每日临床观察、湿粮食物消耗、眼底镜、体格/神经和显微镜检查中，均未观察到与治疗相关的影响。一些临床病理学参数、体重、干粮食物消耗、心电图和器官重量记录到统计学显著差异，但未观察到任何记录的观察结果具有临床相关性。
在 8 周龄健康小猫中，每月口服洛哌丁胺一次，连续 8 个月，最高推荐剂量和 3 倍和 5 倍超剂量，耐受性良好。
