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Background: Erythemato‐ceruminous otitis externa (ECOE) is frequently seen in dogs affected with an allergic skin disease, with recurrent secondary bacteria and yeast overgrowths (detected on cytological examination). Objectives: The objective of the study was to compare the efficacy and safety of an ear spray containing only hydrocortisone aceponate glucocorticoid diester (HCA) to a control product (CTRL), an approved otic formulation containing prednisolone‐miconazole‐polymyxin combination, in dogs with ECOE. Animals: In total, 97 and 104 dogs with ECOE were respectively randomly assigned to the tested ear treatment product group (HCA) or the commercially available ear treatment control product group (CTRL). Materials and Methods: Dogs were treated for 7–14 days, as needed. At Day (D)0, D7, D14, D28 and D42, Otitis Index Score‐3, hearing test, pruritus and pain visual analogue scales, and cytological scores were graded. The overall response to treatment also was assessed. Results: All clinical parameters decreased rapidly and in a similar way without any significant difference at any time between treatment groups. A good‐to‐excellent response to treatment was seen in >90% of dogs of both groups as early as D14. The treatment was considered safe in all dogs. Conclusions and Clinical Relevance: A 7‐ to 14‐day ear topical application of HCA alone to dogs with ECOE accompanied with bacterial and/or fungal (yeast) overgrowth was safe and led to no statistical difference in improvement of clinical scores relative to the CTRL combination. Based on these results, it may be necessary to reconsider the routine use of antimicrobial drugs such as antibiotics and antifungals as a first‐line treatment for ECOE that is likely to have been caused by an allergic reaction. [ABSTRACT FROM AUTHOR]

Background: 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® is an orally administered endectocide for dogs, a co-formulation of the isoxazoline afoxolaner and the macrocyclic lactone milbemycin oxime. The objective of this study was to assess the efficacy of this product against canine tungiasis. Methods: 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. Results: 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® was 100%. In the second phase, all dogs were free of live T. penetrans from 15 until 45 days after the day 90 treatment; 60 days post-treatment, 11% of dogs were reinfected, and 75 days post-treatment, 40% of dogs were reinfected. Conclusions: NexGard Spectra® was demonstrated to be highly effective against canine tungiasis. In addition to an obvious beneficial effect on the health and welfare of the treated dog, the use of this product may have a one-health benefit on human cases by controlling the main reservoir of sand fleas. [ABSTRACT FROM AUTHOR]

Introduction: This study aimed to determine the incidence of canine and feline tick paralysis cases presenting to two veterinary emergency hospitals before and after the introduction of new generation prophylactic acaricides. Methods: This was a retrospective study, investigating the number of tick paralysis cases presenting to two emergency and critical care veterinary hospitals in South‐East Queensland, from 2008 to 2021. A total of 10,914 dogs and 3696 cats were included over the course of the study. To assess if the introduction of new generation prophylactics in 2015 has coincided with any variation in case numbers, data for each species were analysed graphically and numerically in the first instance, then interrupted time series analyses were performed for the dog and cat data independently. Results: Accounting for seasonal and climatic variation, we estimated a 54.8% reduction in dog (95% CI 45.3%–62.7%) and 44% reduction in cat (95% CI 19.5%–46%) tick paralysis cases presenting to these two clinics. This reduction corresponded with the timing of new generation prophylactic agents being introduced, including isoxazolines and imidacloprid/flumethrin impregnated collars. Conclusion: In the population studied, a significant reduction in the incidence of tick paralysis cases treated by veterinarians has occurred from 2015 onwards and was found to be associated with the timing of the release of new generation acaricidal products. [ABSTRACT FROM AUTHOR]

Background: This study evaluated the timing of dog owner ectoparasiticide purchases to estimate administration compliance and assess the consequent impact of dose purchase gaps on the proportion of time that dogs were protected over a 12-month period. Methods: Ectoparasiticide purchase transactions over a 12-month period were evaluated for 626 US veterinary hospitals to determine dose purchase timing and identify consequent gaps between dose administration in dogs. Orally administered prescription ectoparasitic medications with active ingredients from the isoxazoline family (afoxolaner, fluralaner, lotilaner, or sarolaner) were included in the analysis. A period was calculated for each of the four isoxazoline-containing medications that represented the duration of protection provided by two doses of ectoparasiticide plus the average gap between these two doses. The maximum percentage of time possible for ectoparasiticide protection for this aggregate period was then calculated for each active ingredient. Results: Ectoparasiticide transaction records of owners were analyzed for 506,637 dogs. These showed that 43% of dog owners purchased just one dose over the 12-month period considered. If a dog owner purchased more than one dose, then the timing of their transactions could create a time gap between the completion of ectoparasite protection from the first dose and onset of protection from the subsequent purchase and administration of the second dose. Such gaps were observed in purchases made by 31–65% of dog owners, depending on the selected active ingredient and number of doses. The average gap duration between dose purchases was calculated for all possible dose combinations over 12 months of ectoparasite protection. Time gaps between the first and second doses are as follows: for sarolaner, 20.3 weeks; for afoxolaner, 12.9 weeks; for fluralaner ,12.8 weeks; and for lotilaner, 8.9 weeks. The proportion of time when protection was provided during the aggregate period between administration of the first and second doses was as follows: for fluralaner, 65%; for lotilaner, 49%; for afoxolaner, 40%; and for sarolaner, 30%. Conclusions: Dog owner ectoparasiticide purchase transactions showed that there were time gaps between doses leading to reduced ectoparasite protection. The longer re-administration interval for fluralaner, a consequence of its extended duration of activity, resulted in dog owners gaining the greatest proportion of ectoparasite protection time with this medication compared with shorter-acting monthly re-treatment medications. [ABSTRACT FROM AUTHOR]

Abstract 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.

Abstract Background The black-legged (or deer) tick, Ixodes scapularis, commonly infests dogs in the USA and is the vector of important zoonotic pathogens, including Borrelia burgdorferi, the causative agent of Lyme disease. Rapid onset of activity is important in reducing the feeding activity of ticks, thereby reducing the possibility of transmission of infections. The speed of kill of a novel oral combination product, Simparica Trio™ containing sarolaner, moxidectin and pyrantel was evaluated in a well-controlled laboratory study against an existing infestation and subsequent weekly induced infestations of I. scapularis ticks on dogs. Methods Dogs were allocated randomly based on host suitability tick counts to treatment with a single 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). All dogs were infested with approximately 50 unfed adult I. scapularis ticks at a 1:1 sex ratio on Days −2, 7, 14, 21, 28 and 35. Tick counts were conducted at 8, 12 and 24 h after treatment on Day 0 and after each subsequent infestation. Results No treatment-related adverse events occurred during the study. Dogs in the placebo-treated group maintained adequate tick infestations for the duration of the study. Day 0 tick counts at 8 h after treatment with Simparica Trio™ were reduced relative to placebo against an existing infestation with efficacy of 67.5%, demonstrating that Simparica Trio™ started killing ticks soon after treatment. Efficacy was 98.4 % at 12 h and 99.4% at 24 h. Rapid speed of kill was maintained throughout the month, with efficacy of ≥ 94.2% at 24 h after re-infestation through Day 28. Conclusions A single dose of Simparica Trio™ administered orally to dogs at the minimum label dose of 1.2 mg/kg sarolaner, 24 µg/kg moxidectin and 5 mg/kg pyrantel (as pamoate salt) was safe and began to kill existing I. scapularis ticks within 8 h after treatment and resulted in ≥ 94.2% efficacy within 24 h against re-infestations for a month.

Background: Leishmania infantum is the etiological agent of visceral leishmaniasis (VL) in the New World, where the sand fly Lutzomyia longipalpis and domestic dogs are considered the main vector and host reservoirs, respectively. Systemic insecticides have been studied as an alternative to control vector-borne diseases, including VL. Fluralaner, an isoxazoline class compound, is a systemic insecticide used in dogs, with proven efficiency against different species of phlebotomine sand flies. However, to date no studies have demonstrated the efficacy of fluralaner on Lu. longipalpis. The aim of this study was to evaluate the insecticidal effect of fluralaner (Bravecto®) on the sand fly Lu. longipalpis after blood meal in treated dogs. Methods: Healthy mongrel dogs (n = 8) were recruited from the Zoonoses Control Center in the city of Natal, Rio Grande do Norte, Brazil, and randomized into two groups: fluralaner treated (n = 4) and non-treated control (n = 4). Colony-reared female specimens of Lu. longipalpis (n = 20) were allowed to feed on all dogs for 40 min before treatment (for fluralaner-treated dogs), at day 1 after treatment and then monthly until 1 year post-treatment. Results: In the treatment group, there was 100% mortality of Lu. longipalpis for up to 5 months after treatment initiation, decreasing to 72.5% at 6 months post-treatment initiation. The efficacy of fluralaner ranged from 100% at day 1 (P = 0.0002) to 68% (P = 0.0015) at 6 months, decreasing to 1.4% at 1 year post-treatment. Sand fly mortality carried out blood meal in non-treated control dogs remained constant at ≤ 15%. Conclusions: Taken together, our results suggest that fluralaner may be used as a control strategy for VL in dogs in VL endemic areas. [ABSTRACT FROM AUTHOR]

Background: Recent reports indicate that the isoxazoline compounds have the potential to provide safe and effective treatment of canine generalized demodicosis, a condition that has been traditionally difficult to cure. Controlled field studies are needed to confirm this potential. A study was therefore initiated to investigate the efficacy of a single oral or spot-on treatment with fluralaner, an isoxazoline, compared with multiple topical treatments with imidacloprid-moxidectin, in dogs naturally affected by generalized demodicosis. Methods: Veterinary clinics in 5 European countries enrolled 134 dogs diagnosed with generalized demodicosis. Dogs were randomized to treatment with either fluralaner chewables, fluralaner spot-on, or topical imidacloprid-moxidectin in a 2:2:1 ratio. Both fluralaner formulations were administered once, at the approved dose rate, on Day 0. Imidacloprid-moxidectin was administered per label on Day 0, and every 4 weeks, more frequently if necessary. At each visit (Days 0, 28, 56, 84), dogs were monitored for demodectic mites using deep skin scrapings and observed for health and for severity of skin lesions. Treatment was considered efficacious if more than 90% of the dogs were free of live mites at both Days 56 and 84. Results: Of 124 dogs completing the study, 57 were diagnosed with juvenile-onset demodicosis and 67 with the adult-onset form. A single treatment with oral or spot-on fluralaner was efficacious, each eliminating mites from at least 98.0% of treated dogs on Days 56 and 84. Against juvenile-onset demodicosis, efficacy of the oral and spot-on formulations was 96.0% and 100%, respectively, and against adult-onset demodicosis 100% and 96.7%. Multiple administrations of imidacloprid-moxidectin were not efficacious, eliminating mites from 87.5% of dogs (92.0% with juvenile-onset demodicosis cured; 81.8% with adult-onset demodicosis). All groups showed a marked reduction in skin lesions by Day 28, with continuing clinical improvement at each subsequent visit through Day 84. There were no treatment-related adverse events. Conclusions: A single administration of fluralaner chewables or fluralaner spot-on is highly effective against with juvenile-onset and adult-onset forms of generalized canine demodicosis. Topically applied imidacloprid-moxidectin at weekly to monthly intervals over the 84-day study did not achieve the proportion of mite-free dogs required to demonstrate efficacy. [ABSTRACT FROM AUTHOR]

Background: Rabacfosadine (RAB), a novel antineoplastic agent conditionally licensed for the treatment of lymphoma in dogs, is efficacious in both naïve and previously treated dogs. Its use in combination with L‐asparaginase (L‐ASP) has not been studied. Hypothesis/Objectives: To evaluate the safety and efficacy of L‐ASP given concurrently with RAB in dogs with relapsed multicentric lymphoma. Animals Fifty‐two dogs with relapse of lymphoma after treatment with at least 1 doxorubicin‐based chemotherapy protocol. Methods: Open‐label, multicenter, prospective single‐arm clinical trial. Dogs were treated with RAB at 1.0 mg/kg IV every 21 days for up to a total of 5 doses. L‐asparaginase was administered at 400 IU/kg SQ concurrently with the first 2 treatments of RAB. Results: The overall response rate (ORR) for all dogs was 67%, with 19 dogs (41%) achieving a complete response (CR). The median progression‐free survival time (MPFS) was 63 days (range 5‐428 days). Dogs experiencing a CR as their best response had an MPFS of 144 days (range 44‐428 days). Adverse events were similar to previous studies evaluating single agent RAB. Failure to achieve a CR and having previously received L‐ASP were negative prognostic factors on multivariate analysis. Conclusions and Clinical Importance: Concurrent RAB/L‐ASP appears to be both efficacious and safe for treating relapsed multicentric lymphoma in dogs. Adverse events were most often mild and no unexpected toxicoses were observed. [ABSTRACT FROM AUTHOR]

Background: The black-legged (or deer) tick, Ixodes scapularis, commonly infests dogs in the USA and is the vector of important zoonotic pathogens, including Borrelia burgdorferi, the causative agent of Lyme disease. Rapid onset of activity is important in reducing the feeding activity of ticks, thereby reducing the possibility of transmission of infections. The speed of kill of a novel oral combination product, Simparica Trio™ containing sarolaner, moxidectin and pyrantel was evaluated in a well-controlled laboratory study against an existing infestation and subsequent weekly induced infestations of I. scapularis ticks on dogs. Methods: Dogs were allocated randomly based on host suitability tick counts to treatment with a single 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). All dogs were infested with approximately 50 unfed adult I. scapularis ticks at a 1:1 sex ratio on Days −2, 7, 14, 21, 28 and 35. Tick counts were conducted at 8, 12 and 24 h after treatment on Day 0 and after each subsequent infestation. Results: No treatment-related adverse events occurred during the study. Dogs in the placebo-treated group maintained adequate tick infestations for the duration of the study. Day 0 tick counts at 8 h after treatment with Simparica Trio™ were reduced relative to placebo against an existing infestation with efficacy of 67.5%, demonstrating that Simparica Trio™ started killing ticks soon after treatment. Efficacy was 98.4 % at 12 h and 99.4% at 24 h. Rapid speed of kill was maintained throughout the month, with efficacy of ≥ 94.2% at 24 h after re-infestation through Day 28. Conclusions: A single dose of Simparica Trio™ administered orally to dogs at the minimum label dose of 1.2 mg/kg sarolaner, 24 µg/kg moxidectin and 5 mg/kg pyrantel (as pamoate salt) was safe and began to kill existing I. scapularis ticks within 8 h after treatment and resulted in ≥ 94.2% efficacy within 24 h against re-infestations for a month. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Otodectes cynotis , commonly known as "the ear mite," is a highly contagious ectoparasite and a significant cause of otitis externa in canines. The objective of the current study was to determine the efficacy of the isoxazoline afoxolaner (Nexgard®), and the combination of afoxolaner with milbemycin oxime (Nexgard Spectra®), in dogs naturally infested with O. cynotis. In total, 32 infested client-owned dogs from two different sites in Greece were included. The animals were randomly divided into four equal groups based on their infestation score. Group 1 served as the negative control, group 2 received one oral administration of Nexgard (Day 0), group 3 received two monthly oral administrations of Nexgard (Days 0, 30), and group 4 received two monthly oral administrations of Nexgard Spectra (Days 0, 30), according to label instructions. Otoscopic examinations for mites and observations on debris/cerumen in the ears were carried out on Days 0, 15, 30, and 45. A quantitative assessment of ear mites by ear duct flushing and live mite counts was performed on Day 45. The results demonstrated that a single oral dose of afoxolaner and two monthly doses of afoxolaner or afoxolaner with milbemycin oxime resulted in a 99.9% reduction in live mite counts compared to the untreated control group by Day 45. Additionally, treated dogs showed improved clinical symptoms, such as ear cerumen/debris decrease, while untreated dogs experienced worsening symptoms over the study duration. No adverse events were reported. Overall, these results support the use of afoxolaner-based products to treat O. cynotis infestation in dogs. • Afoxolaner and afoxolaner with milbemycin reduce Otodectes cynotis mites in dogs by 99.9%. • Treatments with afoxolaner reduce ear cerumen and debris in naturally infested dogs. • Both treatments are safe, well-tolerated by the dogs and with no adverse events. [ABSTRACT FROM AUTHOR]

Abstract Background Lotilaner is a new oral ectoparasiticide from the isoxazoline class developed for the treatment of flea and tick infestations in dogs. It is formulated as pure S-enantiomer in flavoured chewable tablets (Credelio™). The pharmacokinetics of lotilaner were thoroughly determined after intravenous and oral administration and under different feeding regimens in dogs. Methods Twenty-six adult beagle dogs were enrolled in a pharmacokinetic study evaluating either intravenous or oral administration of lotilaner. Following the oral administration of 20 mg/kg, under fed or fasted conditions, or intravenous administration of 3 mg/kg, blood samples were collected up to 35 days after treatment. The effects of timing of offering food and the amount of food consumed prior or after dosing on bioavailability were assessed in a separate study in 25 adult dogs. Lotilaner blood concentrations were measured using a validated liquid chromatography/tandem mass spectrometry (LC-MS/MS) method. Pharmacokinetic parameters were calculated by non-compartmental analysis. In addition, in vivo enantiomer stability was evaluated in an analytical study. Results Following oral administration in fed animals, lotilaner was readily absorbed and peak blood concentrations reached within 2 hours. The terminal half-life was 30.7 days. Food enhanced the absorption, providing an oral bioavailability above 80% and reduced the inter-individual variability. Moreover, the time of feeding with respect to dosing (fed 30 min prior, fed at dosing or fed 30 min post-dosing) or the reduction of the food ration to one-third of the normal daily ration did not impact bioavailability. Following intravenous administration, lotilaner had a low clearance of 0.18 l/kg/day, large volumes of distribution Vz and Vss of 6.35 and 6.45 l/kg, respectively and a terminal half-life of 24.6 days. In addition, there was no in vivo racemization of lotilaner. Conclusions The pharmacokinetic properties of lotilaner administered orally as a flavoured chewable tablet (Credelio™) were studied in detail. With a Tmax of 2 h and a terminal half-life of 30.7 days under fed conditions, lotilaner provides a rapid onset of flea and tick killing activity with consistent and sustained efficacy for at least 1 month.

Abstract Background Amblyomma cajennense is the main vector of Rickettsia rickettsii which causes Brazilian spotted fever. This adult tick preferably infests horses and capybaras, but has low host specificity during its immature stages, thus posing a threat to humans and dogs. In this study, the efficacy of sarolaner (Simparic™/Simparica®, Zoetis) when administered once orally to dogs at 2 mg/kg was evaluated against induced infestations of A. cajennense nymphs for up to 35 days after treatment. Methods Based on pretreatment tick counts, 20 dogs were randomly allocated to treatment with sarolaner (Simparic™) dosed at 2 mg/kg of body weight or a placebo on Day 0 of the study. Artificial infestations were performed using laboratory raised A. cajennense nymphs on study days -2, 5, 12, 19, 26 and 33. Efficacy was determined at 48 h post-treatment or post-infestation at each time point relative to the counts for dogs that received placebo. Results There were no adverse reactions to treatment. A single dose of sarolaner (Simparic™) provided 100% efficacy on study days 2, 7 and 14; and ≥ 99.6% on days 21, 28 and 35. Geometric mean live tick counts for sarolaner were significantly lower than those for placebo on all days (P

Background: This study aimed to evaluate the safety and efficacy of reduced-dosage ketoprofen with or without tramadol in dogs. Five healthy dogs receiving standard-dosage ketoprofen (2 mg/kg SC, then 1 mg/kg PO daily) comprised Group A. Twenty dogs with osteoarthritis were randomized to receive reduced-dosage ketoprofen (0.5 mg/kg SC once; 0.25 mg/kg PO daily) alone (Group B) or in combination with tramadol (5 mg/kg/day PO) (Group C). Treatments were administered for 28 days. Platelet aggregation time (PAT), gastrointestinal (GI) endoscopy and glomerular filtration rate (GFR) were performed up to 60 days after treatment initiation. Pain was scored using a validated clinical metrology instrument up to D120. Data were analyzed with general linear mixed model for repeated measures (α = 0.05). Results: PAT was not different between groups but was increased with time for all groups. GI lesion scores were higher in Group A than Groups B and C (day 28; P = 0.005) and were increased with time for Group A (P = 0.005). GFR was lower in Group A than Groups B and C (day 28; P < 0.01) and were decreased with time for group A (P < 0.001). Standard-dosage ketoprofen administration resulted in clinically relevant adverse effects. Pain score decreased in both treated groups (B and C) from D0 to D28. Need of rescue analgesia from D29 to D120 was higher in Group B than in Group C (P = 0.039). Conclusions: The long-term safety profile of reduced-dosage ketoprofen is similar whether the drug is administered alone or in combination with tramadol to dogs with osteoarthritis. Analgesic efficacy of the combination looks attractive. [ABSTRACT FROM AUTHOR]

Background: Lotilaner is a new oral ectoparasiticide from the isoxazoline class developed for the treatment of flea and tick infestations in dogs. It is formulated as pure S-enantiomer in flavoured chewable tablets (Credelio™). The pharmacokinetics of lotilaner were thoroughly determined after intravenous and oral administration and under different feeding regimens in dogs. Methods: Twenty-six adult beagle dogs were enrolled in a pharmacokinetic study evaluating either intravenous or oral administration of lotilaner. Following the oral administration of 20 mg/kg, under fed or fasted conditions, or intravenous administration of 3 mg/kg, blood samples were collected up to 35 days after treatment. The effects of timing of offering food and the amount of food consumed prior or after dosing on bioavailability were assessed in a separate study in 25 adult dogs. Lotilaner blood concentrations were measured using a validated liquid chromatography/tandem mass spectrometry (LC-MS/MS) method. Pharmacokinetic parameters were calculated by non-compartmental analysis. In addition, in vivo enantiomer stability was evaluated in an analytical study. Results: Following oral administration in fed animals, lotilaner was readily absorbed and peak blood concentrations reached within 2 hours. The terminal half-life was 30.7 days. Food enhanced the absorption, providing an oral bioavailability above 80% and reduced the inter-individual variability. Moreover, the time of feeding with respect to dosing (fed 30 min prior, fed at dosing or fed 30 min post-dosing) or the reduction of the food ration to one-third of the normal daily ration did not impact bioavailability. Following intravenous administration, lotilaner had a low clearance of 0.18 l/kg/day, large volumes of distribution Vz and Vss of 6.35 and 6.45 l/kg, respectively and a terminal half-life of 24.6 days. In addition, there was no in vivo racemization of lotilaner. Conclusions: The pharmacokinetic properties of lotilaner administered orally as a flavoured chewable tablet (Credelio™) were studied in detail. With a Tmax of 2 h and a terminal half-life of 30.7 days under fed conditions, lotilaner provides a rapid onset of flea and tick killing activity with consistent and sustained efficacy for at least 1 month. [ABSTRACT FROM AUTHOR]

Background: Lotilaner (Credelio™) is the newest member of the novel isoxazoline chemical class to be developed to treat canine ectoparasitism. Administered orally, lotilaner is rapidly absorbed with peak blood levels occurring within 2 h post-treatment. A study was undertaken to determine the earliest onset of lotilaner's efficacy against existing flea infestations. Methods: From 72 Beagles, 64 qualifying dogs were ranked in descending order of flea counts from a Day -8 infestation and placed into eight blocks. Within blocks, eight dogs were randomly allocated among eight groups: Groups 1 to 4 were treated orally with lotilaner, at as close as possible to the minimum dose rate of 20 mg/kg within 30 (± 5) minutes after feeding; Groups 5 to 8 were untreated controls. All dogs were infested with 100 ± 5 fleas on Day -2, and whole-body flea counts were completed at 30 min and one, two and 8 h after treatment. Efficacy calculations were based on arithmetic and geometric means if an adequate infestation (at least six of eight untreated dogs with a flea retention of ≥ 50%) was demonstrated in the equivalent control group. Results: Adequate infestations were established in all control groups. At 30 min and 1 h post-treatment, relative to the matching untreated control group, there were no significant reductions in mean flea counts in lotilaner-treated dogs, although moribund fleas were evident at 1 h post-treatment. At 2 h after treatment, compared with the equivalent control group, the geometric mean flea count reduction in the lotilaner group was 64.0% (t(7) = 2.86, P = 0.0242). At 8 h after treatment, lotilaner efficacy was 99.6%. There were no treatment-related adverse events. Conclusion: This study demonstrates that lotilaner flavored chewable tablets are well tolerated and begin to kill fleas within 2 h of treatment, achieving 99.6% efficacy within 8 h. Lotilaner can therefore be used to quickly alleviate the flea irritation that arises from existing infestations. [ABSTRACT FROM AUTHOR]

Background: The oral systemic efficacy of lotilaner (Credelio™, Elanco) was evaluated against Demodex spp. in naturally infested dogs with generalized demodicosis. Methods: In this study, 10 dogs with clinical signs of generalized demodicosis and positive for Demodex spp. mites based on skin scrapings were assigned to a single group orally treated with lotilaner (minimum dose of 20 mg/kg) on Days 0, 28 and 56. Results: For lotilaner-treated dogs, pre-treatment mite counts based on skin scrapings performed at five different sites were reduced by > 99.9% (P < 0.0001) up to 56 days after the first and second monthly doses. No live mites were detected after Day 56 out to and including Day 84 post-treatment for 100% efficacy of each dog's Demodex mite infestation. Nine of 10 dogs were 100% mite-free from Day 28 (first evaluation) through Day 84 (end of study) and live mites were only found once on one dog (Day 56) following treatment with lotilaner. All dogs in the lotilaner-treated group showed marked improvement in the clinical signs of demodicosis and there were no drug associated adverse events. A marked improvement in hair re-growth was observed in all the dogs from 6 weeks following initiation of treatment. Conclusions: In this study lotilaner administered at a minimum oral dose of 20 mg/kg was highly effective in reducing and eliminating live mite counts in dogs with natural infestations of Demodex spp. [ABSTRACT FROM AUTHOR]

Background: Dogs worldwide are at risk of Babesia spp. infections. Preventive efficacy of lotilaner tablets (Credelio™, Elanco) against Babesia canis was evaluated in two studies. Methods: Sixteen dogs in Study 1 and 12 dogs in Study 2, all seronegative and polymerase chain reaction (PCR) negative for B. canis, were randomized to a sham-treated control group or a lotilaner (20-43 mg/kg) treatment group, administered on Day 0 (Study 1: n = 8/group; Study 2: n = 6/group). Dogs were each infested with 50 Dermacentor reticulatus, a percentage of which (Study 1: 8.0-30.0%; Study 2: 12.2%) were infected with B. canis, in Study 1 on Days 2, 7, 14, 21 and 28, and in Study 2 on Day 28. Ticks were removed and counted on Day 30 in Study 1, and Day 34 in Study 2. Blood was collected for Babesia detection via smear, PCR and immunofluorescence assay (IFA) in Study 1 on Day 2, then approximately weekly through Day 56, and in Study 2 at weekly intervals between Days 28 to 49, and on Days 63 and 91. Additional samples were collected from dogs with body temperature > 39.4 °C (measured three times weekly, from Days 7 to 56 in Study 1 and from Days 35 to 56 in Study 2) and positive for B. canis on blood smear. Dogs with confirmed infections were rescue-treated, removed from the study and, in Study 1, replaced. Results: Across both studies B. canis infection of ticks ranged between 8.0-30.0%. In Study 1, all control dogs were positive for B. canis on blood smear and PCR on Day 10 and IFA on Day 21; on Day 21 seven of eight replacement control dogs were B. canis-positive; no replacement dogs were B. canis-positive following tick removal on Day 30. In Study 2, all control dogs were B. canis-positive on Day 56. All lotilaner-treated dogs remained B. canis-negative at all assessments in both studies. Conclusion: Lotilaner efficacy was 100% in preventing establishment of B. canis infection, despite post-treatment challenge with infected ticks on Days 2, 7, 14, 21 and 28. [ABSTRACT FROM AUTHOR]

Background: Lotilaner (Credelio™, Elanco), a novel isoxazoline, is a systemic insecticide and acaricide that is rapidly absorbed following oral administration to dogs and has a half-life of 30 days. As part of a development program, studies were undertaken to investigate lotilaner's initial and sustained efficacy and speed of kill against fleas. Methods: Four studies were conducted to evaluate the onset of lotilaner's speed of flea knockdown at the time of treatment, and to determine the sustained speed of flea kill (SOK) up to 35 days post-treatment. Each study assessed one or two specific time points (4, 6, 8 and 12 h) post-treatment and following weekly re-infestations. In each study, dogs were randomised to a lotilaner or an untreated group based on pre-administration flea counts, and before treatment were infested with adult Ctenocephalides felis. Dogs randomised to a lotilaner group received a single treatment on Day 0, at the minimum recommended dose rate of 20 mg/kg, 30 (± 5) minutes after being fed. Efficacy was calculated using geometric, and arithmetic mean flea counts in treated versus untreated groups. Results: On Day 0, lotilaner efficacy was 89.9% at 4 h, 99.2% at 6 h, 99.9% at 8 h, and 100% at 12 h post-treatment. At each weekly assessment, lotilaner efficacy at 4 h remained at > 97%, at 8 h remained at > 99%, and at 12 h remained at 100% through Day 35. Across all studies, there were no treatment-related adverse events. Conclusion: Lotilaner's rapid flea knockdown immediately following treatment and sustained SOK through 35 days post-treatment offers a new solution for helping to eliminate the health risks that accompany flea infestations on dogs. The consistency of the rapid, sustained flea SOK demonstrated in these studies generates confidence that monthly use of lotilaner in dogs can be valuable in disrupting the flea life cycle in a contaminated environment, and that newly acquired fleas will die quickly, thereby reducing the discomfort of flea bites. The sustained lotilaner SOK also provides confidence that there will be no "end-of-dose" resurgence in flea burdens with the potential accompanying consequence of flares in flea-bite hypersensitivity. [ABSTRACT FROM AUTHOR]

Background: Amblyomma cajennense is the main vector of Rickettsia rickettsii which causes Brazilian spotted fever. This adult tick preferably infests horses and capybaras, but has low host specificity during its immature stages, thus posing a threat to humans and dogs. In this study, the efficacy of sarolaner (Simparic™/Simparica®, Zoetis) when administered once orally to dogs at 2 mg/kg was evaluated against induced infestations of A. cajennense nymphs for up to 35 days after treatment. Methods: Based on pretreatment tick counts, 20 dogs were randomly allocated to treatment with sarolaner (Simparic™) dosed at 2 mg/kg of body weight or a placebo on Day 0 of the study. Artificial infestations were performed using laboratory raised A. cajennense nymphs on study days -2, 5, 12, 19, 26 and 33. Efficacy was determined at 48 h post-treatment or post-infestation at each time point relative to the counts for dogs that received placebo. Results: There were no adverse reactions to treatment. A single dose of sarolaner (Simparic™) provided 100% efficacy on study days 2, 7 and 14; and = 99.6% on days 21, 28 and 35. Geometric mean live tick counts for sarolaner were significantly lower than those for placebo on all days (P < 0.0001). Conclusions: Under the conditions of the present study, sarolaner (Simparic™) administered once orally at 2 mg/kg provided 100% efficacy against existing infestations and = 99.6% efficacy within 48 h against weekly challenges of A. cajennense for at least 35 days after treatment. [ABSTRACT FROM AUTHOR]

Background: The Australian paralysis tick, Ixodes holocyclus, causes paralysis predominantly in dogs and cats in the Eastern coastal regions of Australia. Rapid onset of effect of a parasiticide is critical to minimize the deleterious effects of these tick infestations, especially tick paralysis caused by the salivary neurotoxin. The speed of kill of a novel orally administered isoxazoline parasiticide, sarolaner chewable tablets (Simparica®), against I. holocyclus on dogs was evaluated and compared with afoxolaner (NexGard®) for 5 weeks after a single oral dose. Methods: Twenty-four (24) dogs were randomly allocated to treatment with either placebo, sarolaner (label dose of 2 to 4 mg/kg as per dosing table), or afoxolaner (label dose of 2.7 to 6.9 mg/kg) based on pre-treatment body weights. Following artificial infestation on Day -1, dogs were examined and live ticks counted at 8, 12, 24 and 48 h after treatment on Day 0, and at 12, 24 and 48 h after subsequent re-infestations on Days 7, 14, 21, 28 and 35. Efficacy was determined at each time point relative to counts for placebo dogs based on geometric means. Results: At 8 and 12 h time points on Day 0, sarolaner-treated dogs had significantly lower geometric mean tick counts compared to the dogs treated with afoxolaner (P ≤ 0.0303). Efficacy of sarolaner against an existing infestation was 86.2 and 96.9% compared with that of afoxolaner which had efficacy of 21.3 and 85.0% at 8 and 12 h time points, respectively. Against subsequent weekly re-infestations at 12 h time points, treatment with sarolaner resulted in significantly lower geometric mean tick counts than afoxolaner-treated dogs on all days (P ≤ 0.0077) with the efficacy ranging from 60.2 to 92.2%, compared to 5.8 to 61.0% in the afoxolaner-treated dogs. Against subsequent weekly re-infestations at the 24 h time points on Days 22 and 36, efficacy of sarolaner was significantly higher at 99.2 and 97.9%, respectively, compared with afoxolaner which had efficacy of 92.4 and 91.9% (P ≤ 0.0356). At the 48 h time points following each of the five weekly re-infestations, the mean efficacy results of sarolaner and afoxolaner treated dogs were similar on most occasions. There were no adverse reactions to treatments. Conclusions: In this controlled laboratory evaluation, a single dose of sarolaner had a significantly faster speed of kill against an existing infestation of I. holocyclus, than afoxolaner at 8 and 12 h post-treatment. The rapid and consistent kill of ticks provided by sarolaner within 24 h after a single oral dose and following weekly re-infestations over 35 days suggests this treatment will provide highly effective, rapid and reliable control of ticks over the entire treatment interval, thereby minimizing the risk of tick paralysis in dogs. [ABSTRACT FROM AUTHOR]

The efficacy of oral afoxolaner plus milbemycin oxime combination chewables against induced gastrointestinal nematode infections in dogs was evaluated in six separate studies. Two studies were performed to evaluate the efficacy of the product against Toxocara canis , two studies evaluated the efficacy against Toxascaris leonina , one study evaluated the efficacy against Ancylostoma braziliense , and one study evaluated the efficacy against Ancylostoma caninum. In the A. caninum study, the efficacy of milbemycin oxime alone and afoxolaner alone was also evaluated. Dogs in all studies were inoculated with infective eggs or larvae and confirmed to have patent infections based on a fecal examination prior to allocation to study group and treatment. Each study utilized a randomized block design with blocks based on pre-treatment body weight. All dogs were assigned to blocks based on body weight, and then each dog within a block was randomly assigned to treatment group. There were two groups of 10 dogs each in the T. canis, T. leonina , and A. braziliense studies: 1) an untreated (control) group and 2) a group treated with afoxolaner plus milbemycin oxime chewables (NexGard Spectra ® , Merial). This group was treated at a dose as close as possible to the minimum effective dose of afoxolaner and milbemycin oxime (2.5 mg + 0.5 mg per kg body weight, respectively) once on Day 0 using whole chews. There were four groups of 10 dogs each in the A. caninum study: 1) untreated (control), 2) NexGard Spectra ® as described above, 3) milbemycin oxime alone (dose of at least 0.5 mg per kg of body weight) and 4) afoxalaner alone (dose of at least 2.5 mg per kg body weight). For parasite recovery and counts, dogs were euthanized humanely and necropsied seven days after treatment. The efficacy of the afoxolaner plus milbemycin oxime combination was ≥98% against T. canis, ≥95.8% against T. leonina, and 90.2% against A. braziliense. Efficacy of the combination against A. caninum was 99.7%, while the efficacy of milbemycin oxime alone was 99.6% and the efficacy of afoxolaner alone was 2.1%. Dogs treated with afoxolaner plus milbemycin oxime chewables had significantly (p ≤ 0.0002) fewer nematodes than the untreated controls in all studies. There were no adverse events or other health problems that were related to treatment with Nexgard Spectra ® in these studies. The results of these controlled studies demonstrate the high efficacy of the afoxolaner plus milbemycin oxime chewables against a broad range of canine intestinal nematode infections. [ABSTRACT FROM AUTHOR]

Background: The lone star tick, Amblyomma americanum, infests dogs and cats in North America and transmits the pathogens Ehrlichia chaffeensis and Ehrlichia ewingii, which cause monocytic and granulocytic ehrlichiosis in dogs and humans, and Cytauxzoon felis which causes cytauxzoonosis in cats. A parasiticide's speed of kill is important to minimize the direct deleterious effects [related to blood-feeding] of tick infestation and reduce the risk of transmission of tick-borne pathogens. In this study the speed of kill of sarolaner (Simparica™ Chewables) administered monthly for 3 months against A. americanum on dogs was evaluated and compared with a single dose of fluralaner (Bravecto®) for 13 weeks. Methods: Based on pretreatment tick counts, 24 dogs were randomly allocated to treatment with placebo or sarolaner at the label rate (2 to 4 mg/kg) on Days 0, 30 and 60 or with fluralaner (25 to 56 mg/kg) once according to manufacturer's instructions on Day 0. Dogs were examined and live ticks counted at 8, 12, and 24 h after treatment and subsequent re-infestations on Days 14, 28, 42, 58, 76 and 90. Acaricidal efficacy was determined at each time point relative to counts for placebo dogs. Results: Monthly oral doses of sarolaner provided > 95 % efficacy within 24 h of treatment, and consistently provided > 70 % efficacy against subsequent re-infestations with ticks within 24 h over the entire treatment period. Significantly more live ticks were recovered from fluralaner-treated dogs than from sarolaner-treated dogs at 24 h after re-infestation from Day 42 onwards. At 24 h, efficacy of fluralaner was = 20 % from Day 42 to the end of the study on Day 90. There were no adverse reactions to treatment. Conclusions: In this controlled laboratory evaluation, monthly treatment with sarolaner provided consistent efficacy against A. americanum with > 70 % of ticks killed within 24 h after a single oral dose over the duration of the study. Monthly treatment with sarolaner consistently killed significantly more ticks within 24 h than a single dose of fluralaner from 6 weeks after initial treatment. [ABSTRACT FROM AUTHOR]

The efficacy of sarolaner (Simparica™, Zoetis) was evaluated against Demodex spp. in dogs with generalized demodicosis and against Otodectes cynotis (otodectic mange) in dogs with induced infestations. In the first study, 16 dogs with clinical signs of generalized demodicosis and positive for Demodex spp. mites were randomly assigned to treatment with either sarolaner (2 mg/kg) orally on Days 0, 30 and 60, or topical imidacloprid (10 mg/kg) plus moxidectin (2.5 mg/kg) solution every 7 days from Day 0 to Day 81. For sarolaner-treated dogs, pretreatment mite counts were reduced by 97.1% at 14 days and 99.8% by 29 days after the first dose, with no live mites detected thereafter. Weekly imidacloprid plus moxidectin resulted in 84.4 and 95.6% reduction at these two time points, respectively, with no mites detected from Day 74 on. All dogs in both groups showed marked improvement in the clinical signs of demodicosis. In the second study, 32 dogs with induced infestations of O. cynotis were randomly assigned (eight per group) to oral sarolaner (2 mg/kg) as a single treatment on Day 0 or as a two dose regime (Days 0 and 30), or a placebo group for each of the dose regimes. Sarolaner administered at 2 mg/kg as a single oral dose resulted in a 98.2% reduction at Day 30 and two doses of sarolaner, administered one month apart, resulted in a 99.5% reduction in ear mites at Day 60 compared to placebo controls. There were no treatment related adverse events in either study. In these studies, sarolaner at an oral dose of 2 mg/kg was highly effective in reducing the live mite counts associated with a natural infestation of Demodex spp. and an induced infestation of O. cynotis . In addition, the Demodex -infested dogs showed a marked improvement in the clinical signs of generalized demodicosis. [ABSTRACT FROM AUTHOR]

The efficacy of the novel isoxazoline, sarolaner (Simparica™) was investigated in dogs with clinical signs consistent with sarcoptic mange and harbouring natural infestations of Sarcoptes scabiei . One placebo-controlled laboratory study and one multi-centred field study with a commercial comparator containing imidacloprid/moxidectin (Advocate ® spot-on) were conducted. Oral or topical treatments were administered on Days 0 and 30. Up to 10 skin scrapings were taken for the assessment of S. scabiei infestations from each dog before treatment and on Days 14, 30, 44 and 60 in the laboratory study, and on Days 30 and 60 in the field study. In the laboratory study, efficacy was calculated based on the percent reduction of mean live mite counts compared to the placebo group. In the field study parasitological cure rate (% dogs free of mites) was determined and non-inferiority of sarolaner to the control product was assessed. In the laboratory study 44 mixed breed dogs were enrolled in four batches. Due to decreasing mite counts in the placebo treated dogs, immunosuppression with dexamethasone (0.4 mg/kg three times per week for two weeks) was initiated in all dogs on study at that time (n = 6) and those subsequently enrolled (n = 14). In the field study, dogs were enrolled in a 2:1 ratio (sarolaner:comparator); 79 dogs were assessed for efficacy and safety, and an additional 45 dogs were assessed for safety only. There were no treatment related adverse events in either study. In the laboratory study, no mites were found on any sarolaner-treated dogs 14 days after the first treatment except for one dog that had a single mite on Day 44. In the field study, the parasitological cure rate was 88.7% and 100% in the sarolaner group and 84.6% and 96.0% in the imidacloprid/moxidectin group, on Days 30 and 60, respectively. Statistical analysis showed that sarolaner was non-inferior to imidacloprid/moxidectin at both time points. The clinical signs of sarcoptic mange, including hair loss, papules, pruritus, erythema, and scaling/crusting improved throughout the study. Sarolaner was safe, achieved 100% reduction in the numbers of S. scabiei detected and resulted in marked improvement of the clinical signs of sarcoptic mange in dogs following two monthly oral administrations. [ABSTRACT FROM AUTHOR]

The efficacy of sarolaner (Simparica™, Zoetis) to prevent transmission primarily of Borrelia burgdorferi and secondarily of Anaplasma phagocytophilum from infected wild-caught Ixodes scapularis to dogs was evaluated in a placebo-controlled laboratory study. Twenty-four purpose-bred laboratory Beagles seronegative for B. burgdorferi and A. phagocytophilum antibodies were allocated randomly to one of three treatment groups: placebo administered orally on Days 0 and 7, or sarolaner at 2 mg/kg administered orally on Day 0 (28 days prior to tick infestation) or on Day 7 (21 days prior to tick infestation). On Day 28, each dog was infested with approximately 25 female and 25 male wild caught adult I. scapularis that were determined to have prevalence of 57% for B. burgdorferi and 6.7% for A. phagocytophilum by PCR. In situ tick counts were conducted on Days 29 and 30. On Day 33, all ticks were counted and removed. Acaricidal efficacy was calculated based on the reduction of geometric mean live tick counts in the sarolaner-treated groups compared to the placebo-treated group for each tick count. Blood samples collected from each dog on Days 27, 49, 63, 77, 91 and 104 were tested for the presence of B. burgdorferi and A. phagocytophilum antibodies using the SNAP ® 4Dx ® Plus Test, and quantitatively assayed for B. burgdorferi antibodies using an ELISA test. Skin biopsies collected on Day 104 were tested for the presence of B. burgdorferi by bacterial culture and PCR. Geometric mean live tick counts for placebo-treated dogs were 14.8, 12.8, and 19.1 on Days 29, 30, and 33, respectively. The percent reductions in mean live tick counts at 1, 2, and 5 days after infestation were 86.3%, 100%, and 100% for the group treated with sarolaner 21 days prior to infestation, and 90.9%, 97.1%, and 100% for the group treated with sarolaner 28 days prior to infestation. Geometric mean live tick counts for both sarolaner-treated groups were significantly lower than those for the placebo group on all count days ( P < 0.0001). There were no adverse reactions to treatment with sarolaner. Transmission of B. burgdorferi to all eight placebo-treated dogs was confirmed by positive antibody (6 of 8 dogs), PCR (7 of 8 dogs), and/or culture (7 of 8 dogs). Similarly, transmission of A. phagocytophilum was confirmed by the presence of antibodies in four placebo-treated dogs. In contrast, treatment with a single dose of sarolaner prevented transmission of B. burgdorferi from infected ticks to dogs infested 21 or 28 days after treatment as demonstrated by negative antibody, PCR, and culture results. Prevention of transmission of A. phagocytophilum was demonstrated by negative antibody results in all sarolaner-treated dogs. [ABSTRACT FROM AUTHOR]

The novel isoxazoline ectoparasiticide, sarolaner, was identified during a lead optimization program for an orally-active compound with efficacy against fleas and ticks on dogs. The aim of the discovery program was to identify a novel isoxazoline specifically for use in companion animals, beginning with de novo synthesis in the Zoetis research laboratories. The sarolaner molecule has unique structural features important for its potency and pharmacokinetic (PK) properties, including spiroazetidine and sulfone moieties. The flea and tick activity resides in the chirally pure S-enantiomer, which was purified to alleviate potential off-target effects from the inactive enantiomer. The mechanism of action was established in electrophysiology assays using CHO-K1 cell lines stably expressing cat flea ( Ctenocephalides felis ) RDL (resistance-to-dieldrin) genes for assessment of GABA-gated chloride channel (GABACls) pharmacology. As expected, sarolaner inhibited GABA-elicited currents at both susceptible (CfRDL-A285) and resistant (CfRDL-S285) flea GABACls with similar potency. Initial whole organism screening was conducted in vitro using a blood feeding assay against C. felis. Compounds which demonstrated robust activity in the flea feed assay were subsequently tested in an in vitro ingestion assay against the soft tick, Ornithodoros turicata . Efficacious compounds which were confirmed safe in rodents at doses up to 30 mg/kg were progressed to safety, PK and efficacy studies in dogs. In vitro sarolaner demonstrated an LC 80 of 0.3 μg/mL against C. felis and an LC 100 of 0.003 μg/mL against O. turicata . In a head-to-head comparative in vitro assay with both afoxolaner and fluralaner, sarolaner demonstrated superior flea and tick potency. In exploratory safety studies in dogs, sarolaner demonstrated safety in dogs ≥ 8 weeks of age upon repeated monthly dosing at up to 20 mg/kg. Sarolaner was rapidly and well absorbed following oral dosing. Time to maximum plasma concentration occurred within the first day post-dose. Bioavailability for sarolaner was calculated at >85% and the compound was highly protein bound (>99.9%). The half-life for sarolaner was calculated at 11–12 days. Sarolaner plasma concentrations indicated dose proportionality over the range 1.25–5 mg/kg, and these same doses provided robust efficacy (> 99%) for ≥35 days against both fleas ( C. felis ) and multiple species of ticks ( Rhipicephalus sanguineus , Ixodes ricinus and Dermacentor reticulatus ) after oral administration to dogs. As a result of these exploratory investigations, sarolaner was progressed for development as an oral monthly dose for treatment and control of fleas and ticks on dogs. [ABSTRACT FROM AUTHOR]

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 (2 mg/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 24 h 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 8 h 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 12 h, and 100% efficacy was achieved at 24 h 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 24 h after re-infestation at least through Day 28. [ABSTRACT FROM AUTHOR]

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 48 h 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 48 h. 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 2 mg/kg, resulted in excellent efficacy within 48 h 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. [ABSTRACT FROM AUTHOR]

Four studies were conducted to evaluate the speed of kill, effect on egg production, and efficacy in a simulated infested-home environment of a novel isoxazoline, sarolaner (Simparica™, Zoetis), against fleas on dogs. Individually identified and housed, purpose-bred Beagles were used in each study and were allocated randomly to groups based on pretreatment parasite counts. In two speed of kill studies, groups of dogs infested with 100 fleas prior to treatment were treated orally with placebo or sarolaner tablets providing the minimum dose of 2 mg/kg and then re-infested with fleas weekly for five weeks post-treatment. Comb counts were conducted to determine the numbers of viable fleas at one to three, four, eight and 12 h after treatment and each subsequent infestation. In the egg production study, sarolaner- and placebo-treated dogs were similarly challenged with fleas and at 48 h after each infestation the dogs were housed for 20 h in cages allowing the collection and counting of all flea eggs produced during this period. Collected eggs were incubated to evaluate hatch and development to adults. The last study used dogs housed in a flea-infested simulated-home environment. Dogs were allocated to treatment with either placebo or sarolaner tablets providing a dose of 2 mg/kg once a month for three treatments. Flea infestations were assessed by comb counts (fleas were replaced on the dogs) on Days 14, 30, 44, 60, 74 and 90. The speed of kill studies demonstrated that a single 2 mg/kg oral dose of sarolaner started killing fleas within three to four hours after treatment or subsequent re-infestations for up to a month, and achieved ≥98% control of fleas by eight hours after treatment or re-infestation for 28 days. In the study to assess effects on flea reproduction, a single oral treatment of sarolaner resulted in the complete cessation of egg-laying for 35 days. This rapid kill of fleas and inhibition of reproduction were confirmed in a simulated-home environment where the existing infestations were reduced by >95% within two weeks of the first treatment and eliminated from the dogs after two monthly doses. [ABSTRACT FROM AUTHOR]

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 2 mg/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 24 h 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 24 h after dosing, with only a single live C. felis found on one dog on Day 1. Similarly, control of flea challenges was achieved within 24 h after infestation throughout the 35 day 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 2 mg/kg provided highly effective treatment of existing C. felis infestations and persistent control of C. felis on dogs for 35 days after treatment. Efficacy equivalent to that seen with C. felis was confirmed against C. canis and a known insecticide-tolerant strain of C. felis . [ABSTRACT FROM AUTHOR]

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 5.0 mg/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 48 h after treatment and after each subsequent infestation at 24 h for fleas and 48 h for ticks. The lowest dose of sarolaner (1.25 mg/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 2.5 mg/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 (0.625 mg/kg) providing >95% efficacy through Day 43. Efficacy against D. variabilis on Day 35 was >95% at 1.25 and 2.5 mg/kg, whereas the 0.625 mg/kg dose gave only 61.4% efficacy. Amblyomma spp. were the least susceptible ticks; efficacy of the 1.25 mg/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 4.0 mg/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 2.0 mg/kg dose ( P > 0.05) at any time point. The 2.0 mg/kg dose was superior to the 1.0 mg/kg on Day 14 ( P = 0.0086) and as efficacy for 1.0 mg/kg declined below 90% at Day 28, a single 1 mg/kg dose would not provide a full month of tick control. Thus, 2.0 mg/kg was selected as the sarolaner dose rate to provide flea and tick control for at least one month following a single oral treatment. [ABSTRACT FROM AUTHOR]

The efficacy and safety of a novel isoxazoline parasiticide, sarolaner (Simparica™), for the control of fleas on dogs was evaluated in a randomized, controlled clinical study conducted in 19 general veterinary practices throughout the United States. Four hundred and seventy nine (479) dogs from 293 households were enrolled. Each household was randomly assigned to treatment with either sarolaner oral tablets (Simparica™, Zoetis) at the proposed label dose or an approved comparator product at the label dose (spinosad, Comfortis ® , Elanco). Dogs were dosed by their owners at home on Day 0 and on approximately Days 30 and 60. Dogs were examined at the clinics for general health, flea and tick infestation, and clinical signs of flea allergy dermatitis (FAD) at the initial visit and Days 14, 30, 60 and 90. Blood was collected for clinical pathology at screening and Day 90. Sarolaner was well-accepted by dogs with the majority of flavored chewable tablets (91.5%) accepted free choice, by hand or in food. Geometric mean live flea counts were reduced by >99% at the first time measured (14 days) after initiation of treatment and continued to reduce through the study. Treatment success (proportion of dogs with ≥90% reduction in fleas) for the sarolaner-treated dogs was superior to that for spinosad-treated dogs at Days 14 and 30 and non-inferior on Days 60 and 90 ( P ≤ 0.025) The rapid reduction in flea infestations resulted in a similar rapid resolution of the clinical signs associated with FAD. Sarolaner chewable tablets were well tolerated with no treatment related adverse reactions. Most of the clinical signs reported were consistent with allergies and dermatitis or sporadic occurrences of conditions commonly observed in the general dog population. A wide variety of concomitant medications, including many commercially available heartworm preventatives and other anthelmintic drugs, were administered to study dogs and all were well tolerated. Sarolaner administered orally to provide a minimum dosage of 2.0 mg/kg (range 2–4 mg/kg) once monthly for three consecutive treatments was safe and effective in the treatment and prevention of natural infestations of fleas and resulted in a substantial improvement of clinical signs associated with FAD. [ABSTRACT FROM AUTHOR]

The efficacy of single oral treatment of sarolaner (Simparica™, Zoetis), a novel isoxazoline compound, was evaluated against four tick species known to commonly infest dogs in Europe. Eight laboratory studies were conducted using adult purpose-bred Beagle dogs. In each study, 16 animals were randomly allocated to one of two treatment groups based on pre-treatment host-suitability tick counts. Dogs were infested with 50 unfed adult Dermacentor reticulatus (two studies), Ixodes hexagonus (three studies), Ixodes ricinus (two studies) or Rhipicephalus sanguineus (one study) ticks on Days −2, 5, 12, 19, 26 and 33. On Day 0, dogs were treated orally with placebo or sarolaner tablets providing the minimum dose of 2.0 mg/kg bodyweight and tick counts were conducted 48 h after treatment and after each subsequent weekly re-infestation. There were no treatment-related adverse reactions in any of the studies. Dogs in the placebo-treated group maintained tick infestations throughout the studies. Geometric mean live tick counts were significantly ( P ≤ 0.0001) lower in the sarolaner-treated group compared to the tick counts in the placebo group at all time-points. A single oral administration of sarolaner resulted in 100% efficacy against existing infestations of all tick species except R. sanguineus, for which the efficacy was 99.7%, within 48 h. Efficacy against weekly re-infestations was ≥97.5% for all tick species for 35 days. Thus, a single dose of sarolaner administered orally at the minimum dosage of 2 mg/kg, resulted in ≥99.7% efficacy within 48 h against existing tick infestations, and in ≥97.5% efficacy against weekly re-infestations, for at least 35 days after treatment. These studies confirmed that administration of the minimum dose of sarolaner will provide treatment of existing infestations and give at least one month of control against re-infestation by the common tick species affecting dogs in Europe. [ABSTRACT FROM AUTHOR]

Background: Ticks are common ectoparasites that infest dogs globally. Acaricides with rapid and sustained speed of kill are critical to control infestations and to reduce the risk of disease transmission. This study evaluated the speed of kill for 5 weeks after a single dose of orally administered SimparicaTM(sarolaner) against induced infestations with Dermacentor reticulatus on dogs, compared to Advantix®Spot-on solution for dogs (imidacloprid + permethrin). Methods: Twenty four dogs were randomly allocated to treatment witheither a placebo tablet, a sarolaner tablet (at 2 to 4 mg/kg) or with Advantix® as per label instructions. Dogs were treated on Day 0 and tick counts were performed in situ at 8 and 12 hours and with removal of the ticks at 24 hours after treatment and subsequent re-infestations on Days 7, 14, 21, 28 and 35. Acaricidal efficacy was determined at each time point relative to live tick counts from the placebo-treated dogs. Results: Based on arithmetic (geometric) mean tick counts, the efficacy of sarolaner was ≥75.6 % (89.6 %) within 8 hours of treatment and tick counts were significantly lower than placebo and imidacloprid + permethrin-treated dogs (P < 0.0001), while imidacloprid + permethrin had no significant reduction (P ≥ 0.3990) at 8 or 12 hours after treatment. Sarolaner killed all ticks on the dogs within 24 hours after treatment, while imidacloprid + permethrin efficacy was only 48.1 %. After weekly re-infestations sarolaner significantly reduced the tick counts versus placebo within 8 hours on Days 7, 14 and 35 (P ≤0.0239), and at 12 hours and 24 hours (P ≤0.0079) until Day 35.Sarolaner efficacy was ≥95.8 % within 24 hours for 35 days. Significantly more live ticks (P ≤0.0451) were recovered from imidacloprid + permethrin-treated dogs than from sarolaner-treated dogs at 24 hours after infestation on all days. There were no sarolaner-related adverse reactions during the study. Conclusions: This study demonstrated that SimparicaTM had a faster and more consistent speed of kill against D. reticulatus compared to Advantix®. The rapid and consistent efficacy within 24 hours for 5 weeks after a single oral dose of SimparicaTM provides effective and reliable control of D. reticulatus and reduces the risk of transmission of tick-borne diseases. [ABSTRACT FROM AUTHOR]

Background: Rhipicephalus sanguineus is the most widely distributed tick species infesting dogs worldwide, which may cause discomfort to the host and transmit diseases. Acaricides with a rapid and sustained speed of kill are thus important to prevent infestation and to reduce the risk of disease transmission. In this study, the speed of kill of a monthly administered SimparicaTM(sarolaner) treatment against induced infestations with R. sanguineus on dogs was evaluated and compared with a single dose of Bravecto®(fluralaner) for 95 days after the initial treatment. Methods: Twenty four dogs were randomly allocated to treatment and were treated witheither placebo or sarolaner (at 2 to 4 mg/kg) on Days 0, 30 and 60 or with fluralaner (at 25 to 56 mg/kg) once on Day 0. Tick counts were performed in situ 8 and 12 h and with removal of the ticks 24 h after treatment and subsequent re-infestations on Days 14, 28, 44, 56, 74, 90 and 95. Acaricidal efficacy was determined at each time point relative to the placebo group. Results: Both products significantly reduced live ticks within 8 h after treatment against an existing infestation with R. sanguineus, and killed all ticks on all dogs within 24 h. After re-infestation, sarolaner provided ≥98.5 % reduction within 24 h on all days except Days 74 and 95 (P < 0.0001), compared tofluralaner which provided ≥95.5 % reduction until Day 44. Geometric mean live tick counts for sarolaner were significantly lower (P ≤0.0415) at 24 h than those for fluralaner on all days, except on Days 0, 14 and 28 (P ≥ 0.0678). There were no treatment-related adverse reactions observed during the study. Conclusions: When dosed at monthly intervals for 3 consecutive months, SimparicaTM has a faster and more consistent speed of kill against R. sanguineus than a single oral dose of Bravecto® for which efficacy decreased after Day 44. [ABSTRACT FROM AUTHOR]

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 [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: The black-legged (or deer) tick, Ixodes scapularis, commonly infests dogs and cats in North America and is the main vector for the pathogen that causes Lyme disease in dogs and humans. The speed of kill of a parasiticide is critical to minimize the direct and deleterious effects of tick infestation and especially to reduce the risk of tick-borne pathogen transmission. In this study, speed of kill of a novel orally administered isoxazoline parasiticide, sarolaner chewable tablets (Simparica™), against I. scapularis on dogs was evaluated and compared with afoxolaner (NexGard®) for five weeks after a single oral dose. Methods: Twenty four dogs were randomly allocated to treatment with either placebo, sarolaner (2 to 4 mg/kg), or afoxolaner (2.5 to 6.8 mg/kg) based on pretreatment tick counts. 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 >99 % efficacy within 24 h of treatment and >95 % against subsequent weekly re-infestations of ticks consistently to Day 35. For the earlier time points, sarolaner significantly reduced tick counts versus placebo from Day 0 to Day 21 at 8 and 12 h, and on Day 35 at 12 h (P ≤ 0.0174), while afoxolaner was only significantly lower at 8 h on Days 0 and 14 (P ≤ 0.0309), and at 12 h on Day 0 only (P < 0.0001). Significantly more live ticks were recovered from afoxolaner-treated dogs than from sarolaner-treated dogs at 24 h after infestation from Day 14 to Day 35 (P ≤ 0.0278). At 24 h, efficacy (based on geometric mean counts) of afoxolaner declined to less than 80 % from Day 21 through the end of the study, while efficacy for sarolaner was >95 % for 35 days. There were no adverse reactions to treatments. Conclusions: In this controlled laboratory evaluation, sarolaner had a faster speed of kill against I. scapularis than afoxolaner. This was noticeably more pronounced towards the end of the monthly treatment period. The rapid and consistent kill of ticks provided by sarolaner within 24 h after a single oral dose and re-infestation over 35 days suggests this treatment will provide highly effective and reliable control of ticks over the entire treatment interval, and should reduce the risk of tick-borne diseases, including Lyme disease whose agent is vectored by I. scapularis. [ABSTRACT FROM AUTHOR]

Background Fluralaner, a novel isoxazoline, has both acaricidal and insecticidal activity through potent blockage of GABA- and L-glutamate-gated chloride channels. This study investigated the in vitro and in vivo effects of fluralaner exposure on flea (Ctenocephalides felis) reproduction. Methods Blood spiked with sub-insecticidal fluralaner concentrations (between 0.09 and 50.0 ng/mL) was fed to fleas for 10 days using a membrane system. Cessation of reproduction in exposed fleas was assessed using flea survival, egg hatchability, and control of oviposition, pupae, and flea emergence. Fluralaner efficacy for in vivo Ctenocephalides (C.) felis control on dogs was assessed using a simulated flea-infested home environment. During a pre-treatment period, dogs were infested twice on days -28 and -21 with 100 adult unfed fleas to establish a thriving population by day 0 of the study. On day 0, one group of dogs was treated with fluralaner (Bravecto™; n = 10), while another group served as negative control (n = 10). Following treatment, dogs were infested three times with 50 fleas on days 22, 50 and 78 to simulate new infestations. Live flea counts were conducted weekly on all dogs for 12 weeks starting 1 day before treatment. Results Fluralaner potently inhibited flea reproduction capacity in vitro. Oviposition ceased completely at concentrations as low as 25.0 ng/mL. While no ovicidal effect was observed, fluralaner exerted a larvicidal effect at exceptionally low concentrations (6.25 ng/mL). In the simulated flea-infested home environment, flea-control efficacy on fluralaner-treated dogs was >99% at every time point measured for 12 weeks. No adverse events were observed in fluralaner-treated dogs. Conclusions Fluralaner completely controls egg laying, larval development and flea reproduction even at sub-insecticidal concentrations. Oral treatment of dogs with fluralaner is highly effective for eliminating fleas in a simulated flea-infested home environment. [ABSTRACT FROM AUTHOR]

Abstract: 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. [Copyright &y& Elsevier]

Abstract: 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 48h post-treatment (Day 2) as well as 48h following each infestation on Days 9, 16, 23, and 30. Afoxolaner, administered at an average dose of 2.7mg/kg bodyweight (range 2.5–2.9mg/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. [Copyright &y& Elsevier]

Background Fluralaner, a new molecular entity of the isoxazoline class, has potent insecticidal and acaricidal activity and can be safely administered orally to dogs. Methods A randomized, investigator-blinded, multi-centered field study compared the flea- and tickcontrol efficacy for dogs over a 12-week period with either a single oral dose of Bravecto™ (fluralaner) formulated as a chewable tablet or with three sequential topical FrontlineTM (fipronil) treatments. Individual dogs were the experimental unit for ticks and households were the experimental unit for fleas. A total of 108 tick-infested dogs were treated with Bravecto™ (fluralaner) and 54 tick-infested dogs were treated with FrontlineTM (fipronil). Dogs in 115 flea-infested households received Bravecto™ (fluralaner) and dogs in 61 fleainfested households received Frontline™ (fipronil). Flea and tick counts were conducted on all dogs at weeks 2, 4, 8, and 12 following initial treatment and efficacy was calculated as the mean percent reduction in tick or flea count at each time point compared with the mean pretreatment initiation count for each treatment group. Additionally, the percentages of tickfree and flea-free households were determined. Results At weeks 2, 4, 8, and 12, Bravecto™ (fluralaner) flea-control efficacy in treated households was 99.2%, 99.8%, 99.8%, and 99.9% respectively, while Frontline™ (fipronil) efficacy was 94.1%, 93.0%, 96.0%, and 97.3%, respectively. Bravecto™ (fluralaner) tick-control efficacy on treated dogs at weeks 2, 4, 8, and 12 was 99.9%, 99.9%, 99.7%, and 100%, respectively, and FrontlineTM (fipronil) tick efficacy was 97.6%, 93.8%, 100%, and 100%, respectively. Of dogs showing clinical flea allergy dermatitis (FAD) signs at the study start, 85.7% in the Bravecto™ (fluralaner)-treated group and 55.6% in the Frontline™ (fipronil)-treated group were evaluated at each time point as showing no clinical signs of FAD until study completion. Conclusions Bravecto™ (fluralaner) administered once orally to dogs in a chewable tablet was highly effective for 12 weeks against fleas and ticks on privately-owned dogs and was significantly non-inferior (ticks) and superior (fleas) in comparison with topical FrontlineTM (fipronil) administered 3 times sequentially. [ABSTRACT FROM AUTHOR]