BackgroundLotilaner (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).MethodsThe 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.ResultsBlood 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.ConclusionsLotilaner 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.Electronic supplementary materialThe online version of this article (10.1186/s13071-017-2468-y) contains supplementary material, which is available to authorized users.

The aim of this study was to determine whether epiregulin, a novel member of EGF-related growth factor family, was able to affect proliferation and secretory function of rat insulinoma INS-1E and RINm5F cell lines. A 24 h treatment with epiregulin resulted in a stimulation of INS-1E and RINm5F cells proliferation; this effect was completely blocked in the presence of an anti-epiregulin antibody which did not affect basal DNA synthesis in the absence of added ligand. In acute experiments, epiregulin was able to potentiate insulin release in the presence of glucose or arginine, in the two cell lines. Finally, in the two cell lines expressing ErbB receptors, we demonstrated that only EGFR/ErbB1 was activated by epiregulin. Thus, epiregulin appears as a new growth and insulinotropic factor in pancreatic beta cell lines.

BackgroundLotilaner 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 (CredelioTM, 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).MethodsThe 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.ResultsSystemic 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.ConclusionsLotilaner, 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.Electronic supplementary materialThe online version of this article (10.1186/s13071-018-2969-3) contains supplementary material, which is available to authorized users.

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