Elanco Animal Health, 2500 Innovation Way, Greenfield, IN 46140, USA.
Parasit Vectors. 2021 May 28;14(1):285. doi: 10.1186/s13071-021-04760-z.
The combination of milbemycin oxime (MO) and lotilaner (Credelio Plus) is a novel systemic endectocide that provides month-long effectiveness in dogs after a single oral treatment. The safety of Credelio Plus flavored chewable tablets was investigated in three target animal safety studies. Two studies (one in juveniles and one in adults) evaluated the long-term safety, and one study evaluated the acute safety of the product when administered orally at the upper end of the recommended dose range (0.75-1.53 mg/kg MO and 20-41 mg/kg lotilaner) and multiples of this dose.
The objectives of these studies were to determine the long-term and acute safety of MO and lotilaner flavored chewable tablets in healthy dogs. All three studies were randomized, blinded, parallel-group design studies in healthy Beagle dogs. In each of the two long-term studies, 32 dogs were randomized among four groups to untreated controls or to treated groups at target doses of 1X, 3X, or 5X. Treatment was administered on seven (adult dogs) or nine (juvenile dogs) occasions with dosing every 4 weeks. In the acute study, 48 dogs were randomized among four groups to untreated controls or to treated groups at 1X, 3X, or 6X. In all three studies, the control group was administered placebo tablets. All dogs were fed 30 to 45 min prior to treatment and the assessment of safety was based on health observations, complete physical/neurological examinations, and food consumption. For the long-term safety studies, safety assessments also included clinical pathology evaluations (hematology, clinical chemistry and urinalysis), body weight, pharmacokinetic blood collections, and macroscopic and microscopic examinations of collected tissues.
MO and lotilaner did not induce any treatment-related adverse effects based on health observations, physical/neurological examinations, or food consumption in the long-term or acute studies. Additionally, in the long-term studies, MO and lotilaner did not induce any treatment-related effects on clinical pathology, body weight, and macroscopic and microscopic examinations.
These three studies demonstrate that Credelio Plus has a wide safety margin when administered at monthly intervals to puppies and dogs at the high end of the commercial dose band.
米尔贝肟（MO）和莫昔克丁（Credelio Plus）联合应用是一种新型的全身性驱虫药，犬单剂量口服后可提供长达一个月的疗效。在三项靶动物安全性研究中对 Credelio Plus 可咀嚼片剂的安全性进行了评估。两项研究（一项在幼犬中进行，一项在成年犬中进行）评估了该产品的长期安全性，另一项研究评估了在推荐剂量范围上限（0.75-1.53mg/kg MO 和 20-41mg/kg 莫昔克丁）和该剂量倍数口服给药时产品的急性安全性。
这些研究的目的是确定 MO 和莫昔克丁可咀嚼片剂在健康犬中的长期和急性安全性。这三项研究均为健康比格犬的随机、双盲、平行组设计研究。在两项长期研究中，32 只犬随机分为 4 组，分别为未处理对照组和靶剂量 1X、3X 或 5X 的处理组。每 4 周给药一次，共给药 7 次（成年犬）或 9 次（幼犬）。在急性研究中，48 只犬随机分为 4 组，分别为未处理对照组和靶剂量 1X、3X 或 6X 的处理组。在所有三项研究中，对照组给予安慰剂片剂。所有犬在给药前 30 至 45 分钟进食，安全性评估基于健康观察、全面的体格/神经学检查和食物消耗。对于长期安全性研究，安全性评估还包括临床病理学评估（血液学、临床化学和尿液分析）、体重、药代动力学血液采集以及收集组织的大体和显微镜检查。
在长期或急性研究中，基于健康观察、体格/神经学检查或食物消耗，MO 和莫昔克丁均未引起任何与治疗相关的不良反应。此外，在长期研究中，MO 和莫昔克丁未引起任何与治疗相关的临床病理学、体重和大体及显微镜检查的影响。
这三项研究表明，Credelio Plus 每月间隔一次给予高剂量范围内的幼犬和犬时，安全性范围很广。
