title: The synergistic action of imidacloprid and flumethrin and their release kinetics from collars applied for ectoparasite control in dogs and cats.
abstract: BACKGROUND
  The control of tick and flea burdens in dogs and cats has become essential to the control of important and emerging vector borne diseases, some of which are zoonoses. Flea worry and flea bite hypersensitivity are additionally a significant disease entity in dogs and cats. Owner compliance in maintaining the pressure of control measures has been shown to be poor. For these reasons efforts are continuously being made to develop ectoparasiticides and application methods that are safe, effective and easy to apply for pet owners. A new polymer matrix collar has recently been developed which is registered for 8 months use in cats and dogs. The basic properties of this collar have been investigated in several in vitro and in vivo studies.
  
  
  METHODS
  The effects of imidacloprid, flumethrin and the combination were evaluated in vitro by means of whole cell voltage clamp measurement experiments conducted on isolated neuron cells from Spodoptera frugiperda. The in vitro efficacy of the two compounds and the combination against three species of ticks and their life stages and fleas were evaluated in a dry surface glass vial assay. The kinetics of the compounds over time in the collar were evaluated by the change in mass of the collar and measurement of the surface concentrations and concentrations of the actives in the collar matrix by HPLC. Hair clipped from collar treated dogs and cats, collected at various time points, was used to assess the acaricidal efficacy of the actives ex vivo.
  
  
  RESULTS
  An in vitro isolated insect nerve model demonstrated the synergistic neurotoxic effects of the pyrethroid flumethrin and the neonicotinoid imidacloprid. An in vitro glass vial efficacy and mortality study against various life stages of the ticks Ixodes ricinus, Rhipicephalus sanguineus and Dermacentor reticulatus and against the flea (Ctenocephalides felis) demonstrated that the combination of these products was highly effective against these parasites. The release kinetics of these actives from a neck collar (compounded with 10% imidacloprid and 4.5% flumethrin) was extensively studied in dogs and cats under laboratory and field conditions. Acaricidal concentrations of the actives were found to be consistently released from the collar matrix for 8 months. None of the collar studies in dogs or cats were associated with any significant collar related adverse event.
  
  
  CONCLUSIONS
  Here we demonstrated the synergism between the pyrethroid flumethrin and the neonicotinoid imidacloprid, both provided in therapeutically relevant doses by a slow release collar matrix system over 8 months. This collar is therefore a convenient and safe tool for a long-term protection against ectoparasites.
authors.affiliation: Bayer Animal Health GmbH, Leverkusen, Germany. dorothee.stanneck@bayer.com
authors.forename: Dorothee
authors.initials: D
authors.lastname: Stanneck
authors.forename: Ulrich
authors.initials: U
authors.lastname: Ebbinghaus-Kintscher
authors.forename: Eva
authors.initials: E
authors.lastname: Schoenhense
authors.forename: Eva M
authors.initials: EM
authors.lastname: Kruedewagen
authors.forename: Andreas
authors.initials: A
authors.lastname: Turberg
authors.forename: Andrew
authors.initials: A
authors.lastname: Leisewitz
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Jiritschka
authors.forename: Klemens J
authors.initials: KJ
authors.lastname: Krieger
mesh_terms: D000818:Animals; D002371:Cat Diseases / Q000517:prevention & control; D002415:Cats; D004283:Dog Diseases / Q000517:prevention & control; D004285:Dogs; D016503:Drug Delivery Systems; D004357:Drug Synergism; D004478:Ectoparasitic Infestations / Q000517:prevention & control / Q000662:veterinary; D005260:Female; D007093:Imidazoles / Q000493:pharmacokinetics / Q000494:pharmacology*; D007306:Insecticides / Q000493:pharmacokinetics / Q000494:pharmacology; D008297:Male; D000073943:Neonicotinoids; D009574:Nitro Compounds / Q000493:pharmacokinetics / Q000494:pharmacology*; D011722:Pyrethrins / Q000493:pharmacokinetics / Q000494:pharmacology*; D005423:Siphonaptera / Q000187:drug effects*; D013987:Ticks / Q000187:drug effects*
chemical_list: D007093:Imidazoles; D007306:Insecticides; D000073943:Neonicotinoids; D009574:Nitro Compounds; D011722:Pyrethrins; C041392:flumethrin; C082359:imidacloprid