The synergistic action of imidacloprid and flumethrin and their release kinetics from collars applied for ectoparasite control in dogs and cats

Abstract

BackgroundThe 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.MethodsThe 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.ResultsAn 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.ConclusionHere 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.

Repellency Effect of an Imidacloprid / Flumethrin (Seresto®) Controlled Release Polymer Matrix Collar against the Australian Paralysis Tick (Ixodes holocyclus) in Dogs

“…Some of these studies have also presented data demonstrating a repellency effect, employing various protocols. Stanneck et al (2012a) demonstrated the acaricidal efficacy of Seresto ® (100 % for 8 months duration) against the Brown dog tick Rhipicephalus sanguineus after 24 h incubation with hair from treated dogs and cats. Efficacy and repellency against several tick species were shown by Stanneck et al (2012b).…”

“…The Seresto ® collar (Bayer, 10 % imidacloprid, 4.5 % flumethrin), is a polymer matrix collar for dogs and cats that allows a continuous and prolonged release of the active ingredients imidacloprid, a chloronicotinyl compound, and flumethrin, an α-cyanopyrethroid, onto the skin surface and hair coat of treated animals (Stanneck et al 2012a). It has been shown to achieve long-term persistent efficacy of 8 months against fleas (Ctenocephalides felis felis) (Stanneck et al 2012b(Stanneck et al , 2012c) and 4 months against I. holocyclus on dogs (Smith et al 2013).…”

It shouldn’t happen to a dog … or a veterinarian: clinical paradigms for canine vector-borne diseases

“…Failure to apply an ectoparasiticide correctly jeopardises the entire strategy [77]. Breakdown in ectoparasite control programs are thought to occur frequently, and poor owner compliance is an important reason for this [78]. Use of the incorrect frequency of application or dose of the product through misunderstanding or oversight is common, risking ectoparasite attachment, feeding and pathogen transmission [78].…”

“…Breakdown in ectoparasite control programs are thought to occur frequently, and poor owner compliance is an important reason for this [78]. Use of the incorrect frequency of application or dose of the product through misunderstanding or oversight is common, risking ectoparasite attachment, feeding and pathogen transmission [78]. Application of the product by the wrong route, such as inadvertent oral administration of a spot-on product has been recorded [79].…”

Long-Term Efficacy of an Imidacloprid 10 % / Flumethrin 4.5 % Polymer Matrix Collar (Seresto®, Bayer) against the Australian Paralysis Tick (Ixodes holocyclus) in Dogs

“…Currently available options for the control of I. holocyclus on dogs are limited and include topically applied spot-ons or sprays containing permethrin or fipronil that require fortnightly reapplication, or collars containing flumethrin, amitraz or deltamethrin that give protection for 6 weeks to 3 months. Seresto ® (Bayer; Investigational Veterinary Product (IVP)) contains imidacloprid (10 %), an insecticide from the chloronicotinyl group of compounds, and flumethrin (4.5 %), an ectoparasiticide belonging to the α-cyano-pyrethroids, in a novel polymer matrix collar that allows for their slow and continuous release onto the skin surface and hair coat of a treated animal (Stanneck et al 2012a). The IVP is registered for use on dogs and cats in many countries including in the European Union, the United Kingdom, the United States of America and New Zealand.…”