Elanco Animal Health, Schwarzwaldallee 215, WRO-1032.2.52, CH-4058, Basel, Switzerland.
Elanco Animal Health, 2500 Innovation Way, Greenfield, IN, 46140, USA.
Parasit Vectors. 2017 Nov 1;10(1):538. doi: 10.1186/s13071-017-2468-y.
Lotilaner (Credelio™, Elanco) is a novel isoxazoline that provides rapid speed of flea and tick knockdown which is sustained for at least 1 month following oral administration to dogs. The safety of lotilaner flavoured chewable tablets was investigated in a randomized, blinded, parallel-group design study in healthy Beagle puppies starting at 8 weeks of age. Lotilaner was administered orally once a month over 8 months at one, three and five times the upper level of the recommended dose range (of 20 to 43 mg/kg).
The objective of this study was to determine the safety of lotilaner flavoured chewable tablets in healthy dogs when administered monthly over an extended time period at the highest recommended dose rate, i.e. 1× and at elevated dose rates, i.e. 3× and 5×. Sixteen male and 16 female healthy 8-week-old puppies, weighing ~1.5 to 3.0 kg, were randomized among four groups to be untreated controls or to receive lotilaner at dose rates of 43 mg/kg (1×), 129 mg/kg (3×), or 215 mg/kg (5×) on eight occasions - every 4 weeks over 8 months. The control group was sham-dosed. Study dogs were fed within 30 min prior to treatment. Assessment of safety was based on general health observations, detailed clinical observations, complete physical/neurological examinations, including ophthalmological examinations and clinical pathology evaluations (haematology, clinical chemistry and urinalysis), food and water consumption, body weight, pharmacokinetic blood collections, macroscopic and microscopic examinations.
Blood concentrations of lotilaner confirmed systemic exposure of all study dogs with the exception of the control group. Lotilaner did not induce any treatment-related effects on body weight, food consumption, opthalmoscopic, physical/neurological and electrocardiographic examinations. For clinical pathology, no changes related to treatment were noted. There were no treatment-related changes in gross examinations. After microscopic examinations, minor findings recorded in kidneys were of no toxicological relevance. Changes in the reproductive tissues were attributed to the peri-pubertal age and growth of the animals.
Lotilaner was well-tolerated in healthy puppies at 8 week of age when administered once monthly on eight occasion over 8 months at the highest recommended dose and at three and five-fold overdose.
洛特林纳（Credelio ™，礼蓝）是一种新型的异恶唑啉，可迅速杀灭跳蚤和蜱虫，口服后至少持续 1 个月。在 8 周龄健康比格犬中进行的一项随机、双盲、平行分组设计研究中，评估了洛特林纳调味咀嚼片的安全性。洛特林纳每月口服一次，8 个月内以推荐剂量范围（20 至 43mg/kg）的 1 倍、3 倍和 5 倍进行给药。16 只雄性和 16 只雌性健康的 8 周龄幼犬，体重约 1.5 至 3.0kg，随机分为 4 组，分别为未处理的对照组或接受洛特林纳 43mg/kg（1 倍）、129mg/kg（3 倍）或 215mg/kg（5 倍）的剂量，共 8 次，每 4 周一次，8 个月。对照组进行假处理。研究犬在治疗前 30 分钟内进食。安全性评估基于一般健康观察、详细临床观察、全面的体格/神经学检查，包括眼科检查和临床病理学评估（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、肉眼和显微镜检查。
除对照组外，所有研究犬的血药浓度均证实了洛特林纳的全身暴露。洛特林纳未引起体重、食物消耗、眼科、体格/神经学和心电图检查的任何与治疗相关的影响。临床病理学方面，未观察到与治疗相关的变化。大体检查未见与治疗相关的变化。显微镜检查后，肾脏的轻微发现与毒性无关。生殖组织的变化归因于动物的围青春期年龄和生长。
当 8 周龄健康幼犬在 8 个月内每月口服一次，8 次，以推荐剂量的 1 倍和 3 倍、5 倍超剂量给药时，洛特林纳耐受性良好。
