afoxolaner and Flea-Infestations

One randomized, controlled clinical field study was conducted in 18 general veterinary practices throughout the USA to evaluate the safety and efficacy of a novel oral chewable combination tablet, Simparica Trio™, containing sarolaner, moxidectin and pyrantel for the treatment and prevention of fleas on dogs.. Client-owned dogs, from households of three or fewer dogs were eligible for enrollment. Four hundred and twenty-two dogs from 251 households were enrolled. Households were randomly assigned in a 2:1 ratio to treatment with either 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 afoxolaner (NexGard. Simparica Trio™ reduced geometric mean live flea counts by 99.0% by Day 30 and by 99.7% by Day 60. As a result of the rapid reduction in flea infestations, clinical signs associated with FAD substantially improved following treatment. Simparica Trio™ was well-tolerated and a diverse range of concomitant medications were administered to dogs during the course of the study. Simparica Trio™ chewable tablets were well-accepted by dogs, with the majority of flavored chewable tablets (91.9%) voluntarily consumed by free choice without, or when offered in food.. Simparica Trio™ administered orally once monthly for two consecutive treatments was safe and effective against natural flea infestations and substantially improved clinical signs associated with FAD in client-owned dogs in a field study conducted in the USA.

Topics: Acaricides; Administration, Oral; Animals; Azetidines; Dermatitis; Dog Diseases; Dogs; Drug Combinations; Female; Flea Infestations; Hospitals, Animal; Isoxazoles; Macrolides; Male; Naphthalenes; Parasite Load; Pyrantel; Siphonaptera; Spiro Compounds; Tablets; Treatment Outcome; United States

Preclinical studies have shown that the novel isoxazoline, lotilaner (Credelio™, Elanco) administered orally to dogs, produces rapid flea and tick knockdown and sustained speed of kill for at least a month post-treatment with a wide safety margin. A field study was undertaken to validate pre-clinical results.. Dogs were enrolled at 10 veterinary clinics across the United States. Qualifying households containing up to three dogs and one primary dog with at least 10 fleas were randomized 2:1 to receive lotilaner (Credelio™, Elanco) at the recommended minimum dose of 20 mg/kg, or afoxolaner (Nexgard®, Merial), administered per label, to give a minimum dose of 2.5 mg/kg. Treatments were dispensed on Days 0, 30 and 60 for administration by owners; all household dogs received the same treatment as the primary dog. Post-enrollment flea and tick counts were made on primary dogs on Days 30, 60 and 90, and all dogs were assessed for tablet palatability and safety.. For efficacy assessments, data were used from 111 lotilaner-treated dogs and 50 afoxolaner-treated dogs; for safety, 197 and 86 dogs, respectively. Percent reductions from baseline in geometric mean flea counts for the lotilaner group were 99.3, 99.9 and 100% on Days 30, 60 and 90, respectively, and for afoxolaner 98.3, 99.8 and 99.8% (P < 0.001, both groups, all days). On Day 90, 100% of lotilaner-treated dogs and 93% of afoxolaner-treated dogs were flea-free. Too few ticks were present to allow assessment. There were no differences in palatability between products (P = 0.2132), with, respectively, 94% and 96% of lotilaner and afoxolaner treatments accepted when offered by hand, in an empty food bowl or with food. Both treatments were well tolerated, alleviating clinical signs of flea allergy dermatitis (FAD) in dogs affected at enrollment.. A single owner-administered lotilaner treatment was greater than 99% effective in reducing mean flea counts within 30 days. Three consecutive monthly lotilaner treatments resulted in a 100% reduction in flea infestations, and a substantial reduction in signs of FAD. Lotilaner flavored tablets were readily accepted under field conditions. The absence of treatment-related adverse events confirms the safety of lotilaner in dogs.

Topics: Administration, Oral; Animals; Dog Diseases; Dogs; Flea Infestations; Hospitals, Animal; Insecticides; Isoxazoles; Naphthalenes; Siphonaptera; Tablets; United States

A study was designed to compare the efficacy of NexGard(®) and Bravecto™, 2 recently introduced oral ectoparasiticides containing isoxazolines, against fleas (Ctenocephalides felis) on dogs. Twenty-four healthy dogs, weighing 9.2 kg to 28.6 kg, were included in this parallel group design, randomized, and controlled efficacy study. On Day -1, the 24 dogs were allocated to 3 study groups: untreated control; Nexgard(®) treated and Bravecto™ treated. The treatments were administered on Days 0, 28 and 56 for Nexgard(®) (labelled for monthly administration), and once on Day 0 for Bravecto™ (labelled for a 12 week use). Flea infestations were performed weekly with 100 adult unfed C. felis on each dog from Days 42 to 84. Fleas were counted and re-applied at 6 and 12 h post-infestation and removed and counted 24 h post-infestation. The arithmetic mean flea count for the untreated group ranged from 62.9 to 77.6 at 24 h post-infestation, indicating vigorous flea challenges on all assessment days. Both the Nexgard(®) and Bravecto™ treated groups had statistically significantly (p<0.05) less fleas compared to the untreated group on all assessment time points and days. Significantly fewer fleas were recorded for NexGard(®) treated dogs compared to Bravecto™ treated dogs at 6 h post-infestation on Day 56, 63, 70, 77 and 84 and at 12 h post-infestation on Days 70 and 84. No statistically significant (p<0.05) differences were recorded between the treated groups at 24 h post-infestation. Efficacies recorded 6 h post-infestation for Nexgard(®) ranged from 62.8% (Day 49) to 97.3% (Day 56), and efficacies ranged from 94.1% (Day 49) to 100% (Days 42, 56, 70 and 84) at 12 h post-infestation. Efficacies recorded for Bravecto™ ranged from 45.1% (Day 84) to 97.8% (Day 42) at 6 h post-infestation, and from 64.7% (Day 84) to 100% (Days 42 and 56) at 12 h post-infestation. Efficacies observed at 24 h were 100% for both products during the study except 99.6% on Day 84 for Bravecto™.

Topics: Administration, Oral; Animals; Ctenocephalides; Dog Diseases; Dogs; Flea Infestations; Insecticides; Isoxazoles; Naphthalenes; Time Factors; Treatment Outcome

The speed of flea knockdown by different products and their duration of effectiveness are factors which affect veterinarian prescribing decisions. To further validate the month-long pulicidal effectiveness of spinosad and determine its rate of flea knockdown to that of afoxolaner, three studies were conducted in two laboratories in the United States, utilizing flea infestations from colonies which are regularly refreshed through introduction of locally caught fleas.. All study assessors were blinded, dogs were ranked by pre-study flea counts and randomized accordingly, and treatments administered on Day 0. All studies included a negative control group; two also included an afoxolaner group. In one study, flea challenges for treated and control dogs (10 per group) were completed 21 and 28 days after treatment and counts were performed 24 h later. In each of two speed-of-knockdown (SOK) studies, 36 dogs were randomized, six dogs per group, to: untreated controls; administered oral afoxolaner (2.6-6.2 mg/kg); or oral spinosad (32.1-59.2 mg/kg). In the SOK studies, live fleas from Day -1 infestations were counted after being combed off at 1 and 3 h after treatment, and after reinfestations on Day 7.. There were no treatment-related adverse events. Spinosad was 98.6% effective at 28 days post treatment. For SOK, geometric mean live flea counts for afoxolaner were not different from controls at any assessment. For spinosad, all mean counts were significantly lower than in controls (p ≤ 0.0128) except at 1 h post treatment in both studies. Spinosad was significantly more effective than afoxolaner in both studies at 3 h post treatment (p ≤ 0.0065) and post-Day 7 infestation (p ≤ 0.0054), and at 1 h post treatment (p = 0.0276) and post-Day 7 infestation in one study.. These data validate spinosad's faster onset of flea knockdown than afoxolaner against infestations present at the time of treatment, and faster residual speed of flea knockdown for at least 7 days post treatment, and confirm spinosad's extended residual speed of kill for at least 28 days post treatment.

Topics: Animals; Dog Diseases; Dogs; Drug Combinations; Drug-Related Side Effects and Adverse Reactions; Flea Infestations; Insecticides; Isoxazoles; Macrolides; Naphthalenes; Siphonaptera; Time Factors; United States

The speed of efficacy of afoxolaner (NexGard) against Ctenocephalides felis fleas was evaluated in two studies. Study A assessed the efficacy against existing fleas whereas study B assessed the efficacy against new infesting fleas. In study A, 12 dogs were allocated to the untreated group and 20 dogs to the treated group. All dogs were infested by 100 fleas each at Day -1, treated at Day 0 and flea combed at 2 h or at 6 h post treatment. In study B, 6 dogs were allocated to the untreated group and 10 to the treated group. They were infested with 100 fleas each on Days 2, 7, 14, 21 and 28. Fleas were removed and counted at 6 h post-infestation. Immediate and persistent efficacies were evaluated by counting fleas on the dogs. To evaluate induced mortality after exposure on dogs, fleas collected alive were placed in an insectarium for 24 h and assessed for viability. The immediate efficacy on dogs was significant at 6 h with 100%. The induced death of the fleas collected live from dogs 2 h after exposure was 99.7%. Concerning new infesting fleas, the observed efficacy at 6 h and the induced mortality were significantly different (p < 0.05) from the control at all time-points. At 6 h, the prophylactic efficacy was > 97% at Day 2 and Day 8 and > 90% at Day 14. The induced mortality after 6 h of exposure on dogs varied between 73.3% and 100% for the whole study.

Topics: Animals; Ctenocephalides; Dog Diseases; Dogs; Excitatory Amino Acid Antagonists; Flea Infestations; GABA Antagonists; Insect Proteins; Insecticides; Isoxazoles; Naphthalenes; Time Factors; Treatment Outcome

The sand flea Tunga penetrans is one of the agents of tungiasis, an important parasitic skin disease affecting humans and several mammalian species. Tungiasis is mainly observed in disadvantaged rural and peripheral urban communities in Latin America and sub-Saharan Africa. The dog is a major reservoir of Tunga fleas. Hematophagous adult female Tunga spp. embed and grow in their host's epidermis and cause cutaneous inflammatory disorders. NexGard Spectra. A blinded, negative-controlled field trial was conducted in a Brazilian community known to be highly endemic for tungiasis. Sixty-six dogs naturally infected with live T. penetrans were randomly allocated to a treated group (44 dogs) and an untreated control group (22 dogs). In a first phase, dogs from the treated group were treated on days 0, 30, and 60. Efficacy was evaluated on the basis of the macroscopic parasitic skin lesions (Fortaleza classification) on days 7, 14, 21, 30, 45, 60, 75, and 90. In a second phase, to evaluate natural reinfections, all dogs were treated on day 90 and evaluated every 2 weeks thereafter until at least 30% of dogs were infected with live sand fleas.. During the first phase, efficacy (reduction in live sand fleas) of 92.4% was demonstrated on day 7. From day 14 until day 90, the efficacy of NexGard Spectra. NexGard Spectra

Topics: Animals; Dog Diseases; Dogs; Female; Flea Infestations; Humans; Mammals; Tunga; Tungiasis

A veterinarian and pet owner survey (Project Jake) examined the use and safety of isoxazoline parasiticides given to dogs. Data were received during August 1-31, 2018 from a total of 2,751 survey responses. Forty-two percent (1,157) reported no flea treatment or adverse events (AE), while 58% (1594) had been treated with some parasiticide for flea control, and of those that received a parasiticide, the majority, or 83% (1,325), received an isooxazoline. When any flea treatment was given, AE were reported for 66.6% of respondents, with no apparent AE noted for 36.1%. Project Jake findings were compared to a retrospective analysis of publicly available Food and Drug Administration (FDA) and European Medicines Agency (EMA) reported AE. The number of total AE reported to FDA and EMA were comparable, although a 7 to 10 times higher occurrence of death and seizures was reported from the EMA or from outside the United States (US). Serious AE responses for death, seizures and neurological effects reported in our survey were higher than the FDA but moderately lower than the EMA reports. These sizable global data sets combined with this pre- and post-parasiticide administration survey indicated that isoxazoline neurotoxicity was not flea- and tick-specific. Post-marketing serious AE were much higher than in Investigational New Drug (IND) submissions. Although the labels have recently been updated, dogs, cats and their caregivers remain impacted by their use. These aggregate data reports support the need for continued cross-species studies and critical review of product labelling by regulatory agencies and manufacturers.

Topics: Animals; Antiparasitic Agents; Azetidines; Dog Diseases; Dogs; Flea Infestations; Isoxazoles; Naphthalenes; Spiro Compounds; Tick Infestations

Veterinary clinic transaction records from the USA were examined to determine dog owner purchase patterns for three prescription ectoparasiticides. In-clinic purchases of formulations of fluralaner (with 12-week duration per dose) were compared with dog owner purchases of afoxolaner and spinosad (both with 4 week duration per dose) in a population of 231,565 dogs over a 12 month period. Prior studies in human and animal medicine have suggested that patients more closely adhere to prescriber dosing recommendations when they receive a longer-duration medication.. Veterinary clinic transaction records were examined for the period June 2014 through March 2017 using records from approximately 650 veterinary clinics. Ectoparasiticide purchase patterns were compared for two products (afoxalaner and spinosad) with monthly dosing and one product (fluralaner) with an extended (12 week) dosing interval. The average dog owner who obtained fluralaner purchased significantly more months of flea/tick protection (5.7 months) over the 12-month study period than the average dog owner that selected either afoxolaner (4.6 months) or spinosad (3.3 months). The proportion of dog owners who obtained only one dose of ectoparasiticide per 12-month period was 42% for fluralaner, 30% for afoxolaner and 37% for spinosad. The proportion of dog owners who obtained 2 doses or less per 12-month period was 67% for fluralaner, 52% for afoxoalaner and 67% for spinosad. Owners that obtained fluralaner were significantly more likely to obtain 7.0-12.0 months of flea and tick protection and significantly less likely to purchase 1.0-6.9 months compared with dog owners who purchased afoxolaner or spinosad.. Dog owners who obtained a flea and tick medication with a longer duration of action acquired significantly more months of protection in a year than dog owners who obtained shorter duration (1 month) products. Dog owners were better able to adhere to veterinary recommendations on ectoparasites control with a longer-acting flea/tick medication.

Topics: Animals; Dog Diseases; Dogs; Drug Combinations; Flea Infestations; Hospitals, Animal; Humans; Insecticides; Isoxazoles; Macrolides; Medication Adherence; Naphthalenes; Ownership; Prescription Drugs; Records; Siphonaptera; Ticks; United States; Veterinary Drugs; Veterinary Medicine

A study was conducted to evaluate and compare the effectiveness of two different oral flea and tick products to control flea infestations, reduce pruritus and minimize dermatologic lesions over a 12 week period on naturally infested dogs in west central FL USA.. Thirty-four dogs with natural flea infestations living in 17 homes were treated once with a fluralaner chew on study day 0. Another 27 dogs living in 17 different homes were treated orally with an afoxolaner chewable on day 0, once between days 28-30 and once again between days 54-60. All products were administered according to label directions by study investigators. Flea populations on pets were assessed using visual area counts and premise flea infestations were assessed using intermittent-light flea traps on days 0, 7, 14, 21, and once between days 28-30, 40-45, 54-60 and 82-86. Dermatologic assessments were conducted on day 0 and once monthly. Pruritus assessments were conducted by owners throughout the study. No concurrent treatments for existing skin disease (antibiotics, anti-inflammatories, anti-fungals) were allowed.. Following the first administration of fluralaner or afoxolaner, flea populations on pets were reduced by 99.0 % and 99.3 %, respectively within 7 days. Flea populations on the fluralaner treated dogs were 0 (100 % efficacy) on days 54-60 and 82-86 after the administration of a single dose on day 0. Administration of 3 monthly doses of afoxolaner reduced flea populations by 100 % on days 82-86. Flea numbers in indoor-premises were markedly reduced in both treatment groups by days 82-86, with 100 % and 98.9 % reductions in flea trap counts in the fluralaner and afoxolaner treatment groups, respectively. Marked improvement was observed in FAD lesion scoring, Atopic Dermatitis lesions scoring (CADESI-4) and pruritus scores with both formulations.. In a clinical field investigation conducted during the summer of 2015 in subtropical Florida, a single administration of an oral fluralaner chew completely eliminated dog and premises flea infestations and markedly reduced dermatology lesions and pruritus. Three monthly doses of the afoxolaner chewable also eliminated flea infestations in dogs, markedly reduced premises' flea populations and similarly improved dermatology lesions and pruritus.

Topics: Animals; Dog Diseases; Dogs; Flea Infestations; Florida; Insecticides; Isoxazoles; Naphthalenes; Pruritus; Siphonaptera

A study was conducted to evaluate the effectiveness of afoxolaner chewables to control flea populations in naturally infested dogs in private residences in Tampa FL, USA. Evaluations of on-animal and premises flea burdens, flea sex structure and fed-unfed premises flea populations were conducted to more accurately assess flea population dynamics in households.. Thirty seven naturally flea infested dogs in 23 homes in Tampa, FL were enrolled in the study and treated with afoxolaner chewables. Chewables (NexGard® Chewables; Merial) were administered according to label directions by study investigators on study day 0 and once again between study days 28 and 30. Flea infestations on pets were assessed using visual area thumb counts and premises flea infestations were assessed using intermittent-light flea traps on days 0, 7, 14, 21, and once between study days 28-30, 40-45, and 54-60.. Within 7 days of administration of afoxolaner chewable tablets, flea counts on dogs were reduced by 99.3%. By one month post-treatment, total flea counts on dogs were reduced by 99.9%, with 97.3% (36/37) of the dogs being flea free. Following the second dosing on study day 28-30, total on-dog flea burden was reduced by 100% on days 40-45 and 54-60. On day 0, the traps collected a geometric mean of 18.2 fleas. Subsequent reductions in emerging flea populations were 97.7 and 100% by days 28-30 and 54-60, respectively. There were 515 total fleas (Ctenocephalides felis felis) collected in the intermittent light flea traps on day 0, and 40.4% of those fleas displayed visual evidence of having fed. Seven days after initial treatment, only 13.1% of the fleas contained blood and by day 14 only 4.9% of the fleas collected in traps displayed evidence of having fed. On day 0, prior to treatment, 60% of the unfed fleas collected in intermittent-light flea traps were females, but by days 28-30, unfed males accounted for 78% of the population.. This in-home investigation conducted during the summer of 2014 in subtropical Tampa, FL demonstrated that afoxolaner chewables rapidly and effectively eliminated flea populations in infested dogs and homes.

Topics: Administration, Oral; Animals; Animals, Domestic; Dog Diseases; Dogs; Drug Evaluation; Female; Flea Infestations; Insecticides; Isoxazoles; Male; Naphthalenes; Pest Control; Pets; Siphonaptera

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.

Topics: Administration, Oral; Animals; Antiparasitic Agents; Ctenocephalides; Dog Diseases; Dogs; Female; Flea Infestations; Isoxazoles; Male; Naphthalenes; Parasite Egg Count; Random Allocation; Treatment Outcome

Topics: Acaricides; Animals; Dogs; Flea Infestations; Insecticides; Isoxazoles; Naphthalenes; Siphonaptera; Tick Infestations; Ticks

Afoxolaner is an isoxazoline compound characterized by a good safety profile and extended effectiveness against fleas and ticks on dogs following a single oral administration. In vitro membrane feeding assay data and in vivo pharmacokinetic studies in dogs established an afoxolaner blood concentration of 0.1-0.2 μg/ml to be effective against both fleas (Ctenocephalides felis) and ticks (Dermacentor variabilis). Pharmacokinetic profiles in dogs following a 2.5mg/kg oral dosage demonstrated uniform and predictable afoxolaner plasma concentrations above threshold levels required for efficacy for more than one month. Dose ranging and a 5-month multi-dose experimental study in dogs, established that the 2.5mg/kg oral dosage was highly effective against fleas and ticks, and produced predictable and reproducible pharmacokinetics following repeated dosing. Mode of action studies showed that afoxolaner blocked native and expressed insect GABA-gated chloride channels with nanomolar potency. Afoxolaner has comparable potency between wild type channels and channels possessing the A302S (resistance-to-dieldrin) mutation. Lack of cyclodiene cross-resistance for afoxolaner was confirmed in comparative Drosophila toxicity studies, and it is concluded that afoxolaner blocked GABA-gated chloride channels via a site distinct from the cyclodienes.

Topics: Animals; Antiparasitic Agents; Chloride Channels; Cockroaches; Dog Diseases; Dogs; Drosophila melanogaster; Electrophysiological Phenomena; Female; Flea Infestations; Isoxazoles; Male; Naphthalenes; Oocytes; Protein Binding; Random Allocation; Siphonaptera; Tick Infestations; Ticks; Xenopus laevis

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.

Topics: Administration, Oral; Animals; Ctenocephalides; Dog Diseases; Dogs; Female; Flea Infestations; Isoxazoles; Male; Naphthalenes; Parasite Egg Count; Parasite Load; Treatment Outcome

The pharmacokinetics of afoxolaner in dogs was evaluated following either intravenous or after oral administration of NEXGARD(®), a soft chewable formulation. Afoxolaner is a member of one of the newest classes of antiparasitic agents, known as antiparasitic isoxazolines. The soft chewable formulation underwent rapid dissolution, and afoxolaner was absorbed quickly following oral administration of the minimum effective dose of 2.5mg/kg, with maximum plasma concentrations (Cmax) of 1,655 ± 332 ng/mL observed 2-6h (Tmax) after treatment. The terminal plasma half-life was 15.5 ± 7.8 days, and oral bioavailability was 73.9%. Plasma concentration-versus-time curves fit a 2-compartment model and increased proportionally with dose over the oral dose range of 1.0-4.0mg/kg, and over the oral dose range from 1.0 to 40 mg/kg. Following an intravenous dose of 1mg/kg, the volume of distribution (Vd) was 2.68 ± 0.55 L/kg, and the systemic clearance was 4.95 ± 1.20 mL/h/kg. Afoxolaner plasma protein binding was >99.9% in dogs. One major metabolite, formed following hydroxylation of afoxolaner, was identified in dog plasma, urine and bile. When afoxolaner is administered orally, there is a strong correlation between afoxolaner plasma concentration and efficacy with EC90 values of 23 ng/mL for Ctenocephalides felis and ≥ 100 ng/mL for Rhipicephalus sanguineus sensu lato and Dermacentor variabilis. The pharmacokinetic properties of afoxolaner are suited for a monthly administration product because the fast absorption and long terminal half-life support a rapid onset of action while ensuring month-long efficacy.

Topics: Administration, Intravenous; Administration, Oral; Animals; Antiparasitic Agents; Area Under Curve; Dog Diseases; Dogs; Female; Flea Infestations; Isoxazoles; Male; Naphthalenes; Protein Binding; Tick Infestations

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.

Topics: Administration, Oral; Animals; Antiparasitic Agents; Ctenocephalides; Dog Diseases; Dogs; Female; Flea Infestations; Isoxazoles; Male; Naphthalenes; Random Allocation; Time