Acaricidal efficacy of a new combination of fipronil and permethrin against Ixodes ricinus and Rhipicephalus sanguineus ticks.

BACKGROUND: Two blinded, controlled laboratory studies were conducted to assess the acaricidal efficacy of a new combination of fipronil and permethrin (Frontline Tri-Act/Frontect) against two tick species. Study A evaluated the efficacy of the product against both Ixodes ricinus and Rhipicephalus sanguineus and Study B evaluated the efficacy against R. sanguineus only. METHODS: 16 (Study A) and 12 (Study B) healthy adult dogs were allocated to two groups in each study. Dogs in Group 1 served as untreated controls. Dogs in Group 2 were treated with a new topical spot-on formulation containing 6.76% (w/v) fipronil + 50.48% (w/v) permethrin once on Day 0. Each dog of study A was infested with 50 unfed adult ticks of each species and each dog of study B was infested with 50 unfed adult Rhipicephalus sanguineus prior to treatment (Day -2 in Study A, Day -1 in Study B) and post treatment on Days 7, 14, 21 and 28. The ticks were removed and counted 48 h after treatment (Day 2) or subsequent infestations (Days 9, 16, 23 and 30). Acaricidal efficacy was defined as the percent reduction in the number of live ticks in the treated group compared to the untreated control group. RESULTS: The percent efficacy in the treated group for R. sanguineus was 100%, 100%, 100%, 100% and 96.7% in Study A, and 94.4%, 100%, 100%, 98.7% and 98.0% in Study B, for counts performed on Days 2, 9, 16, 23 and 30, respectively. For I. ricinus, in Study A, the percent efficacy of the treatment was 100%, 100%, 100%, 100% and 99.2% for counts performed on Days 2, 9, 16, 23 and 30, respectively. There was a significant difference of the geometric mean numbers of live ticks between the treated and control groups at each time point in each study (p = 0.005 for every day in Study A, and p < 0.005 for every day in Study B). CONCLUSIONS: A single topical administration of a combination of fipronil and permethrin provides excellent acaricidal efficacy against both I. ricinus and R. sanguineus for at least 4 weeks.

Efficacy of a new combination of fipronil and permethrin against Ctenocephalides felis flea infestation in dogs.

BACKGROUND: Five studies were conducted to evaluate the effect of a new combination of fipronil and permethrin on cat fleas, Ctenocephalides felis, when applied to dogs, including dogs that underwent water exposure or shampooing. METHODS: In each study, 16 dogs were allocated to two groups. Each dog was infested with 100 unfed adult fleas on Days -1, 7, 14, 21 and 28. Eight dogs were treated with a new topical spot-on formulation containing 6.76% w/v fipronil + 50.48% w/v permethrinon Day 0; and eight dogs served as untreated controls. Twenty-four or 48 h after treatment or subsequent infestation, each dog was combed to remove and count live fleas. In addition, the dogs were subjected to different levels of water or shampoo exposure. In study 1, dogs were not subjected to any water exposure or shampooing; in study 2, dogs were water immersed twice during the month on Days 10 and 24; in study 3, dogs were water immersed three times on Days 10, 17 and 24; and in studies 4 and 5, dogs were shampooed once on Day 17. RESULTS: All groups of dogs administered a single topical treatment with a combination of fipronil and permethrin had significantly (p < 0.005) lower flea counts than untreated controls 24 h and 48 h post-treatment or post-infestation, regardless of whether they underwent water exposure/shampooing or not. The reductions in C. felis counts were between 98.4% and 100% at all time points in all studies. CONCLUSIONS: The new topical spot-on formulation of fipronil and permethrin maintains a high level of protection of dogs against C. felis flea infestations even when the dogs are exposed to environmental factors that are believed to adversely affect efficacy, such as water exposure or shampooing.

Assessment of the onset of action of afoxolaner against existing adult flea (Ctenocephalides felis) infestations on dogs.

The speed of kill of afoxolaner against experimental infestations by Ctenocephalides felis was evaluated after oral administration of afoxolaner in a soft chew (NEXGARD(®)) at a dose to achieve 2.5mg/kg bodyweight. Forty beagles were allocated to two treatment groups. Dogs in Treatment Group 1 were untreated controls. Dogs in Treatment Group 2 were treated on Day-0 with afoxolaner, according to their pre-treatment bodyweight. All dogs were infested with approximately 100 C. felis on Day-1. Live fleas were counted upon removal at 5 time points after treatment (i.e., 2, 4, 8, 12 and 24h after treatment). For each time point, counts were performed on 4 dogs from each of the treated and the untreated groups. Early curative flea killing efficacy was evaluated with respect to the untreated control group. The afoxolaner treated group had significantly fewer fleas than the untreated control group at 8, 12, and 24h (p<0.001). The percent efficacies of orally administered afoxolaner were 15.0%, 87.8%, 99.5%, 100.0%, and 100.0% at 2, 4, 8, 12, and 24h, respectively. In this study, afoxolaner began killing fleas by 2h after treatment with increasing efficacy at subsequent time points and had >99.5% efficacy at 8, 12, and 24h after treatment demonstrating an early onset of action.

Evaluation of the curative and preventive efficacy of a single oral administration of afoxolaner against cat flea Ctenocephalides felis infestations on dogs.

The efficacy of orally administered afoxolaner for treatment and prevention of repeated infestations with adult Ctenocephalides felis on dogs was evaluated in two studies after administration of a beef-flavored soft chew. In each study, 32 dogs were divided randomly into four equal groups. Dogs in Groups 1 and 3 were not treated and served as controls. Dogs in Groups 2 and 4 were treated on Day 0 with a combination of chewable tablets to be as close as possible to the minimum therapeutic dose of 2.5mg/kg. All animals were infested experimentally with unfed C. felis (100 ± 5) on Days -1, 7, 14, 21, 28 and 35. Flea killing efficacy was evaluated in both studies while, efficacy against flea egg production was assessed in Study 1. Live fleas were counted at 12 (Groups 1 and 2) and 24h (Groups 3 and 4), after treatment or after weekly infestations. In Study 1, flea eggs were collected and counted at either 12 or 24h after each flea infestation on Days 7, 14, 21, 28 and 35. The results of both studies demonstrate the long lasting and rapid efficacy of afoxolaner against C. felis, when administered as a single oral dose to dogs. For flea counts conducted 24h after treatment or infestation, efficacy was 100% for all time points up to Day 36 in both studies, except for one time point (99.9% on Day 22) for Study 2. For flea counts performed 12h after treatment or infestation, efficacy was ≥ 95.2% until Day 21 in both studies. Efficacy at 12h was ≥ 93.0% on Day 35 in Study 1 and ≥ 89.7% on Day 35 in Study 2. The treated groups had significantly fewer fleas than untreated control dogs in both studies for all flea counts (p=0.003 Study 1, p=0.0006 Study 2). In Study 1, for all egg counts performed at or beyond Day 7, efficacy in egg reduction was >99% for all time points between Days 7 and 35.

Evaluation of the efficacy of afoxolaner against two European dog tick species: Dermacentor reticulatus and Ixodes ricinus.

The acaricidal efficacy of a novel oral formulation of afoxolaner (NEXGARD(®), Merial) against two European tick species was assessed in dogs experimentally infested with Ixodes ricinus and Dermacentor reticulatus. Three studies, each characterized by a negative controlled randomized block design, were conducted with a total of 52 beagle or mongrel dogs of both sexes. Starting 2 days before treatment, each dog was infested weekly with approximately 50 ticks. The number of live ticks was counted at 48 h post-treatment (Day 2) as well as 48 h following each infestation on Days 9, 16, 23, and 30. Afoxolaner, administered at an average dose of 2.7 mg/kg bodyweight (range 2.5-2.9 mg/kg), rapidly eliminated the pre-existing tick infestations with over 99% acaricidal efficacy and controlled the weekly re-infestations for up to 30 days post treatment with over 96% efficacy on both tick species. Afoxolaner provides excellent acaricidal efficacy against these two major European tick species using the oral route of administration.

Efficacy of afoxolaner against Dermacentor variabilis ticks in dogs.

Efficacy of afoxolaner, a novel isoxazoline insecticide/acaricide, against Dermacentor variabilis ticks was confirmed in two laboratory studies. Each study utilized a controlled, randomized block design. One day prior to treatment, beagle dogs were infested with 50 unfed adult ticks. Repeat infestations were performed weekly for four weeks. The number of live ticks remaining on each dog was determined 48 h after treatment and after each subsequent infestation. A single oral treatment with a dose approaching the minimum effective dose of afoxolaner (2.5mg/kg) eliminated the pre-existing infestations by D. variabilis ticks and controlled weekly re-infestations with 99.7-100% efficacy up to Day 23 and >97% efficacy at Day 30.

Evaluation of the efficacy of afoxolaner against Haemaphysalis longicornis on dogs.

A controlled study to assess the acaricidal efficacy of afoxolaner in dogs after a single oral administration was conducted against Haemaphysalis longicornis ticks. The study was characterized by a negative controlled randomized block design and included sixteen beagle dogs of both sexes. Starting two days before treatment, each dog was infested weekly with 50 ticks over 4 weeks. The number of live ticks was determined 48 h after treatment and then 48 h after each infestation. The mean dose of afoxolaner received by dogs was 3.0mg/kg (range: 2.5-3.1mg/kg). Afoxolaner rapidly eliminated pre-existing tick infestations (100% ticks killed within 48 h of treatment) and controlled weekly re-infestations (91.9% prophylactic efficacy at Day 30).

Curative and preventive efficacy of orally administered afoxolaner against Ctenocephalides canis infestation in dogs.

The efficacy of orally administered afoxolaner against adult dog fleas, Ctenocephalides canis, was evaluated in a controlled, blinded study. A total of 32 dogs were infested with 100 adult unfed fleas approximately 24h prior to treatment and then at weekly intervals for 5 weeks after treatment. Live fleas were counted upon removal at 12h (for 16 dogs) and 24h (for the remaining 16 dogs) after treatment (for counts performed the first week) or after infestation (for counts performed on subsequent weeks). In addition, flea eggs were collected from each pen and counted for the dogs with flea removal at 24h. Dosing of individual dogs was achieved using a combination of the chewable tablets to be as close as possible to the minimum effective dose of 2.5mg/kg. The percent efficacy of the afoxolaner treatment was ≥ 99.0% for all 24-h flea counts. For flea counts performed 12h after treatment or infestations, the percent efficacy was ≥ 94.1% up to Day 21. After Day 1, no flea eggs were recovered from the afoxolaner treated group, providing 100% reduction in numbers of flea eggs recovered versus untreated control group. This study confirmed that a single oral treatment with afoxolaner provided excellent efficacy against infestations by C. canis within 12-24h after treatment, prevented re-infestations, and completely prevented egg production from new flea infestations for up to 5 weeks.