title: Plasma pharmacokinetic profile of fluralaner (Bravecto™) and ivermectin following concurrent administration to dogs.
abstract: BACKGROUND
  Fluralaner is a novel systemic ectoparasiticide for dogs providing immediate and persistent flea, tick and mite control after a single oral dose. Ivermectin has been used in dogs for heartworm prevention and at off label doses for mite and worm infestations. Ivermectin pharmacokinetics can be influenced by substances affecting the p-glycoprotein transporter, potentially increasing the risk of ivermectin neurotoxicity. This study investigated ivermectin blood plasma pharmacokinetics following concurrent administration with fluralaner.
  
  
  RESULTS
  Ten Beagle dogs each received a single oral administration of either 56 mg fluralaner (Bravecto™), 0.3 mg ivermectin or 56 mg fluralaner plus 0.3 mg ivermectin/kg body weight. Blood plasma samples were collected at multiple post-treatment time points over a 12-week period for fluralaner and ivermectin plasma concentration analysis. Ivermectin blood plasma concentration profile and pharmacokinetic parameters Cmax, tmax, AUC∞ and t½ were similar in dogs administered ivermectin only and in dogs administered ivermectin concurrently with fluralaner, and the same was true for fluralaner pharmacokinetic parameters.
  
  
  CONCLUSIONS
  Concurrent administration of fluralaner and ivermectin does not alter the pharmacokinetics of either compound. Based on the plasma pharmacokinetic profile and the clinical observations, there is no evident interaction between fluralaner and ivermectin, and co-administration does not increase the risk of ivermectin associated neurotoxicity.
authors.affiliation: Merck Animal Health, 2 Giralda Farms, Madison, NJ, USA. feli.walther@merck.com.
authors.forename: Feli M
authors.initials: FM
authors.lastname: Walther
authors.affiliation: MSD Animal Health Innovation GmbH, Zur Propstei, 55270, Schwabenheim, Germany. mark.allan@msd.de.
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Allan
authors.affiliation: MSD Animal Health Innovation GmbH, Zur Propstei, 55270, Schwabenheim, Germany. rainer.roepke@msd.de.
authors.forename: Rainer K A
authors.initials: RK
authors.lastname: Roepke
mesh_terms: D000284:Administration, Oral; D000818:Animals; D019540:Area Under Curve; D004285:Dogs / Q000097:blood*; D004347:Drug Interactions; D006207:Half-Life; D007306:Insecticides / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D007555:Isoxazoles / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D007559:Ivermectin / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*
chemical_list: C000591860:A1443 compound; D007306:Insecticides; D007555:Isoxazoles; D007559:Ivermectin