Preventive efficacy of four or six monthly oral doses of 24 µg/kg moxidectin compared to six monthly doses of Heartgard® Plus or Interceptor® Plus against macrocyclic lactone-resistant heartworm (Dirofilaria immitis) strains in dogs.

BACKGROUND: Recent reports indicated that increasing the monthly oral dosage and the number of consecutive monthly doses of moxidectin improved the efficacy against macrocyclic lactone (ML)-resistant Dirofilaria immitis. The two laboratory studies reported here evaluated the efficacy of four or six monthly oral doses of 24 µg/kg moxidectin compared to six monthly doses of either Heartgard® Plus (ivermectin/pyrantel) or Interceptor® Plus (milbemycin oxime/praziquantel) against ML-resistant D. immitis strains. METHODS: Dogs were inoculated 30 days prior to first treatment with 50 third-stage (L3) larvae of a ML-resistant strain of D. immitis, ZoeLA or JYD-34. In each study, dogs (six per group) were randomized to treatment with six monthly doses of placebo, four or six monthly doses of 24 µg/kg moxidectin, or six monthly doses of Heartgard® Plus or Interceptor® Plus at their label dose rates. Efficacy was evaluated by adult heartworm counts approximately nine months after L3 inoculation. RESULTS: All negative-control dogs were infected with adult heartworms (geometric mean, 35.6; range, 24-41) for ZoeLA and (geometric mean, 32.9; range, 30-37) for JYD-34. Efficacies against ZoeLA for moxidectin, Heartgard® Plus and Interceptor® Plus were ≥ 96.1%, 18.7% and 21.2%, respectively. Adult counts for both moxidectin-treated groups were significantly lower than negative control (P < 0.0001), significantly lower than Heartgard® Plus and Interceptor® Plus (P < 0.0001), but not significantly different from each other (P = 0.5876). Counts for Heartgard® Plus and Interceptor® Plus were not significantly different than negative control (P ≥ 0.2471). Efficacies against JYD-34 were ≥ 95.9%, 63.9% and 54.6% for moxidectin, Heartgard® Plus and Interceptor® Plus, respectively. Counts for all groups were significantly lower than negative control (P ≤ 0.0001). Counts for six monthly doses of moxidectin were significantly lower than those for four monthly doses (P = 0.0470), and the counts for both moxidectin-treated groups were significantly lower than Heartgard® Plus and Interceptor® Plus (P ≤ 0.0002). CONCLUSIONS: Moxidectin administered orally at 24 µg/kg to dogs for four or six consecutive months was ≥ 95.9% effective in preventing the development of two ML-resistant heartworm strains and resulted in significantly fewer adult D. immitis than in dogs treated with Heartgard® Plus or Interceptor® Plus when administered for six consecutive months at their approved label dosages in two laboratory efficacy studies.

Laboratory studies evaluating the efficacy of a novel orally administered combination product containing sarolaner, moxidectin and pyrantel (Simparica Trio™) for the treatment and control of flea infestations on dogs.

BACKGROUND: Five studies were conducted to evaluate a novel oral combination tablet containing sarolaner, moxidectin and pyrantel (Simparica Trio™), for efficacy against induced flea infestations, speed of kill and effects on flea reproduction on dogs. METHODS: Based on pre-treatment flea counts, dogs were randomly allocated to treatment with a single, oral dose of either placebo or Simparica Trio™ at the minimum label dose of 1.2 mg/kg sarolaner, 24 µg/kg moxidectin and 5 mg/kg pyrantel (as pamoate salt) on Day 0. All dogs were infested with approximately 100 unfed, adult fleas (C. felis or C. canis) prior to treatment and weekly for 5 weeks post-treatment. In Studies 1, 2 and 3, the number of viable fleas were comb-counted at 24 h after treatment and after each weekly infestation; Study 2 also included groups treated with tablets containing sarolaner-alone (1.2 mg/kg), moxidectin-alone (24 µg/kg) or pyrantel-alone (5 mg/kg). In Study 4, flea counts were conducted at 3, 4, 8 and 12 h after treatment and subsequent weekly infestations to establish speed of kill. In Study 5 (flea reproduction), dogs were housed in an enclosure designed to facilitate collection of flea eggs. RESULTS: Efficacy of Simparica Trio™ against C. felis was ≥ 99.7% and against C. canis was 100% at 24 h after treatment and after subsequent infestations for at least 35 days. Treatment with sarolaner-alone had similar efficacy to Simparica Trio™, while moxidectin-alone and pyrantel-alone were no different from placebo at most time points. In Study 4, significant flea killing started at 4 h after treatment; by 8 h after treatment, all treated dogs were free of fleas. Following weekly re-infestation, the combination product reduced fleas by ≥ 97.8% within 12 h for 28 days. Simparica Trio™ reduced flea egg-laying by 100% for 35 days. No treatment-related adverse reactions occurred in any study. CONCLUSIONS: A single dose of Simparica Trio™ at the recommended minimum dose provided highly efficacious and rapid treatment within 4 h of existing flea infestations and persistent control of fleas on dogs for 5 weeks. The efficacy against fleas resulted in 100% prevention of flea reproduction for over a month following a single oral dose.

Efficacy of a novel orally administered combination product containing sarolaner, moxidectin and pyrantel (Simparica Trio™) against induced infestations of five common tick species infesting dogs in the USA.

BACKGROUND: The efficacy of a novel oral combination product, Simparica Trio™, containing sarolaner, moxidectin and pyrantel was evaluated against five tick species that commonly infest dogs in the USA, Amblyomma americanum, Amblyomma maculatum, Dermacentor variabilis, Ixodes scapularis and Rhipicephalus sanguineus. METHODS: Laboratory studies were conducted against two different strains of each tick species. In each study, 10 purpose-bred Beagle or mixed-breed dogs were randomly allocated to one of two treatment groups based on pre-treatment host-suitability tick counts. Dogs were infested with approximately 50 (45-55) unfed adult ticks on Days -2, 5, 12, 19, 26 and 33. On Day 0, dogs received either a single oral dose of Simparica Trio™ at the minimum label dose of 1.2 mg/kg sarolaner, 24 µg/kg moxidectin and 5 mg/kg pyrantel (as pamoate salt) or placebo. Tick counts were conducted at 48 h post-treatment and after each subsequent weekly re-infestation for A. maculatum, D. variabilis, I. scapularis and R. sanguineus studies and at 48 hours or at 72 h post-treatment and after weekly re-infestation in the first and second A. americanum studies, respectively. RESULTS: No treatment-related adverse reactions occurred in any study. In all studies, placebo-treated dogs maintained infestations throughout the entire study duration, and dogs treated with Simparica Trio™ had significantly lower (P ≤ 0.0010) mean live tick counts than placebo-treated dogs at all time-points. Against A. maculatum, D. variabilis, I. scapularis and R. sanguineus, a single oral dose of Simparica Trio™ evaluated at 48 h post-treatment provided ≥ 98.9% efficacy against existing infestations, and within 48 h of re-infestation efficacy was ≥ 90.4% through at least Day 28 (except for R. sanguineus on Day 14 in a single study with an efficacy of 89.7%). Against A. americanum, Simparica Trio™ provided ≥ 99.4% efficacy at ≤ 72 h after treatment of existing infestations and maintained ≥ 98.4% efficacy at ≤ 72 h after re-infestation through at least Day 35. CONCLUSIONS: A single dose of Simparica Trio™ administered orally at the minimum label dosage of 1.2 mg/kg sarolaner, 24 µg/kg moxidectin and 5 mg/kg pyrantel provided treatment and control of the common tick species infesting dogs in the USA for at least one month.

Efficacy of a new topical formulation containing selamectin plus sarolaner against three common tick species infesting cats in the United States.

The efficacy of a single topical application of a combination product containing selamectin and sarolaner (selamectin/sarolaner; Revolution® Plus/Stronghold® Plus) was evaluated in seven laboratory studies against Ixodes scapularis (three studies), Dermacentor variabilis (two studies), or Amblyomma maculatum (two studies). In each study, cats were randomly allocated to treatment groups based on pre-treatment host-suitability tick counts. On Days -2, 5, 12, 19, 26 and 33, the cats were infested with unfed adult ticks. On Day 0, cats were treated with either a placebo (vehicle control) or with the spot-on solution at the minimum dose of 6.0 mg selamectin and 1.0 mg sarolaner/kg bodyweight. In one study with I. scapularis and one with D. variabilis an additional group of cats was treated with selamectin alone (Revolution®, Zoetis) at 6.0 mg/kg bodyweight. Tick counts were conducted after treatment and after each weekly re-infestation and efficacy determined relative to placebo-treated animals. There were no treatment-related adverse reactions in any of the studies. Geometric mean live tick counts were significantly (P < 0.05) lower in the selamectin/sarolaner-treated groups compared to the geometric mean tick counts in the placebo-treated groups at all time-points in all studies. For all species, a single topical administration of the selamectin/sarolaner combination resulted in>90% efficacy against existing infestations based on geometric means. Efficacy against weekly re-infestations was >90% based on geometric means for at least 5 weeks for I. scapularis and D. variabilis, and for at least 4 weeks against A. maculatum. Selamectin alone had no efficacy against I. scapularis, where counts on selamectin-treated cats were not significantly different from placebo at all time points (P > 0.05), and for D. variabilis, counts were not significantly different from placebo at 2, 3 and 5 weeks after treatment (P > 0.05) and efficacy was never greater than 85%. Thus, the activity of the sarolaner against three common tick species found on cats in the US is complementary to the existing broad-spectrum parasite control of selamectin. The inclusion of sarolaner with selamectin in a combination product (Revolution® Plus/Stronghold® Plus) provides for the treatment of existing tick infestations and gives at least one month of control against re-infestation following a single topical application.

The speed of kill of a topical combination of selamectin plus sarolaner against induced infestations of Ixodes scapularis ticks on cats.

The speed of kill of a novel, topical product containing selamectin in combination with sarolaner (selamectin/sarolaner; Revolution® Plus/Stronghold® Plus) was evaluated against Ixodes scapularis ticks on cats. Sixteen cats were randomly allocated to a treatment group and treated topically on Day 0 with either placebo (vehicle control) or 6 mg/kg selamectin plus 1 mg/kg sarolaner. Cats were infested with approximately 50 unfed viable adult I. scapularis ticks on Days -2, 7, 14, 21, 28 and 35. Efficacy was assessed at 4, 8, 12, 24, 48 and 72 h after treatment on Day 0 and at 4, 8, 12 and 24 h after post-treatment re-infestations. There were no adverse reactions to the topical treatment with selamectin/sarolaner. Placebo-treated cats maintained tick infestations throughout the study. Treatment with selamectin/sarolaner significantly reduced tick counts within 12 h (P < 0.0001) and resulted in 100% efficacy by 24 h. For subsequent re-infestations, live tick counts were significantly reduced by 12 h after infestation on Day 7 (P = 0.0120) and by 24 h for Days 14-35 (P < 0.0001). At 24 h after the post-treatment re-infestations, efficacy based on geometric (arithmetic) means was ≥96.1% (94.5%) through Day 21, 75.3% (67.7%) on Day 28 and 66.4% (56.4%) on Day 35. Thus, a single topical dose of Revolution® Plus/Stronghold® Plus at the recommended minimum dose started killing ticks within 12-24 hours after treatment and re-infestations for up to 5 weeks. High acaricidal efficacy (≥90% reduction in tick burden) was achieved within 24 h after treatment and subsequent re-infestations for at least three weeks.

Efficacy of a new spot-on formulation of selamectin plus sarolaner for cats against adult Ctenocephalides felis, flea egg production and adult flea emergence.

A new spot-on formulation of selamectin plus sarolaner was evaluated against fleas for adulticidal efficacy, and for the effect on egg production and hatching when applied to flea-infested cats. Ten male and ten female adult domestic shorthair cats were randomly assigned to one of two treatment groups based on pre-treatment flea counts. Cats received topical treatment on Day 0 in a single spot to the dorsal scapular area with either a placebo formulation or with the combination formulation at the minimal dose of 6.0mg selamectin plus 1.0mg sarolaner per kg bodyweight. On Days -1, 5, 12, 19, 26 and 33, cats were infested with approximately 100 (±5) unfed Ctenocephalides felis fleas. At 24h after treatment or 48h after subsequent flea infestation, cats were housed for a 20-h period in a cage to allow collection of flea eggs. At the end of this period, flea eggs were collected from the cages and cats were combed to remove and count live fleas. Emerged viable larvae and emerged adult fleas were counted 3days and 35days, respectively, after egg collection. The new spot-on formulation of selamectin plus sarolaner provided 100% efficacy against adult fleas up to Day 36 following a single application. Fleas on placebo-treated cats produced large numbers of eggs throughout the study, with individual counts ranging from 110 to 1256 eggs. Following treatment, four flea eggs were collected from a single selamectin/sarolaner-treated cat on Day 29, but there were no eggs collected from any other selamectin/sarolaner-treated animal during the study. No larvae or adult fleas developed from these four eggs. From the eggs collected from the placebo-treated cats, the mean percentage of live larvae and adults that emerged ranged from 67.3% to 84.2% and from 50.7% to 81.8%, respectively. A single topical treatment with a new spot-on formulation of selamectin plus sarolaner at the minimum label dose thus controlled fleas on cats and was 100% effective in preventing flea reproduction for over one month after treatment.

Efficacy of fluralaner spot-on solution against induced infestations with Rhipicephalus sanguineus on dogs.

BACKGROUND: The efficacy of fluralaner spot-on solution administered once topically against induced infestations with Rhipicephalus sanguineus was evaluated in dogs over a 12-week post-treatment period. METHODS: Six negative-controlled studies were conducted, involving a total of 112 adult dogs (57 mixed breed, 47 Beagles, eight Labradors). In each study, dogs were randomized to two groups of eight to ten dogs each. On day 0, dogs in each treated group were topically administered fluralaner spot-on solution once at a dose of 25 mg/kg body weight, while dogs in each control group were not treated. Two days before treatment, and on days 28, 56 and 84 after treatment, all dogs were infested with approximately 50 unfed, adult Rh. sanguineus ticks (sex ratio 1:1). Ticks were removed and counted on days 2, 30 (4 weeks), 58 (8 weeks), and 86 (12 weeks) after treatment to assess efficacy. RESULTS: Efficacy against ticks 2 days after treatment was 91.1 % (study 1), 98.4 % (study 2), 100 % (study 3), 97.6 % (study 4), 99.6 % (study 5), and 99.8 % (study 6). At all other assessment time points, tick efficacy was 95.4-100 %. Tick reduction in all treatment groups was significant at all assessment time points (P < 0.0001). CONCLUSIONS: A single topical administration of fluralaner spot-on solution provides a high level of therapeutic and persistent efficacy against Rh. sanguineus ticks over the subsequent 12 weeks.

Evaluation of the speed of kill of sarolaner (Simparica™) against induced infestations of three species of ticks (Amblyomma maculatum, Ixodes scapularis, Ixodes ricinus) on dogs.

The rapid speed of kill of sarolaner (Simparica™, Zoetis), a novel isoxazoline compound, was demonstrated against three tick species known to infest dogs in Europe or the United States. Efficacy was measured against an existing infestation and against subsequent weekly re-infestations for 35 days after treatment. Dogs were randomly allocated to treatment with a single oral dose of either placebo or sarolaner (2mg/kg) based on pre-treatment host-suitability tick counts. Dogs were infested with approximately 50 unfed adult Ixodes scapularis, Ixodes ricinus or Amblyomma maculatum ticks on Days-2, 7, 14, 21, 28 and 35. Tick counts were conducted at 4 (I. scapularis only), 8, 12 and 24h after treatment on Day 0 and after each subsequent re-infestation. No treatment-related adverse reactions occurred during any of these studies. Dogs in the placebo-treated groups maintained adequate tick infestations (recovery of 20-70% of applied ticks) throughout the duration of the studies. Following treatment, live tick counts were significantly reduced relative to placebo at the 8h post treatment counts indicating that sarolaner started killing existing infestations of ticks rapidly after treatment. Efficacy was 90.1% against I. ricinus, 98.8% against I. scapularis, and 99.2% against A. maculatum within 12h, and 100% efficacy was achieved at 24h after treatment against all three tick species. This speed of kill was maintained throughout the month with ≥95.7%, ≥98.7% and ≥89.6% efficacy against I. scapularis, I. ricinus, and A. maculatum, respectively, at 24h after re-infestation at least through Day 28.

Efficacy of a novel oral formulation of sarolaner (Simparica™) against five common tick species infesting dogs in the United States.

The efficacy of a single oral treatment with sarolaner (Simparica™, Zoetis), a novel isoxazoline compound, was evaluated against five tick species known to infest dogs in the United States. A total of 10 laboratory studies, two against each species, were conducted using adult purpose-bred mongrels or Beagle dogs. In each study, 16 dogs were randomly allocated to one of two treatment groups based on pre-treatment host-suitability tick counts. Dogs were infested with approximately 50 unfed adult Amblyomma americanum, Amblyomma maculatum, Dermacentor variabilis, Ixodes scapularis or Rhipicephalus sanguineus ticks on Days -2, 5, 12, 19, 26 and 33. On Day 0, dogs were treated with a placebo or a sarolaner tablet providing a minimum dose of 2 mg/kg. Tick counts were conducted 48h after treatment and after each subsequent weekly re-infestation. There were no treatment-related adverse reactions during any of the studies. Dogs in the placebo-treated group maintained tick infestations throughout the studies. Geometric mean live tick counts were significantly lower (P≤0.0001) in the sarolaner-treated group compared to the tick counts in the placebo group at all timepoints. Treatment with sarolaner resulted in ≥99.6% efficacy against existing infestations of all five tick species within 48h. The efficacy against weekly post-treatment re-infestations of all tick species was ≥96.9% for at least 35 days after treatment. Thus, a single dose of sarolaner administered orally at the minimum dosage of 2mg/kg, resulted in excellent efficacy within 48h against existing tick infestations, and against weekly re-infestations for 35 days after treatment. These studies confirmed that administration of the minimum dose of sarolaner will provide rapid treatment of existing infestations and give at least one month of control against re-infestation by the common tick species affecting dogs in the US.

Evaluation of the effectiveness of a novel oral formulation of sarolaner (Simparica™) for the treatment and control of fleas on dogs.

The efficacy of a single oral dose of a novel isoxazoline, sarolaner (Simparica™, Zoetis), for the treatment and control of flea infestations on dogs was confirmed in five laboratory studies. The studies were conducted using adult purpose-bred Beagles and/or mixed breed dogs. All animals were individually identified and housed, and were allocated randomly to treatment with either placebo or sarolaner (eight to 10 per group) based on pretreatment parasite counts. Three studies used cat flea (Ctenocephalides felis felis) strains recently isolated from the field from the US, EU, or Australia; in the fourth study a laboratory strain (KS1) with documented tolerance to a number of insecticides such as fipronil, imidacloprid, and permethrin was used. In the fifth study, dogs were infested with dog fleas, Ctenocephalides canis. Dogs were treated orally on Day 0 with a placebo or a sarolaner tablet providing a minimum dose of 2mg/kg. Dogs were infested with approximately 100 unfed, adult fleas prior to treatment and at weekly intervals post-treatment. Comb counts were conducted to determine the numbers of viable fleas at 24h after treatment and after each subsequent infestation. Efficacy against C. felis and C. canis was 99.8-100% from treatment through Day 35. In all five studies, elimination of existing infestations was achieved within 24h after dosing, with only a single live C. felis found on one dog on Day 1. Similarly, control of flea challenges was achieved within 24h after infestation throughout the 35day study periods, with only single live C. felis found on two dogs on Day 28 in one study, and on a single dog on Day 35 in another study. There were no adverse reactions to treatment with sarolaner. These studies confirmed that a single oral dose of sarolaner at 2mg/kg provided highly effective treatment of existing C. felis infestations and persistent control of C. felis on dogs for 35days after treatment. Efficacy equivalent to that seen with C. felis was confirmed against C. canis and a known insecticide-tolerant strain of C. felis.

Comparative speed of kill of sarolaner (Simparica) and spinosad plus milbemycin oxime (Trifexis) against induced infestations of Ctenocephalides felis on dogs.

BACKGROUND: Fleas are a ubiquitous ectoparasite infesting dogs and cause direct discomfort, allergic reactions and are responsible for the transmission of several pathogens. The rapid speed of kill of a parasiticide is important to alleviate the direct deleterious effects of fleas, reduce the impact of allergic responses, and break the flea life cycle. In this study, the speed of kill of a novel orally administered isoxazoline parasiticide, sarolaner (Simparica) against fleas on dogs was evaluated and compared with spinosad in combination with milbemycin oxime (Trifexis) for 5 weeks after a single oral dose. METHODS: Twenty-four dogs were randomly allocated to treatment with a single oral dose per product label of sarolaner (2 to 4 mg/kg), spinosad/milbemycin oxime (30 to 60 mg/kg / 0.2 to 0.4 mg/kg), or placebo based on pretreatment flea counts. Dogs were combed and live fleas counted at 8, 12, and 24 h after treatment and subsequent re-infestations on Days 7, 14, 21, 28, and 35. Efficacy (reduction in live flea counts) of each treatment was determined at each time point relative to counts for placebo dogs. RESULTS: There were no adverse reactions to treatment. A single oral dose of sarolaner provided ≥94.0 % efficacy (based on geometric means) within 8 h of treatment or subsequent weekly re-infestations of fleas to Day 35. By 12 h, fleas were eradicated from all dogs and they remained flea free at 24 h. Significantly greater numbers of live fleas were recovered from spinosad/milbemycin oxime-treated dogs at 8 h from Day 21 to Day 35 (P ≤ 0.0085), and at 12 and 24 h on Day 35 (P ≤ 0.0002). CONCLUSIONS: In this controlled laboratory evaluation, dogs treated with sarolaner had significantly fewer live fleas than spinosad/milbemycin oxime- treated dogs at 8 h after re-infestation from Day 21 after a single oral dose. The rapid and consistent kill of fleas after a single oral dose of sarolaner over 35 days indicates that this treatment should provide highly effective control of flea infestations, relief for dogs afflicted with flea allergy dermatitis, and also reduce the risk of transmission of flea-borne pathogens.

Comparative speed of kill of sarolaner (Simparica) and afoxolaner (NexGard) against induced infestations of Amblyomma americanum on dogs.

BACKGROUND: The lone star tick, Amblyomma americanum, infests dogs and cats in North America and is the vector of the pathogens that cause monocytic and granulocytic ehrlichiosis in dogs and humans. A parasiticide's speed of kill is important to minimize the direct and deleterious effects of tick infestation and especially to reduce the risk of transmission of tick-borne pathogens. In this study, speed of kill of a novel orally administered isoxazoline parasiticide, sarolaner (Simparica chewable tablets), against A. americanum on dogs was evaluated and compared with afoxolaner (NexGard) for 5 weeks following a single oral dose. METHODS: Based on pretreatment tick counts, 24 dogs were randomly allocated to treatment with sarolaner (2 to 4 mg/kg), afoxolaner (2.5 to 6.8 mg/kg) or a placebo. Dogs were examined and live ticks counted at 8, 12, and 24 h after treatment and subsequent re-infestations on Days 7, 14, 21, 28, and 35. Efficacy was determined at each time point relative to counts for placebo dogs. RESULTS: A single oral dose of sarolaner provided 100 % efficacy within 24 h of treatment, and consistently provided >90% efficacy against subsequent weekly re-infestations with ticks to Day 28. Significantly more live ticks were recovered from afoxolaner-treated dogs than from sarolaner-treated dogs at 24 h after infestation from Day 7 through Day 35 (P ≤ 0.0247). At 24 h, efficacy of afoxolaner declined to less than 90% from Day 14 to the end of the study. There were no adverse reactions to treatment. CONCLUSIONS: In this controlled laboratory evaluation, sarolaner had a faster speed of kill against A. americanum ticks than afoxolaner. The rapid and consistent kill of ticks by sarolaner within 24 h after a single oral dose over 28 days, suggests this treatment will provide highly effective and reliable control of ticks over the entire treatment interval, and could help reduce the risk of transmission of tick-borne pathogens by A. americanum.

Development of advantus(imidacloprid) soft chewable tablets for the treatment of Ctenocephalides felis infestations on dogs.

BACKGROUND: Studies reported here were conducted to evaluate the safety and effectiveness of advantus (imidacloprid) soft chewable tablets for the treatment of flea (Ctenocephalides felis) infestations on dogs and puppies 10 weeks of age or older and weighing 4 pounds or greater. METHODS: A pharmacokinetic study was conducted to evaluate parameters of orally administered imidacloprid. A dose confirmation study was conducted to confirm the efficacy of 0.75 mg/kg at 8, 12 or 24 hours post-treatment. A knockdown and speed of kill study was conducted to confirm the efficacy of 0.75 mg/kg dose at 0.5, 1, 4 or 24 hours post-treatment. The safety of a daily dose administered for six months at approximately 1, 3, and 5 times the maximum exposure dose of 3.75 mg/kg was evaluated in puppies. A field study was conducted to evaluate the safety and efficacy of a daily oral dose of 0.75 mg/kg for 14 days in client-owned dogs. RESULTS: The pharmacokinetic parameters of the final imidacloprid oral formulation were; Tmax 1.31 hours, Cmax 690.0 ng/mL, AUC 2615.5 h*ng/mL and half-life was 2.2 hours. The efficacy of 0.75 mg/kg BW was 98.6%, 99.9% and 100% at 8, 12 and 24 hours post-treatment, respectively. The live flea counts were significantly different (p < 0.0001) and the treatment was well tolerated. The flea counts at 1 hour post-treatment were significantly lower in the treated group and the speed of kill efficacy was 96.6% at 4 hours post-treatment in the knockdown and speed of kill study. The target animal safety study showed that the advantus soft chewable tablets administered orally to 10-week-old puppies once daily for 6 months at approximately 1, 3 and 5 times the maximum dose of 3.75 mg/kg was well tolerated and did not produce clinically relevant findings in Beagles. In the field study, efficacy of the soft chewable tablets administered daily for 14 days to flea-infested dogs was 98.2%. CONCLUSION: Imidacloprid administered orally as a soft chewable tablet for the treatment of fleas on dogs was safe and highly effective with a rapid knockdown effect and rapid elimination.

Comparative Efficacy of an Imidacloprid/Flumethrin Collar (Seresto®) and an Oral Afoxolaner Chewable (NexGard®) against Tick (Dermacentor variabilis and Amblyomma americanum) Infestations on Dogs: a Randomised Controlled Trial.

This randomised controlled laboratory study demonstrated the residual speed of efficacy of an imidacloprid/flumethrin collar (Seresto(®), Bayer) for the control of ticks (Dermacentor variabilis, Amblyomma americanum) at 6 and 12 hours postinfestation on dogs when compared to oral afoxolaner (NexGard(®), Merial). Dogs were randomised by pre-treatment tick counts: Group 1) imidacloprid 10 % (w/w) / flumethrin 4.5 % (w/w) collar, 2) afoxolaner chewable (dosage 3.1 - 6.2 mg/kg), and 3) non-treated controls. Ticks (50/species/dog) were infested on days 3, 14, 21, and 28; live (attached and non-attached) and dead attached ticks were counted 6 and 12 hours later. Efficacy against live D. variabilis at 6 hours for Group 1 was 95 - 100 % and for Group 2 was 38 - 48 %; efficacy at 12 hours for Group 1 was 97 - 100 % and for Group 2 was 27 - 59 %. Efficacy against A. americanum at 6 hours for Group 1 was 94 - 100 % and for Group 2 was < 0 - 38 %; efficacy at 12 hours for Group 1 was 98 - 100 % and for Group 2 was 1 - 40 %. Live and total (total live and dead attached) tick counts in Group 1 against both tick species were significantly lower (p ≤ 0.05) than Group 2 and 3 at all time points. The number of live or total ticks on Group 2 dogs was never significantly lower when compared to the respective number of ticks on Group 3 (controls). This study demonstrated that an imidacloprid/flumethrin collar was highly efficacious (94 - 100 %) at repelling and killing ticks on dogs at 6 and 12 hours post-infestation and was more efficacious than afoxolaner on all challenge days.

Comparative Efficacy of an Imidacloprid/Flumethrin Collar (Seresto®) and an Oral Fluralaner Chewable Tablet (Bravecto®) against Tick (Dermacentor variabilis and Amblyomma americanum) Infestations on Dogs: a Randomised Controlled Trial.

This controlled laboratory study demonstrated the residual speed of efficacy of an imidacloprid/flumethrin collar (Seresto(®), Bayer) for the control of ticks (Dermacentor variabilis, Amblyomma americanum) at 6 and 12 hours post-infestation on dogs when compared to oral fluralaner (Bravecto(®), Merck). Dogs were randomised by pre-treatment tick counts: Group 1) imidacloprid 10 % (w/w)/flumethrin 4.5 % (w/w) collar, 2) fluralaner (dosage 25.1 - 49.4 mg/kg), and 3) non-treated controls. Ticks (50/species/dog) were infested on days 3, 14, 21, 28, 42, and 56 followed by 50 D. variabilis on days 70 and 84. Live and dead attached ticks were counted 6 and 12 hours later. Efficacy against both species at 6 and 12 hours for Group 1 was 94 - 100 %. Efficacy for Group 2 against both species at 6 hours was 4 - 69 %; efficacy at 12 hours was 8 - 100 %. Live (attached and non-attached) tick counts at 6 hours in Group 1 were significantly lower (p ≤ 0.05) than counts in Group 2 and 3 on all days. At 12 hours, live counts were significantly lower (p ≤ 0.05) in Group 1 than Group 2 for D. variabilis from days 56 - 84 and for A. americanum from days 28 - 56. There were significantly fewer (p ≤ 0.05) total ticks (total live and dead attached) on dogs in Group 1 compared to Group 2 and 3 at all time points. This study demonstrated that an imidacloprid/flumethrin collar was highly efficacious (94 - 100 %) at repelling and killing ticks on dogs at 6 and 12 hours post-infestation and was more efficacious than fluralaner as early as 6 hours post-infestation on all challenge days.

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.

Efficacy of a novel topical combination of fipronil, (S)-methoprene, eprinomectin and praziquantel against adult and immature stages of the cat flea (Ctenocephalides felis) on cats.

The efficacy of a novel topical combination of fipronil 8.3% (w/v), (S)-methoprene 10% (w/v), eprinomectin 0.4% (w/v) and praziquantel 8.3% (w/v) (BROADLINE(®)) was tested against adult and immature stages of Ctenocephalides felis fleas in six studies. For that purpose, fleas from different colonies from North America, Germany and South Africa were used to induce infestations in cats under laboratory conditions. In each study, between 12 and 16 cats were allocated randomly to 2 groups. Cats in Group 1 were not treated and served as controls. Cats in Group 2 were treated once on Day 0 with BROADLINE(®) at the minimum recommended dosage of 0.12 mg/kg body weight. In 4 studies, all animals were infested experimentally with unfed C. felis (100 ± 5) on Days 2 (or 1), 7, 14, 21, 28 and 35. Live fleas were counted 24h post-treatment or infestation. In 2 additional studies, animals were infested at the same frequency with gravid C. felis fleas (100 ± 5) that were fed previously on an untreated host. Forty-eight hours post-infestation, flea eggs were collected, counted and incubated for the evaluation of the reduction of emergence of adults. The combined curative efficacy against adult fleas at 24h after treatment was 94.3% and the combined preventive efficacy values remained greater than 95.9% at 24h after 5 subsequent weekly infestations. In addition, the product reduced dramatically the emergence of new adult fleas for at least 5 weeks (>98.1% for one month and 93.2% at 5 weeks after infestation), demonstrating its efficiency in preventing environmental contamination by immature stages.

Efficacy of a novel topical combination of fipronil, (S)-methoprene, eprinomectin, and praziquantel, against the ticks, Ixodes ricinus and Ixodes scapularis, on cats.

Five controlled, blinded and randomized studies were conducted to examine the efficacy of a single topical application of a combination of fipronil, (S)-methoprene, eprinomectin, and praziquantel (BROADLINE(®), Merial) against induced infestations with Ixodes ticks on cats. Three studies investigated the efficacy against Ixodes ricinus and two against Ixodes scapularis. In each study, purpose-bred cats were assigned at random to an untreated group or to a treated group. For the studies using I. ricinus, cats were infested with 50 female ticks and a similar number of males 2 days before treatment application, and weekly afterwards on between four and six occasions. For the studies using I. scapularis, cats were infested with a total of 50 ticks (approximately 25 females and 25 males) according to the same schedule as for I. ricinus. Tick counts for the evaluation of efficacy were performed 48 h after treatment and 48 h after the subsequent weekly infestations. Weekly attachment rates to untreated cats of at least 29% for I. ricinus and at least 30% for I. scapularis demonstrated consistently that the ticks were vigorous and that the attachment rates were adequate for efficacy evaluation. In the I. ricinus studies, an efficacy of at least 93% was demonstrated for up to 37 days after the treatment. In the I. scapularis studies, the efficacy level was at least 95% 30 days after the treatment. The product was well tolerated and caused no adverse reaction.

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.

The prevention of attachment and the detachment effects of a novel combination of fipronil, amitraz and (S)-methoprene for Rhipicephalus sanguineus and Dermacentor variabilis on dogs.

A novel combination of fipronil, amitraz and (S)-methoprene (CERTIFECT™, Merial Limited, GA, USA) was evaluated for the prevention of attachment of ticks and its ability to cause detachment of ticks. For the two prevention of attachment studies, 20 purpose-bred beagles were allocated each to two equal groups based on pretreatment tick counts (treated and untreated). Each dog was exposed to 50 adult Rhipicephalus sanguineus and Dermacentor variabilis weekly starting 24h after treatment. In study 1 infestations with R. sanguineus were discontinued after Day 7 but continued to Day 28 for D. variabilis in both studies. Counts of ticks by species were made 2, 4 and 24h after exposure to ticks. Ticks not attaching to dogs were evaluated for viability. For the evaluation of detachment study, 16 purpose-bred beagles were allocated each to two equal groups based on pretreatment tick counts (treated and untreated). Each dog was infested with 50 unfed R. sanguineus and D. variabilis adults on Day -2. Ticks were thumb counted without removal on all dogs on Day -1, and at 4, 12, and 24h after treatment. Ticks were counted and removed at 48 h after treatment. Dogs treated with the novel combination had significantly (p<0.05) lower total numbers of attached R. sanguineus and D. variabilis than untreated controls at 4h through Day 7. For R. sanguineus, percent reduction of attachment at 24h after infestation through Day 29 ranged from 94.5% to 100%. For D. variabilis, the percent reduction of attachment at 24h through Day 22 was above 98.0%. These studies demonstrate that novel combination can disrupt attachment of R. sanguineus and D. variabilis for up to 28 days following treatment. Of those ticks that are exposed to the treatment, even if they do not attach to the dog and remain in the environment, greater than 90% (p<0.05) die within 24h for 2-3 weeks following treatment. Also, for those dogs infested with ticks at the time of treatment, the novel combination causes significant detachment (p<.05) starting at 12h and reaching 98.9% by 48 h after treatment. This product provides an effective means for controlling ticks infesting dogs and limiting the spread of tick transmitted diseases. Additionally, the mortality of ticks exposed to CERTIFECT will reduce infestation of the dog's environment.