RESUMO
BACKGROUND: Studies show that the novel isoxazoline, lotilaner (Credelio™ CAT; Elanco Animal Health), which is administered orally to cats, provides rapid and sustained flea kill for least 1 month following administration with a wide safety margin. A clinical trial was undertaken to confirm its efficacy, impact on flea allergy dermatitis (FAD) and safety under field conditions. METHODS: A total of 343 cats were enrolled in the study at 11 veterinary clinics in the USA. Upon inclusion, cat households were randomized at a ratio of 2:1 to receive lotilaner tablets at the recommended dose (minimum 6 mg/kg) or a topical formulation containing fipronil + S-methoprene (Frontline® Plus for cats; Boehringer Ingelheim), administered per label. Owners were dispensed treatments for administration on days 0, 30 and 60; all household cats were administered the same treatment. Flea counts were made on primary cats (1 cat per household) on days 0 (pre-treatment), 30, 60 and 90. Flea allergy dermatitis was assessed on days 30, 60 and 90 for all cats with signs of FAD on day 0. Lotilaner-treated cats were also assessed for their acceptance of oral tablet administration by the pet owner, and safety was assessed for all cats in both groups. RESULTS: Lotilaner efficacy was 98.3, 99.9 and 99.9% on days 30, 60 and 90, respectively, while the efficacy of fipronil + S-methoprene was 61.6, 75.4 and 84.7%, respectively (P < 0.0001, within both groups and all days). Flea counts were significantly lower in the lotilaner group than in the fipronil + S-methoprene group (P < 0.0001) on each assessment day. On day 90, 98.3% of lotilaner-treated cats and 28.8% of fipronil + S-methoprene-treated cats were free of fleas. Owners successfully administered 99.5% of tablets to their cats. Total FAD score was reduced significantly following treatment in both groups by day 30 (lotilaner: P < 0.0001; fipronil + S-methoprene: P = 0.0041) and continued to decrease following multiple treatments. Total FAD scores were also significantly lower in the lotilaner group than in the fipronil + S-methoprene group on day 90 (P = 0.0006 for FAD total score). Pruritus scores were significantly lower in the lotilaner group on all assessment days. CONCLUSION: A single lotilaner treatment, administered by the pet owner, was > 98% efficacious in reducing flea counts within 30 days. Three consecutive monthly lotilaner treatments resulted in nearly 100% reduction in flea infestation. In the evaluations of flea counts, number of cats free from fleas and pruritus FAD score, lotilaner was shown to be superior to fipronil + S-methoprene at all time points. Lotilaner was more efficacious than fipronil + S-methoprene and was associated with greater reduction in FAD signs. Lotilaner flavored tablets were well accepted by cats. Adverse reactions were mild and infrequent, confirming the safety of lotilaner tablets in client-owned cats.
Assuntos
Doenças do Gato/tratamento farmacológico , Ctenocephalides/efeitos dos fármacos , Infestações por Pulgas/tratamento farmacológico , Infestações por Pulgas/veterinária , Inseticidas/uso terapêutico , Oxazóis/uso terapêutico , Comprimidos/uso terapêutico , Tiofenos/uso terapêutico , Administração Oral , Animais , Doenças do Gato/parasitologia , Gatos , Feminino , Hospitais Veterinários , Inseticidas/administração & dosagem , Inseticidas/farmacologia , Masculino , Mastigação , Propriedade , Oxazóis/administração & dosagem , Oxazóis/farmacologia , Animais de Estimação/parasitologia , Distribuição Aleatória , Pele/efeitos dos fármacos , Pele/parasitologia , Tiofenos/administração & dosagem , Tiofenos/farmacologia , Resultado do Tratamento , Estados UnidosRESUMO
BACKGROUND: The ixodid tick Amblyomma cajennense (sensu lato) complex, widespread throughout South and Central America, is also present in Mexico, Texas and Florida. As a vector of Rickettsia rickettsii, and potentially of other pathogens, infestations with A. cajennense present a substantial health risk to humans, dogs and other mammals. Oral administration of lotilaner flavored chewable tablets (CredelioTM, Elanco) to dogs was previously shown to rapidly provide killing activity of infesting ticks. This study investigated lotilaner's efficacy against A. cajennense (s.l.). METHODS: Twenty purpose-bred Beagles (10 male and 10 female) were ranked by Day -5 burdens of nymphal A. cajennense (s.l.) and randomized to either treatment with lotilaner or to a sham-treated control group. On Day 0, dogs were fed within approximately 30 min prior to oral lotilaner administration at as close as possible to 20 mg/kg, the minimum dose rate. For efficacy assessments, tick counts were completed 48 h post-treatment or 48 h after experimental challenge infestations with 200 nymphal A. cajennense (s.l.) on Days -7, -2, 7, 14, 21 and 28. RESULTS: Tick infestations in the control group dogs ranged from a low of 43 to 95, with the average infestation remaining above 25% at each assessment, thereby meeting the requirement for efficacy comparison with the treated group. Lotilaner efficacy was 100% within 48 h post-treatment, and at nine days post-treatment. Efficacy was greater than 99% at all subsequent assessments through Day 30. No treatment-related adverse events were observed. CONCLUSION: The results demonstrate that lotilaner, administered orally to dogs at a minimum dose of 20 mg/kg is well tolerated, provides rapid reduction of existing A. cajennense (s.l.) tick infestations, and provides sustained residual protection for at least 30 days against subsequent infestation by A. cajennense (s.l.).
Assuntos
Acaricidas/farmacologia , Acaricidas/uso terapêutico , Doenças do Cão/tratamento farmacológico , Ixodidae/efeitos dos fármacos , Controle de Ácaros e Carrapatos/métodos , Infestações por Carrapato/veterinária , Acaricidas/administração & dosagem , Administração Oral , Animais , Doenças do Cão/parasitologia , Cães , Feminino , Masculino , Ninfa/efeitos dos fármacos , Infestações por Carrapato/tratamento farmacológico , Infestações por Carrapato/parasitologia , Resultado do TratamentoRESUMO
BACKGROUND: Throughout Japan, Korea and China, Haemaphysalis longicornis ticks are vectors of Babesia gibsoni, which causes severe and progressive anemia in dogs. This study evaluated the efficacy of a single administration of lotilaner flavored chewable tablets (CredelioTM) against experimental canine H. longicornis infestations. METHODS: Twenty-two healthy Beagles were ranked in descending order of counts of H. longicornis completed 48 h after challenge on Day -7. The 16 dogs with the highest live tick counts were blocked into pairs and within pairs randomized to either lotilaner-treatment at a minimum dose rate of 20 mg/kg or sham-treated controls. Treatment was administered within 30 ± 5 min following feeding on Day 0. Infestations with 50 unfed adult H. longicornis were completed on Days -2, 7, 14, 21, 28 and 35. Elizabethan collars were placed for 48 (± 2) h after each infestation and a T-shirt was placed on each dog to facilitate attachment. Ticks were counted in situ 12 and 24 h post-treatment and counted and removed after an additional 24 h (48 h after treatment) and 48 h after each post-treatment infestation. Dogs were sedated for tick challenges and counts. Live attached ticks on each dog were counted for efficacy assessments. Lotilaner was considered effective if the average tick attachment rate in the control group was at least 20%, if there was a statistically significant difference (P < 0.05) in mean tick counts between treated and control groups, and if the lotilaner-treated group had a calculated efficacy of at least 90%. RESULTS: Average control group retention of the H. longicornis challenge exceeded 20% at each assessment. Lotilaner started killing H. longicornis ticks quickly, achieving 57.4% efficacy within 12 h. At 48 h post-treatment, and following each subsequent infestation, between-group differences in mean H. longicornis counts were significant (P < 0.0001). From 48 h post-treatment, through the final assessment on Day 37, lotilaner efficacy remained greater than 95%, including on Day 37 when efficacy was 98.4%. CONCLUSION: Lotilaner, administered to dogs orally at a minimum dose rate of 20 mg/kg is well tolerated, provides rapid reduction of existing H. longicornis tick infestations, and provides sustained residual protection for at least 35 days.
Assuntos
Doenças do Cão/parasitologia , Ixodidae/efeitos dos fármacos , Infestações por Carrapato/veterinária , Acaricidas/uso terapêutico , Animais , Doenças do Cão/tratamento farmacológico , Cães , Feminino , Masculino , Controle de Ácaros e Carrapatos , Infestações por Carrapato/tratamento farmacológico , Infestações por Carrapato/parasitologiaRESUMO
BACKGROUND: From three days following host attachment, the Australian paralysis tick, Ixodes holocyclus, secretes a neurotoxin that annually causes paralysis in approximately 10,000 domestic pets. Lotilaner, a novel isoxazoline formulated in a chewable flavoured tablet (CredelioTM), produces rapid onset of acaricidal activity in dogs, with an efficacy duration of at least one month. Two studies were performed to determine the efficacy of lotilaner against I. holocyclus infestations over 3 months. METHODS: Both studies included 16 dogs, ranked according to I. holocyclus counts on Day -5 (from infestations on Day -8) and blocked into pairs. One dog in each pair was randomized to be a sham-treated control, the other to receive lotilaner at a minimum dose rate of 20 mg/kg on Day 0. Dogs were dosed in a fed state. Infestations were performed in both studies on Days -8 (to determine the tick carrying capacity of each dog) -1, 28, 56, 70, 77 and 84, and additionally in Study 1 on Day 91, in Study 2 on Days 14 and 42. In Study 1, ticks were counted and assessed as alive or dead at 24, 48 and 72 h post-initial infestation and post-subsequent re-infestations. In study 2, ticks were counted at 24, 48 and 72 h post-dosing or post-re-infestation. Efficacy was determined by the percent reduction in live attached tick counts in the lotilaner group compared to control. RESULTS: Within 48 h post-treatment in Study 1 and within 72 h post-treatment in Study 2 all lotilaner-group dogs were free of live ticks. By 72 h post-infestation, efficacy in Study 1 remained at 100% through Day 87, except on Day 31 when a single tick was found on one dog, and through Day 59 in Study 2. Efficacy exceeded 95% through the final assessment in each study (Days 94 and 87 in Studies 1 and 2, respectively). CONCLUSION: These results demonstrate that lotilaner quickly kills existing I. holocyclus infestations. By providing 95.3-100.0% protection through at least 87 days post-treatment, lotilaner can be a valuable tool in reducing the risk of tick paralysis in dogs.
Assuntos
Doenças do Cão/tratamento farmacológico , Inseticidas/uso terapêutico , Isoxazóis/uso terapêutico , Ixodes/efeitos dos fármacos , Infestações por Carrapato/veterinária , Paralisia por Carrapato/veterinária , Administração Oral , Animais , Austrália/epidemiologia , Doenças do Cão/parasitologia , Cães , Feminino , Inseticidas/administração & dosagem , Inseticidas/efeitos adversos , Isoxazóis/administração & dosagem , Isoxazóis/efeitos adversos , Laboratórios/estatística & dados numéricos , Masculino , Neurotoxinas/metabolismo , Neurotoxinas/uso terapêutico , Comprimidos , Infestações por Carrapato/tratamento farmacológico , Infestações por Carrapato/epidemiologia , Paralisia por Carrapato/tratamento farmacológico , Paralisia por Carrapato/epidemiologia , Paralisia por Carrapato/parasitologia , Fatores de TempoRESUMO
BACKGROUND: Lotilaner is approved for dogs as a chewable tablet formulation. It has separately been developed for oral administration in cats (Credelio™ chewable tablets for cats) to meet the need for an easy to use, safe and rapidly effective parasiticide and as an alternative to topical products. This paper describes two pivotal laboratory studies assessing the efficacy and speed of kill of lotilaner in cats against Ctenocephalides felis fleas following a single oral administration, at the minimum recommended dose rate of 6 mg/kg. METHODS: Two GCP (Good Clinical Practice), blinded, randomized, negative-controlled, parallel-groups, laboratory studies were performed. In both studies, lotilaner was administered once, per os, at the minimum recommended dose of 6 mg/kg. Study 1 evaluated the efficacy of lotilaner tablets for cats against adult C. felis in experimentally infested cats, 24 h after treatment and after new weekly infestations, until day 35. Study 2 evaluated the speed of kill of lotilaner against C. felis, in cats, 8 and 12 h after treatment and after each subsequent weekly infestation, through day 35. In both studies, for each assessed time point, animals were randomized 1:1 to a lotilaner-treated or a contemporaneous negative control group of 8 cats each. RESULTS: In both studies, the infestation in the control groups was adequate at all assessment times. In Study 1, efficacy at 24 h was 100% at all time points. In Study 2, efficacy was ≥ 97.4% at the 8 h and ≥ 98.6% at the 12 h time point, through one month. Lotilaner was well tolerated, with no product-related adverse events reported. CONCLUSIONS: Lotilaner administered orally to cats at the minimum recommended dose rate of 6 mg/kg was effective as early as 8 hours post-administration and at 8 hours after subsequent weekly infestations of adult C. felis for at least one month. The product was well-tolerated.
Assuntos
Ctenocephalides , Doenças do Cão/prevenção & controle , Infestações por Pulgas/veterinária , Inseticidas , Isoxazóis , Administração Oral , Animais , Gatos , Doenças do Cão/tratamento farmacológico , Cães , Infestações por Pulgas/tratamento farmacológico , Infestações por Pulgas/prevenção & controle , Segurança , Comprimidos , Resultado do TratamentoRESUMO
BACKGROUND: Lotilaner, approved for dogs as a chewable tablet formulation, has separately been developed for oral use in cats (CredelioTM chewable tablets for cats), to meet the need for an easy to use, safe and rapidly effective parasiticide. It is a valid cat- and owner-friendly alternative to topical products. This manuscript describes three pivotal laboratory studies assessing the efficacy and speed of kill of lotilaner in cats against Ixodes ricinus ticks following a single oral administration, at a dose rate close to 6 mg/kg. METHODS: In Studies 1 and 2, efficacy and safety were evaluated 48 h after treatment and post-treatment weekly infestations in 16 cats, against untreated controls, for 35 days. In Study 3, efficacy and safety were assessed in 8 lotilaner-treated cats until Day 35, before and after 24 h incubation of the female live ticks removed from the animals 12, 18 and 24 h after dosing and subsequent weekly infestations. RESULTS: Efficacy was > 99% on days 23 and 37, and 100% on all other timepoints in Study 1. In Study 2 it was > 98% on Days 9 and 37, and 100% on all other days. In Study 3, on Day 0, lotilaner was > 90% efficacious, pre- and post-incubation at all time-points. On Day 7, at 12 hours after infestation, efficacy was 100%, pre- and post-incubation. On Day 14, there was a 66.5% reduction in geometric mean live tick counts in treated cats compared to controls, increasing, after incubation, to 94.4%. Afterwards, efficacy decreased below 90% while tick counts in the treated groups remained significantly lower compared to controls. At 18 hours, lotilaner was ≥ 90% efficacious through Day 37, increasing to 100% at 24 hours, on all study days, with the exception of Day 28 (98.9 and 99.1% pre- and post-incubation, respectively). There were no treatment-related adverse events. CONCLUSIONS: At the minimum dose rate of 6 mg/kg, lotilaner was efficacious against I. ricinus ticks. In addition, lotilaner was effective against this tick within 12 hours of treatment, reaching 100% efficacy within 24 hours. Lotilaner sustained a rapid kill of newly infesting I. ricinus through 35 days. By quickly killing ticks that infest cats, lotilaner has the potential to contribute to the reduction of tick-borne pathogens transmission.
Assuntos
Acaricidas/administração & dosagem , Antiparasitários/administração & dosagem , Doenças do Gato/tratamento farmacológico , Isoxazóis/administração & dosagem , Ixodes , Infestações por Carrapato/veterinária , Administração Oral , Animais , Gatos , Feminino , Masculino , Infestações por Carrapato/tratamento farmacológico , Fatores de Tempo , Resultado do TratamentoRESUMO
BACKGROUND: Lotilaner is a new isoxazoline developed as an oral ectoparasiticide for cats and dogs. Its safety, rapid killing onset of action and sustained speed of fleas and ticks kill for a minimum of one month after administration, were demonstrated in a number of laboratory studies in cats. This study was performed to demonstrate the efficacy and safety of lotilaner flavored chewable tablets for cats (Credelio™, Elanco) in controlling fleas under field conditions in European countries. METHODS: Seventeen veterinary practices in France and Spain, located in high flea prevalence regions, participated in the study. Households with a maximum of three cats and two dogs were randomized 2:1 to a lotilaner (minimum dose rate 6 mg/kg) or a topical fipronil/(S)-methoprene combination (Frontline Combo® Spot-on Cats, Merial) group (administered according to label). In each household, efficacy against fleas and flea allergy dermatitis (FAD) signs were assessed in one primary cat (bearing a minimum of five fleas on Day 0) while safety was evaluated in all cats. There were 121 households included in the lotilaner and 61 in the fipronil/(S)-methoprene groups, respectively. Treatments were administered by the cats' owners on Day 0. Flea counts and FAD assessments were made on Days 0, 14, and 28. Efficacy calculations were based on geometric mean percent reductions of live flea counts versus baseline pre-treatment counts. RESULTS: Lotilaner efficacy was 97.2 and 98.1% on Days 14 and 28, respectively. Corresponding efficacy for fipronil/(S)-methoprene was 48.3 and 46.4%. Lotilaner was superior to fipronil/(S)-methoprene at all post-Day 0 assessments and over the whole study period (P < 0.0001). At every post-administration evaluation, at least 81% of lotilaner-treated cats were flea-free as opposed to 25% in the fipronil/(S)-methoprene group. Lotilaner improved or eliminated clinical signs of FAD, including pruritus. Both products were well tolerated. CONCLUSIONS: Under field conditions in Europe, lotilaner flavored chewable tablets for cats displayed an efficacy against fleas higher than 97%; clinical signs of FAD were improved or eliminated. Lotilaner tablets were safe and provided superior flea control to fipronil/(S)-methoprene.
Assuntos
Doenças do Gato/tratamento farmacológico , Infestações por Pulgas/veterinária , Inseticidas/uso terapêutico , Isoxazóis/uso terapêutico , Sifonápteros , Animais , Gatos , Dermatite/tratamento farmacológico , Dermatite/parasitologia , Dermatite/veterinária , Combinação de Medicamentos , Feminino , Infestações por Pulgas/tratamento farmacológico , França , Inseticidas/efeitos adversos , Isoxazóis/efeitos adversos , Masculino , Metoprene/efeitos adversos , Metoprene/uso terapêutico , Pirazóis/efeitos adversos , Pirazóis/uso terapêutico , Espanha , Resultado do TratamentoRESUMO
BACKGROUND: There is a continuing need for novel approaches to tick infestations treatment and control in cats. Lotilaner, an isoxazoline with rapid onset of action, has proven its efficacy against ticks in laboratory studies. A study was undertaken to confirm lotilaner's efficacy and safety in client-owned cats, at the minimum dose of 6.0 mg/kg, against the most common ticks infesting cats in Europe. METHODS: Twenty clinics in Germany, Hungary and Portugal participated in the study. Households with no more than three cats were randomized 2:1 to a lotilaner or fipronil group. The first household cat with at least three live, attached ticks was the primary cat. Treatments were dispensed on days 0, 28 and 56 for owner administration. Tick counts were performed on days 0, 7, 14, 21, 28, 42, 56, 70 and 84 (primary cats) and supplementary cats were assessed for safety only, on days 28, 56 and 84. Efficacy was assessed by comparing mean day 0 live attached tick counts with subsequent counts. RESULTS: Most frequently retrieved ticks were Ixodes ricinus, Rhipicephalus sanguineus and Dermacentor reticulatus, with Ixodes hexagonus also present. In the lotilaner group (n = 112) efficacy (based on geometric mean tick counts) was between 98.3-100%. For fipronil (n = 57), efficacy was between 89.6-99.6%, with live attached ticks present on some cats at all time points. Mean tick counts in lotilaner-treated cats were significantly lower than in fipronil-treated cats on days 21, 28, 42 and 56 (P < 0.05). The mean percent efficacy over all post-enrolment visits was 99.6% and 96.4% (lotilaner and fipronil group, respectively), (P < 0.0001). Lotilaner was superior to fipronil for efficacy averaged over all time points (P < 0.0001) and on individual assessment days (day 14 to 70, P < 0.0394); it was non-inferior to fipronil on the other days. Owners successfully administered all treatments, and both products were well tolerated. CONCLUSIONS: CredelioTM was effective and safe for the treatment of tick infestations in client-owned cats. Efficacy lasted one month and lotilaner was superior to fipronil on most assessment days. Cure rates ranged between 94.5-100% for lotilaner and 68.4-98.2% for fipronil.
Assuntos
Acaricidas/uso terapêutico , Doenças do Gato/tratamento farmacológico , Isoxazóis/uso terapêutico , Ixodidae , Infestações por Carrapato/veterinária , Acaricidas/efeitos adversos , Animais , Gatos , Feminino , Alemanha , Hungria , Isoxazóis/efeitos adversos , Masculino , Portugal , Pirazóis/efeitos adversos , Pirazóis/uso terapêutico , Infestações por Carrapato/tratamento farmacológico , Resultado do TratamentoRESUMO
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.
Assuntos
Ctenocephalides/efeitos dos fármacos , Doenças do Cão/tratamento farmacológico , Infestações por Pulgas/veterinária , Inseticidas/uso terapêutico , Administração Oral , Animais , Doenças do Cão/parasitologia , Cães , Feminino , Infestações por Pulgas/tratamento farmacológico , Inseticidas/administração & dosagem , Masculino , Fatores de TempoRESUMO
BACKGROUND: With the geographical expansion of tick species and increased recognition of pathogens they transmit, there is a requirement for safe and rapidly effective control measures for dogs. Lotilaner, a novel isoxazoline, is rapidly absorbed following administration of a flavored chewable tablet formulation (Credelio™), providing at least 98% efficacy for at least 1 month following assessments at 48 h post-treatment, and following subsequent challenges. A study was conducted to determine the speed with which lotilaner kills ticks. METHODS: From 38 dogs, the 32 with the highest Ixodes ricinus counts from a Day -4 infestation were randomized among four groups: two groups were untreated controls, two received lotilaner tablets at a minimum dose rate of 20 mg/kg. Infestations with I. ricinus were performed on Days -2, 7, 14, 21, 28 and 35. Counts were completed 4 and 8 h post-treatment (Day 0), and 8 and 12 h following subsequent infestations. All live ticks were incubated for 24 h following removal from study dogs. RESULTS: At 4 h post-treatment, there was a 69.8% reduction in geometric mean live tick counts in treated dogs compared to controls. After incubation, the reduction increased to 97.2%. At 8 h after treatment, pre- and post-incubation reductions were 99.2 and 100%, respectively. Following post-treatment challenges, post-incubation efficacy through Day 28 at 8 and 12 h was at least 94.3 and 98.0%, respectively, and was 85.7 and 94.2% at 8 and 12 h after the Day 35 challenge. Mean live tick counts in the lotilaner groups were significantly lower than in the control groups at all assessments through Day 35 at 8 (t (7) ≥ 9, P < 0.0001, Days 0 to 28; t (7) = 3.54, P ≤ 0.0095, Day 35) and 12 h post-treatment and after subsequent infestations (t (7) ≥ 10, P < 0.0001, all days). There were no treatment-related adverse events. CONCLUSION: Lotilaner at a minimum dose rate of 20 mg/kg began to kill ticks on dogs within 4 h of treatment and efficacy was 100% within 8 h. Lotilaner sustained a rapid kill of newly infesting I. ricinus through 35 days. By quickly killing ticks that infest dogs, lotilaner has potential to help limit the transmission of tick-borne pathogens.
Assuntos
Acaricidas/uso terapêutico , Doenças do Cão/tratamento farmacológico , Ixodes/efeitos dos fármacos , Infestações por Carrapato/veterinária , Acaricidas/administração & dosagem , Administração Oral , Animais , Doenças do Cão/parasitologia , Cães , Feminino , Masculino , Infestações por Carrapato/parasitologia , Fatores de Tempo , Resultado do TratamentoRESUMO
BACKGROUND: There is a continuing need for novel approaches to tick control in dogs. One such approach lies in the ability of lotilaner (Credelio™), an isoxazoline with a rapid onset of action, to provide sustained efficacy against ticks. Two studies were undertaken to confirm lotilaner's efficacy, at the minimum dose rate of 20 mg/kg, against the three most common tick species in Europe. METHODS: In each of two studies, 16 Beagle dogs, at least 6 months old, were ranked and blocked by tick counts from infestations placed approximately 1 week before treatment. Within blocks, dogs were randomized to receive either lotilaner flavoured chewable tablets at as close as possible to, but not less than the minimum dose rate of 20 mg/kg, or to be sham-treated controls. Study 1 assessed lotilaner efficacy against concurrent infestations with 50 (± 6) Rhipicephalus sanguineus and 70 (± 6) Ixodes ricinus; Study 2 infestations were with 50 (± 2) Dermacentor reticulatus. Infestations were performed on Day -2 with counts on Day 2, 48 (± 2) hours post-treatment. Post-treatment infestations were performed on Days 7, 14, 21, 28 and 35, and ticks were counted 48 (±2) hours post-infestations. Efficacy was determined by the percent reduction in mean live tick counts. RESULTS: Control group infestations for each tick species were adequate for assessing lotilaner efficacy at all assessment times. On Day 2 no live ticks were found on any lotilaner-treated dog. For subsequent counts, in Study 1 lotilaner was 100% effective in eliminating live I. ricinus and R. sanguineus on all but two occasions for each tick; on each of those occasions efficacy was sustained at greater than 98.0%. In Study 2, except for a single unattached live tick found on Day 16, efficacy against D. reticulatus was 100% at every post-treatment assessment. CONCLUSION: The high and sustained efficacy against the three common species of ticks in Europe, R. sanguineus, I. ricinus and D. reticulatus, demonstrates that lotilaner can be a valuable tool in the treatment of canine tick infestations. Lotilaner flavoured chewable tablets were well tolerated and effectiveness was sustained through at least 35 days.
Assuntos
Acaricidas/uso terapêutico , Dermacentor/efeitos dos fármacos , Doenças do Cão/tratamento farmacológico , Infestações por Carrapato/veterinária , Carrapatos/efeitos dos fármacos , Acaricidas/administração & dosagem , Acaricidas/efeitos adversos , Animais , Doenças do Cão/parasitologia , Cães , Europa (Continente) , Feminino , Ixodes/efeitos dos fármacos , Masculino , Rhipicephalus sanguineus/efeitos dos fármacos , Controle de Ácaros e Carrapatos , Infestações por Carrapato/tratamento farmacológico , Infestações por Carrapato/parasitologia , Carrapatos/classificação , Fatores de TempoRESUMO
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.
Assuntos
Acaricidas/uso terapêutico , Babesiose/prevenção & controle , Babesiose/transmissão , Dermacentor/efeitos dos fármacos , Doenças do Cão/tratamento farmacológico , Infestações por Carrapato/veterinária , Acaricidas/administração & dosagem , Acaricidas/efeitos adversos , Animais , Babesia/genética , Babesia/fisiologia , Babesiose/sangue , Babesiose/tratamento farmacológico , Dermacentor/parasitologia , Doenças do Cão/parasitologia , Doenças do Cão/prevenção & controle , Doenças do Cão/transmissão , Cães , Reação em Cadeia da Polimerase , Infestações por Carrapato/tratamento farmacológico , Infestações por Carrapato/prevenção & controle , Infestações por Carrapato/transmissãoRESUMO
BACKGROUND: Effective control of tick infestations on dogs is important to reduce the risk of transmission of bacterial, viral, and protozoal pathogens. Laboratory studies were initiated to determine the efficacy of lotilaner against common ticks infesting dogs in the United States. METHODS: Eight studies investigated the efficacy of lotilaner against ticks. In two studies dogs were infested with both Dermacentor variabilis and Rhipicephalus sanguineus: one additional study was completed for each of these species. Two studies assessed infestations with Amblyomma americanum and two with Ixodes scapularis. In all studies, dogs were ranked and blocked by counts from pre-treatment infestations and randomly allocated, at least eight per group, to be treated orally with lotilaner (minimum dose rate 20 mg/kg), or to be untreated controls. Treatments were administered on Day 0, within 30 min after dogs were fed. In all studies, infestations were performed with 50 adult ticks on Days -2, 7, 14, 21 and 28, and also on Day 35 for R. sanguineus, D. variabilis and I. scapularis. Tick counts were completed 48 h after treatment or after each subsequent challenge. An adequate infestation was defined as at least 25% of the infestation dose recovered from each of at least six control animals at each evaluation. Efficacy calculations for the primary objective were based on geometric means. RESULTS: In all studies, lotilaner was 100% effective against existing infestations. For post-treatment assessments, on only two occasions did efficacy fall below 99%: in one D. variabilis study efficacy was 98.0% on Day 35 and in one I. scapularis study efficacy on Day 16 was 98.4%. Only mild and transient adverse events were observed, and none were considered to be related to treatment. CONCLUSION: Lotilaner was completely effective against existing infestations with four common species of ticks, D. variabilis, R. sanguineus, A. americanum and I. scapularis, that affect dogs in North America, with at least 4 weeks efficacy of 98.0% or more against subsequent challenge infestations. These results show that lotilaner is a highly effective isoxazoline that offers sustained efficacy against ticks through and beyond the one-month end-of-dose treatment interval.
Assuntos
Acaricidas/uso terapêutico , Dermacentor/efeitos dos fármacos , Doenças do Cão/tratamento farmacológico , Ixodidae/efeitos dos fármacos , Infestações por Carrapato/veterinária , Acaricidas/administração & dosagem , Acaricidas/efeitos adversos , Administração Oral , Animais , Dermacentor/parasitologia , Doenças do Cão/parasitologia , Cães , Feminino , Ixodes/efeitos dos fármacos , Ixodidae/classificação , Masculino , América do Norte/epidemiologia , Rhipicephalus sanguineus/efeitos dos fármacos , Infestações por Carrapato/tratamento farmacológico , Infestações por Carrapato/parasitologia , Fatores de TempoRESUMO
BACKGROUND: Oral administration of lotilaner flavoured chewable tablets (Credelio™, Elanco) to dogs has been shown to provide a rapid onset of killing activity of infesting ticks, with sustained efficacy for at least 35 days. A study was undertaken in Europe to confirm lotilaner's safety and anti-tick efficacy in client-owned dogs. METHODS: In this assessor-blinded study, dogs were enrolled at 19 clinics in Germany, Hungary and Portugal. Qualifying households with no more than three dogs were randomized in an approximate 2:1 ratio to a lotilaner or fipronil/(S)-methoprene (FSM) (Frontline® Combo Spot-on, Merial) treatment group. One household dog with at least three live attached ticks was the primary dog. Treatments were dispensed Days 0, 28 (± 2) and 56 (± 2) for owner administration to all household dogs. Tick counts were performed on primary dogs Days 7 (± 1), and ±2 days on Days 14, 21, 28, 42, 56, 70 and 84; supplementary dogs were assessed for safety ± 2 days on Days 28, 56 and 84. Efficacy was assessed by comparing mean Day 0 live attached tick counts with subsequent counts. RESULTS: The most frequently retrieved ticks were Ixodes ricinus, Dermacentor reticulatus and Rhipicephalus sanguineus (sensu lato), with Ixodes hexagonus also present. In the lotilaner group (n = 127) geometric mean tick count reductions were at least 98% from the first post-treatment visit (Day 7) through Day 56, when efficacy was 100%. For FSM (n = 68), efficacy remained at least 96% through Day 84, but at no point were all dogs free of live attached ticks. Mean counts in lotilaner-treated dogs were significantly lower than FSM-treated dogs on Days 7, 42, 70 and 84 (P < 0.05). Percent efficacy over all post-enrolment visits was 99.3 and 98.3% for lotilaner and FSM groups, respectively (t (190) = 2.23, P = 0.0268). Owners successfully administered all treatments, and both products were well-tolerated. CONCLUSION: Under European field conditions, lotilaner flavoured chewable tablets administered monthly, were > 98% effective in eliminating live ticks from the first post-treatment assessment (Day 7) through Day 56 and maintained 100% of dogs tick-free on Days 70 and 84. Lotilaner was safe, providing superior tick control to FSM administered according to the same schedule.
Assuntos
Acaricidas/uso terapêutico , Doenças do Cão/tratamento farmacológico , Ixodes/efeitos dos fármacos , Infestações por Carrapato/tratamento farmacológico , Acaricidas/administração & dosagem , Acaricidas/efeitos adversos , Administração Oral , Animais , Dermacentor/efeitos dos fármacos , Doenças do Cão/parasitologia , Cães , Europa (Continente) , Feminino , Masculino , Pirazóis/administração & dosagem , Pirazóis/efeitos adversos , Pirazóis/uso terapêutico , Rhipicephalus/efeitos dos fármacos , Comprimidos/administração & dosagem , Comprimidos/efeitos adversos , Infestações por Carrapato/parasitologia , Infestações por Carrapato/veterináriaRESUMO
BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.
Assuntos
Doenças do Cão/tratamento farmacológico , Infestações por Pulgas/veterinária , Inseticidas/efeitos adversos , Inseticidas/uso terapêutico , Sifonápteros/efeitos dos fármacos , Administração Oral , Animais , Doenças do Cão/parasitologia , Cães , Infestações por Pulgas/tratamento farmacológico , Infestações por Pulgas/parasitologia , Hospitais Veterinários , Inseticidas/administração & dosagem , Isoxazóis/administração & dosagem , Isoxazóis/efeitos adversos , Isoxazóis/uso terapêutico , Naftalenos/administração & dosagem , Naftalenos/efeitos adversos , Naftalenos/uso terapêutico , Comprimidos , Estados UnidosRESUMO
BACKGROUND: Lotilaner is a novel isoxazoline developed for oral administration to dogs. In laboratory studies, lotilaner was shown to be safe and to produce a rapid flea and tick knockdown, with a sustained speed of kill for at least a month post-treatment. A study was undertaken to demonstrate the efficacy, safety and palatability of three monthly doses of lotilaner flavoured chewable tablets (Credelio™, Elanco) in controlling fleas under field conditions in Europe. METHODS: Dogs were enrolled at 17 veterinary clinics across Germany, Hungary and Portugal. Qualifying households having no more than three dogs and one primary dog with at least five fleas was randomised 2:1 to a lotilaner (minimum dose rate 20 mg/kg) or a topical fipronil group (administered per label). There were 128 and 64 households allocated to the lotilaner and fipronil groups, respectively. Treatments were dispensed to owners on Days 0, 28 and 56; supplementary household dogs received the same treatment as the primary dog. Post-enrollment flea counts and flea allergy dermatitis (FAD) assessments were made on primary dogs on Days 14, 28, 56 and 84. Efficacy calculations were based on geometric mean percent reductions of live flea counts versus pre-treatment counts on Day 0. The safety and palatability of lotilaner tablets were also assessed. RESULTS: Lotilaner efficacy was 99.1, 99.5, 99.9 and 99.8% on Days 14, 28, 56 and 84, respectively. Corresponding reductions for fipronil were 93.4, 91.2, 94.4 and 97.0%. Lotilaner was superior to fipronil at all post-Day 0 assessments (t (186) ≥ 3.43, P ≤ 0.0007). At every post-treatment assessment, at least 90% of lotilaner-treated dogs were flea-free (98.4% on Day 84); fewer than 90% of fipronil group dogs were flea-free on the same time points. Lotilaner flavoured chewable tablets were palatable, and both products were well tolerated. Lotilaner alleviated or eliminated clinical signs of FAD, including pruritus. CONCLUSIONS: Under field conditions in Europe, lotilaner flavoured chewable tablets were greater than 99% effective in eliminating fleas from dogs at the first post-treatment assessment (Day 14). Efficacy was maintained through Day 84, with corresponding improvements in FAD. Lotilaner tablets were palatable and safe and provided superior flea control to fipronil.
Assuntos
Infestações por Pulgas/veterinária , Inseticidas/administração & dosagem , Inseticidas/efeitos adversos , Sifonápteros/efeitos dos fármacos , Administração Oral , Animais , Doenças do Cão/tratamento farmacológico , Doenças do Cão/parasitologia , Cães , Europa (Continente) , Feminino , Infestações por Pulgas/tratamento farmacológico , Infestações por Pulgas/parasitologia , Alemanha , Hospitais Veterinários , Hungria , Inseticidas/uso terapêutico , Masculino , Propriedade , Portugal , Pirazóis/administração & dosagem , Pirazóis/uso terapêutico , ComprimidosRESUMO
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.
Assuntos
Ctenocephalides/efeitos dos fármacos , Doenças do Cão/tratamento farmacológico , Infestações por Pulgas/veterinária , Inseticidas/administração & dosagem , Administração Oral , Animais , Doenças do Cão/parasitologia , Cães , Feminino , Infestações por Pulgas/tratamento farmacológico , Infestações por Pulgas/parasitologia , Inseticidas/sangue , Inseticidas/uso terapêutico , Masculino , Infestações por Ácaros/tratamento farmacológico , Comprimidos , Fatores de Tempo , Resultado do TratamentoRESUMO
Two libraries of enantiomerically pure imidazolium salts bearing an oxazoline unit were synthesized. Deprotonation of the imidazolium salts and complexation of the resulting oxazoline-carbene ligands to iridium(I) was achieved in one step by mixing the imidazolium salts with NaOtBu and [(eta(4)-cod)IrCl](2) in THF at room temperature. The air-stable complexes were purified by flash chromatography. All complexes were analyzed by two-dimensional (2D) NMR methods and one compound from each family was characterized by X-ray structure analysis. The two libraries of iridium complexes were successfully tested in the asymmetric hydrogenation of unfunctionalized and functionalized olefins. Enantioselectivities of up to 90 % ee were obtained with trans-alpha-methylstilbene. Upon complexation of imidazolium salt 15 p with R(1) = phenyl, C-H bond activation of the phenyl ring gave rise to iridium(III) complex 17, which was fully characterized by NMR spectroscopy and X-ray structure analysis. Complex 17 proved to be catalytically inactive in the hydrogenation.
Assuntos
Imidazóis/química , Irídio/química , Metano/análogos & derivados , Compostos Organometálicos/química , Oxazóis/química , Catálise , Técnicas de Química Combinatória , Cristalografia por Raios X , Hidrocarbonetos/química , Hidrogenação , Imidazóis/síntese química , Ligantes , Espectroscopia de Ressonância Magnética , Metano/química , EstereoisomerismoRESUMO
The determination of residual dipolar couplings (RDCs) by quantitative J spectroscopy methods such as Heteronuclear Single Quantum Correlation with Phase Encoded Coupling (HSQC-PEC) is prone to systematic errors that may be caused by differential attenuation during the conversion of orthogonal density operator components into observable terms. The attenuation may be caused by miscalibration of radio-frequency pulses and by relaxation effects. A simple method is presented that allows one to remove most of these systematic errors without losses in sensitivity or resolution.