title: Safety of fluralaner chewable tablets (Bravecto), a novel systemic antiparasitic drug, in dogs after oral administration.
abstract: BACKGROUND
  Fluralaner is a novel systemic insecticide and acaricide that provides long acting efficacy in dogs after a single oral treatment. This study investigated the safety of oral administration of fluralaner in chewable tablets to dogs at the highest recommended treatment dose and at multiples of this dose.
  
  
  METHODS
  Thirty-two (16 male and 16 female) healthy 8-week old Beagle dogs weighing 2.0 - 3.6 kg at first administration were included in the study. Fluralaner was administered on three occasions at 8-week intervals at doses of up to 56, 168, and 280 mg fluralaner/kg body weight, equivalent to 1, 3, and 5 times the highest recommended treatment dose of fluralaner; sham dosed dogs served as controls.During the study, all dogs were clinically observed, and their health was carefully monitored including body weight development, food consumption and measurement of hematology, coagulation, clinical chemistry (including measurement of levels of ACTH and C-reactive protein) and urinalysis. Following euthanasia of the dogs, complete gross post mortem examination, including organ weight determination, and histopathological examination of multiple tissues were conducted.
  
  
  RESULTS
  There were no clinical findings related to fluralaner treatment. Statistically significant differences between the treated groups and the control group were observed for some clinical pathology parameters and organ weights; none of these findings were considered to be of clinical relevance.
  
  
  CONCLUSIONS
  Oral administration of fluralaner at the highest recommended treatment dose (56 mg/kg) at 8-week intervals is well tolerated and has a safety margin of more than five in healthy dogs eight weeks of age or older and weighing at least 2 kg.
authors.affiliation: MSD Animal Health Innovation GmbH, Zur Propstei, Schwabenheim 55270, Germany. feli.walther@msd.de.
authors.forename: Feli M
authors.initials: FM
authors.lastname: Walther
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Allan
authors.forename: Rainer K A
authors.initials: RK
authors.lastname: Roepke
authors.forename: Martin C
authors.initials: MC
authors.lastname: Nuernberger
mesh_terms: D056810:Acaricides / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology; D000284:Administration, Oral; D000818:Animals; D000977:Antiparasitic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D001835:Body Weight / Q000187:drug effects; D002097:C-Reactive Protein / Q000032:analysis; D004285:Dogs / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D004435:Eating / Q000187:drug effects; D005260:Female; D006405:Hematology; D007306:Insecticides / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology; D007555:Isoxazoles / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D008297:Male; D009929:Organ Size / Q000187:drug effects; D012449:Safety; D016037:Single-Blind Method; D013607:Tablets; D013997:Time Factors
chemical_list: C000591860:A1443 compound; D056810:Acaricides; D000977:Antiparasitic Agents; D007306:Insecticides; D007555:Isoxazoles; D013607:Tablets; D002097:C-Reactive Protein