title: Determination of the effective dose of a novel oral formulation of sarolaner (Simparica™) for the treatment and month-long control of fleas and ticks on dogs.
abstract: Three laboratory studies were conducted to determine the appropriate dose of sarolaner, a novel isoxazoline, for the treatment and month-long control of infestations of fleas and ticks on dogs. In the first study, dogs were treated orally with sarolaner suspension formulations at 1.25, 2.5 or 5.0mg/kg, and infested with Dermacentor reticulatus, Rhipicephalus sanguineus ticks and with Ctenocephalides felis felis (cat flea) prior to treatment and then weekly for up to 8 weeks. Fleas and ticks were counted 48h after treatment and after each subsequent infestation at 24h for fleas and 48h for ticks. The lowest dose of sarolaner (1.25mg/kg) provided 100% efficacy against fleas from treatment through Day 35 and 98.4% at Day 56. This dose of sarolaner resulted in 99.7-100% control of both species of ticks through Day 28. In Study 2, dogs were dosed orally with placebo or sarolaner suspension formulations at 0.625, 1.25 or 2.5mg/kg and infested with Ixodes scapularis prior to treatment and weekly for 6 weeks, Amblyomma americanum (pretreatment and Day 26), Dermacentor variabilis (Day 33) and A. maculatum (Day 41). Ixodes scapularis was the most susceptible; the lowest dose (0.625mg/kg) providing>95% efficacy through Day 43. Efficacy against D. variabilis on Day 35 was>95% at 1.25 and 2.5mg/kg, whereas the 0.625mg/kg dose gave only 61.4% efficacy. Amblyomma spp. were the least susceptible ticks; efficacy of the 1.25mg/kg dose at Day 28 for A. americanum was markedly lower (88.5%) than achieved for D. reticulatus (100%) at Day 28 and also lower than for D. variabilis at Day 35 (96.2%). In Study 3, dogs were dosed orally with placebo or sarolaner in the proposed commercial tablet (Simparica™) at 1.0, 2.0 or 4.0mg/kg, and infested with A. maculatum, one of the ticks determined to be dose limiting, prior to treatment and then weekly for 5 weeks. All doses gave 100% control of the existing infestation. The two highest dosages resulted in >93% control of subsequent challenges for 5 weeks. There was no significant improvement in efficacy provided by the 4.0 mg/kg dose over the 2.0mg/kg dose (P>0.05) at any time point. The 2.0mg/kg dose was superior to the 1.0mg/kg on Day 14 (P=0.0086) and as efficacy for 1.0mg/kg declined below 90% at Day 28, a single 1mg/kg dose would not provide a full month of tick control. Thus, 2.0mg/kg was selected as the sarolaner dose rate to provide flea and tick control for at least one month following a single oral treatment.
authors.affiliation: Zoetis, Veterinary Medicine Research and Development, 333 Portage St. Kalamazoo, MI 49007, USA.
authors.forename: Tom L
authors.initials: TL
authors.lastname: McTier
authors.affiliation: Zoetis, Veterinary Medicine Research and Development, 333 Portage St. Kalamazoo, MI 49007, USA.
authors.forename: Robert H
authors.initials: RH
authors.lastname: Six
authors.affiliation: ClinVet International (pty) Ltd., Uitsigweg, Bainsvlei 9338, Bloemfontein, South Africa.
authors.forename: Josephus J
authors.initials: JJ
authors.lastname: Fourie
authors.affiliation: Zoetis, Veterinary Medicine Research and Development, 333 Portage St. Kalamazoo, MI 49007, USA.
authors.forename: Aleah
authors.initials: A
authors.lastname: Pullins
authors.affiliation: Zoetis, Veterinary Medicine Research and Development, 333 Portage St. Kalamazoo, MI 49007, USA.
authors.forename: Laura
authors.initials: L
authors.lastname: Hedges
authors.affiliation: Zoetis, Veterinary Medicine Research and Development, 333 Portage St. Kalamazoo, MI 49007, USA.
authors.forename: Sean P
authors.initials: SP
authors.lastname: Mahabir
authors.affiliation: Zoetis, Veterinary Medicine Research and Development, 333 Portage St. Kalamazoo, MI 49007, USA. Electronic address: tom.mctier@Zoetis.com.
authors.forename: Melanie R
authors.initials: MR
authors.lastname: Myers
mesh_terms: D000284:Administration, Oral; D000818:Animals; D004283:Dog Diseases / Q000188:drug therapy* / Q000517:prevention & control*; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004478:Ectoparasitic Infestations / Q000517:prevention & control / Q000662:veterinary*; D007306:Insecticides / Q000008:administration & dosage; D007555:Isoxazoles / Q000008:administration & dosage; D005423:Siphonaptera; D013987:Ticks; D016896:Treatment Outcome
chemical_list: D007306:Insecticides; D007555:Isoxazoles
keywords: Amblyomma maculatum; Ctenocephalides felis felis; Dog; Flea; Isoxazoline; Prevention; Sarolaner; Tick; Treatment