Efficacy of selamectin in the treatment of naturally acquired cheyletiellosis in cats

The purpose of this study was to evaluate the efficacy of a topical formulation of selamectin in the treatment of cheyletiellosis in cats. Fifteen adult domestic cats from the same household with naturally occurring Cheyletiella sp. infestation were enrolled in the study. On each cat, 45 mg of selamectin was applied on days 0, 30, and 60. No other treatment or environmental decontamination was performed during the trial. On days 0, 30, 60, and 120, all cats were examined, epidermal debris was collected over the dorsal area of the body with flea combs for microscopic examination, and fecal flotations were done. Clinical signs had subsided by day 60 in all 15 cats and no signs of recurrence were apparent on follow-up 1 year later. All epidermal and fecal samples were negative by day 60. No adverse reactions were observed. Under the conditions of our study, topical selamectin was a practical and well-tolerated means of treatment for cheyletiellosis in cats.     

Efficacy and safety of topical administration of selamectin for treatment of ear mite infestation in rabbits

OBJECTIVE: To evaluate the efficacy and safety of topical administration of selamectin in rabbits naturally infested with Psoroptes cuniculi. DESIGN: Randomized controlled trial. ANIMALS: 48 mixed-breed domestic rabbits with active P. cuniculi mite populations and clinical ear lesions. PROCEDURES: Rabbits were randomly allocated to 1 of 6 treatment groups. On day 0, rabbits in groups 1 and 2 were given vehicle, rabbits in groups 3 and 4 were given selamectin at a dose of 6 mg/kg (2.7 mg/lb), and rabbits in groups 5 and 6 were given selamectin at a dose of 18 mg/kg (8.2 mg/lb). On day 28, rabbits in groups 2, 4, and 6 were given a second dose of vehicle or selamectin. Otoscopic examinations were performed and ear lesion size was measured weekly for 8 weeks. Quantitative viable mite counts were performed on day 56. RESULTS: On days 7 through 56, lesion sizes for all selamectin-treated groups were significantly lower than sizes for control groups; there were no significant differences in lesion sizes among selamectin-treated groups. All rabbits in the 2 control groups had viable adult P. cuniculi mites for the duration of the study, as determined by otoscopic examination, whereas all rabbits in the 4 selamectin-treated groups were free from P. cuniculi mites on days 7 through 56. No adverse reactions associated with selamectin treatment were observed. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that topical application of selamectin at a dose of 6 or 18 mg/kg can completely eliminate mites from rabbits naturally infested with P. cuniculi.     

Observations on topical ivermectin in the treatment of otoacariosis, cheyletiellosis, and toxocariosis in cats

The purpose of this study was to observe the efficacy of a topical pour-on formulation of ivermectin in the treatment of otoacariosis, cheyletiellosis, and toxocariosis in cats. Forty-five cats were treated. All cats received 2 to 4 topical applications of ivermectin on the skin between the shoulder blades in a narrow strip, 14 days apart. This practical treatment was effective in 96% (23/24) of cases of feline otoacariosis and in 100% (20/20) of cats with toxocariosis. All cats with cheyletiellosis (16/16) received 4 treatments and had resolution of clinical signs, but one Cheyletiella egg could still be found 45 days after the last treatment. The viability of this egg could not be evaluated, but the cats were still free of clinical signs on follow-up 6 months later. The treatment was well tolerated in all the animals. A few cats developed a transient small alopecic area and mild scaling at the site of application of the drug.     

Treatment of rabbit cheyletiellosis with selamectin or ivermectin: a retrospective case study

Background

A retrospective study of rabbits treated against cheyletiellosis was performed to evaluate the efficacy and safety of selamectin or ivermectin in clinical practice.

Methods

Medical records from 53 rabbits with microscopically confirmed Cheyletiella infestation were collected from two small animal clinics. The rabbits were divided into three groups, based on treatment protocols. Group 1 included 11 rabbits treated with ivermectin injections at 200–476 μg kg^-1 subcutaneously 2–3 times, with a mean interval of 11 days. In Group 2, 27 rabbits were treated with a combination of subcutaneous ivermectin injections (range 618–2185 μgkg^-1) and oral ivermectin (range 616–2732 μgkg^-1) administered by the owners, 3–6 times at 10 days interval. The last group (Group 3) included 15 rabbits treated with selamectin spot-on applications of 6.2–20,0 mgkg^-1, 1–3 times with an interval of 2–4 weeks. Follow-up time was 4 months–4.5 years.

Results

Rabbits in remission were 9/11 (81,8%), 14/27 (51,9%) and 12/15 (80,8%) in groups 1, 2 and 3, respectively.

Conclusion

All treatment protocols seemed to be sufficiently effective and safe for practice use. Though very high doses were used in Group 2 (ivermectin injections followed by oral administration), the protocol seemed less efficacious compared to ivermectin injections (Group 1) and selamectin spot on (Group 3), respectively, although not statistically significant. Controlled prospective studies including larger groups are needed to further evaluate efficacy of the treatment protocols.     

Evaluation of the comparative efficacy of selamectin against flea (Ctenocephalides felis felis) infestations on dogs and cats in simulated home environments

The comparative efficacy of monthly administration of selamectin or lufenuron against Ctenocephalides felis felis on dogs and cats was evaluated over a 5-month period in flea-infested environments. Twenty-four dogs and 32 cats were randomly allocated to receiving a topical treatment with selamectin or an oral administration of tablets containing lufenuron/milbemycin oxime (for dogs) or lufenuron only (for cats). Each product was administered in accordance with the manufacturer's label recommendations. Eight dogs and four cats served as untreated sentinels. Treatments were administered on days 0, 30, 60, 90, and 120. Each animal received an application of 100 fleas on days -28 and -21, and then weekly applications of 20 fleas from days 91 through 147. Flea comb counts were performed on day -6, and every 2 weeks after day 0. From day 29 (dogs) or day 44 (cats) to day 150, geometric mean flea counts for selamectin were < or =0.4. Mean flea counts for animals assigned to treatment with selamectin were significantly lower (P=0.0001) than for animals assigned to treatment with lufenuron at all assessments after day 0.     

Use of selamectin for the treatment of psoroptic and sarcoptic mite infestation in rabbits

Selamectin, a novel avermectin compound, was evaluated for its efficacy against naturally occurring infestations of Psoroptes cuniculi and Sarcoptes scabiei. A total of 42 New Zealand rabbits with psoroptic mange and 37 Angora rabbits with sarcoptic mange were used in the present study. On day 0, infested rabbits were treated topically with either selamectin at minimum dose of 6 mg kg(-1) (6-18 mg kg(-1) for New Zealand rabbits, n = 31 and 10-12 mg kg(-1) for Angora rabbits, n = 23) or vehicle only (control groups, n = 11 for New Zealand rabbits, n = 14 for Angora rabbits). The efficacy of selamectin was assessed both clinically and parasitologically by the presence or absence of viable mites. Rabbits were scraped for sarcoptic mites on days 7, 14, 28, 42 and 56 and had otoscopeic and/or microscopic examination for the detection of Psoroptes mites on days 7, 14, 42 and 56. Fisher's exact test was used to assess differences between the vehicle and selamectin treatment in the number of rabbits without mites (cure rates) on each assessment date. It was found that significantly fewer selamectin-treated rabbits had mites detected on skin scrapings (for S. scabiei) or otoscopeic and/or microscopic examination (for P. cuniculi) (P < 0.01) than the vehicle group. Results of the present study suggest that selamectin is effective against naturally infestations of P. cuniculi and S. scabiei in rabbits.     

P-23 Clinical and epidemiological characteristics of 153 cases of Sarcoptic acariosis in dogs

A randomized and controlled field study was performed in canine patients to evaluate the efficacy of selamectin in the treatment of naturally occurring Sarcoptes scabiei and Otodectes cynotis infestations in dogs. A total of 227 dogs from six veterinary practices in South Korea were included. Dogs were randomly assigned to treatment with selamectin or a positive-control product. Selamectin was administered as a unit dose providing a minimum of 6 mg/kg in a topical preparation applied to the skin in a single spot on days 0 and 30 [ S. scabiei ( n =  113) and O. cynotis ( n =  114)]. The presence of parasites was assessed before treatment and at 14, 30 and 60 days after the initiation of treatment. The animals were evaluated clinically at each assessment period. Based on skin scrapings, the efficacy of selamectin against S. scabiei infestations on dogs was >95% by day 30, and 100% by day 60. Against O. cynotis , selamectin eliminated mites in 100% of dogs by day 60. However, clinical signs of pruritus, erythema, scale, and crusted papules did not diminish concomittantly with resolution of S. scabiei in skin scrapings. The positive-control products achieved similar results. Therefore, selamectin was safe and effective against sarcoptic mange and ear mites in dogs.
Funding: Pfizer Animal Health.     

Efficacy of selamectin against experimentally induced and naturally acquired ascarid (Toxocara canis and Toxascaris leonina) infections in dogs

The efficacy of selamectin against adult ascarids was evaluated in eight controlled and masked studies in dogs. Three laboratory studies evaluated selamectin against experimentally induced infections of Toxocara canis; three laboratory studies evaluated selamectin against naturally acquired infections of T. canis; one laboratory study evaluated selamectin against naturally acquired infections of both T. canis and Toxascaris leonina; one field study evaluated selamectin against naturally acquired infections of ascarids (T. canis and/or T. leonina) in dogs presented as veterinary patients. Selamectin was administered topically to the skin of dogs in unit doses designed to deliver a minimum of 6mgkg(-1) (range, 6-12mgkg(-1)). In all studies, dogs were allocated randomly to treatment assignments (selamectin or vehicle control in laboratory studies: selamectin or reference product in the field study) on the basis of pretreatment fecal egg counts. For induced infections, there were significant reductions in geometric mean numbers of adult T. canis after a single application of selamectin (93.9-98.1%, P=0.0001), after two monthly applications (> or =88.3%, P< or =0.0001), and after three monthly applications (100%, P< or =0.0002). In the natural infection laboratory studies, when selamectin was administered twice at an interval of 30 days, the percentage reductions in geometric mean numbers of adult T. canis at necropsy were 84.6, 91.3, and 97.9%, and when selamectin was administered on days 0, 14, and 30, the percentage reductions were 91.1 and 97.6%. Geometric mean fecal T. canis egg counts were reduced by > or =92.9% (P< or =0.0067) at the end of the studies. In the field study, geometric mean fecal ascarid egg counts were reduced by 89.5 and 95. 5% (P=0.0001) for 14 and 30 days, respectively, after a single treatment with selamectin, and by 94.0% (P=0.0001) 30 days after the second treatment with selamectin. These reductions compared favorably with the egg count reductions from dogs treated with a reference product containing praziquantel, pyrantel embonate, and febantel. There were no adverse drug experiences or treatment-related mortalities during any of the studies. Selamectin, when administered topically in a unit dose providing a minimum dosage of 6mgkg(-1), was safe and effective against adult T. canis and T. leonina and in reducing the fecal excretion of T. canis eggs in dogs.     

Efficacy of selamectin against experimentally induced and naturally acquired infections of Toxocara cati and Ancylostoma tubaeforme in cats

The efficacy of selamectin against experimentally induced and naturally acquired infections of adult ascarids (Toxocara cati) and adult hookworms (Ancylostoma tubaeforme) was evaluated in five controlled studies in cats. Two studies evaluated the efficacy of selamectin against both ascarid (natural or induced) and hookworm (induced) infections; two studies evaluated the efficacy of selamectin against single natural infections of T. cati or A. tubaeforme; and the fifth study evaluated the efficacy of selamectin against induced infections of A. tubaeforme. Cats received selamectin topically in unit doses designed to deliver a minimum of 6mgkg(-1). Treatments were applied to the skin on each animal's back at the base of the neck in front of the scapulae. For experimentally induced infections, cats were inoculated orally with approximately 500 embryonated eggs of T. cati 56 days prior to treatment and/or approximately 150-250 larvae (L(3)) of A. tubaeforme 30 or 42 days prior to treatment. For both induced and naturally acquired infections, cats were allocated randomly to treatments (6-12 cats per treatment) on the basis of fecal egg counts to receive either selamectin or a vehicle containing the inert formulation ingredients. In all studies, adult worm counts were performed at necropsy 14 days after the last treatment administration. Against T. cati, a single application of selamectin provided a 100% reduction in the geometric mean number of adult worms for both experimentally induced and naturally acquired infections. Against A. tubaeforme, a single administration of selamectin provided a 99.4% reduction in the geometric mean number of adult worms in cats with natural infections, and an 84.7-99.7% reduction in adult worms in cats with induced infections.Two doses of selamectin administered at monthly intervals provided a 91.9% reduction in the geometric mean number of adult A. tubaeforme worms in cats with experimentally induced infections. The geometric mean numbers of adult worms (T. cati and A. tubaeforme) from selamectin-treated cats were significantly (P< or =0.0018) lower than for vehicle-treated cats in all studies. Thus, a single topical unit dosage providing a minimum dosage of 6mgkg(-1) selamectin was highly effective in the treatment of naturally acquired and experimentally induced infections of T. cati and A. tubaeforme in cats.     

Efficacy of selamectin against experimentally induced tick (Rhipicephalus sanguineus and Dermacentor variabilis) infestations on dogs

Seven controlled studies were conducted to investigate the efficacy of selamectin against weekly infestations of dogs with Rhipicephalus sanguineus and Dermacentor variabilis. Treatments (selamectin or vehicle alone) were applied topically at weekly, 2-week, or monthly intervals or in a "Monthly Plus" regimen (monthly treatment with an additional treatment at 14 days after the first treatment). Selamectin was supplied in unit dose tubes designed to deliver a minimum dosage of 6mgkg(-1). The studies ranged in duration from 37 to 90 days. Fifty adult ticks (+/-2) were applied approximately weekly, and tick counts were performed 3, 4, and 5 days after each infestation. The efficacy of selamectin was expressed as the percentage reduction in geometric mean tick counts on selamectin-treated dogs compared with those for dogs treated with the vehicle alone (negative-control). In one study, the engorgement of Dermacentor variabilis was assessed by weighing ticks after removal on the fifth day after each infestation. Weekly and 2-week interval treatments with selamectin provided efficacies against R. sanguineus of >89% across the entire study periods, with 100% efficacy being achieved from 21 days after the first dose and thereafter (study duration, 37 days for the weekly regimen and 44 days for the 2-week interval regimen). D. variabilis also was well controlled by the 2-week interval treatment regimen, with >96% efficacy being achieved from 21 days after the first treatment and thereafter until the end of the study (study duration: 90 days). In five of six studies incorporating three treatments at monthly intervals, the percentage reduction in R. sanguineus and D. variabilis counts 5 days after infestation ranged from 90 to 100% in the second and third months after treatment began. In the sixth study, reductions of > or =95% in D. variabilis counts 5 days after infestation were achieved for 2 weeks after each treatment in the second and third months. For the Monthly Plus regimen, from the second treatment (day 14) onwards, selamectin achieved 83-100% reductions in R. sanguineus and D. variabilis counts 3 days after infestation, and 94-100% reductions 5 days after infestation in three of the four studies. In the fourth study, selamectin demonstrated good efficacy against D. variabilis for 2 weeks after each treatment. In all seven studies, the counts from the selamectin-treated dogs were significantly (P< or =0.018) lower than those from the vehicle-treated dogs on 77 of the 80 assessments made 5 days after infestation. Selamectin also significantly (P< or =0.0105) reduced engorgement of female D. variabilis. These studies demonstrated that selamectin, administered topically to the skin in a single spot at a minimum dosage of 6mgkg(-1) at monthly intervals, was effective in the control of experimentally induced R. sanguineus and D. variabilis infestations on dogs.     

P‐24 Efficacy of selamectin in canine scabies and ear mite infestation in Korea

A randomized and controlled field study was performed in canine patients to evaluate the efficacy of selamectin in the treatment of naturally occurring Sarcoptes scabiei and Otodectes cynotis infestations in dogs. A total of 227 dogs from six veterinary practices in South Korea were included. Dogs were randomly assigned to treatment with selamectin or a positive‐control product. Selamectin was administered as a unit dose providing a minimum of 6 mg/kg in a topical preparation applied to the skin in a single spot on days 0 and 30 [S. scabiei (n = 113) and O. cynotis (n = 114)]. The presence of parasites was assessed before treatment and at 14, 30 and 60 days after the initiation of treatment. The animals were evaluated clinically at each assessment period. Based on skin scrapings, the efficacy of selamectin against S. scabiei infestations on dogs was >95% by day 30, and 100% by day 60. Against O. cynotis, selamectin eliminated mites in 100% of dogs by day 60. However, clinical signs of pruritus, erythema, scale, and crusted papules did not diminish concomittantly with resolution of S. scabiei in skin scrapings. The positive‐control products achieved similar results. Therefore, selamectin was safe and effective against sarcoptic mange and ear mites in dogs. Funding: Pfizer Animal Health.     

The efficacy of selamectin in the treatment of naturally acquired aural infestations of otodectes cynotis on dogs and cats

The efficacy of a novel avermectin, selamectin, was evaluated against naturally acquired aural infestations of Otodectes cynotis on dogs and cats. In four controlled and masked studies conducted in the USA and Europe, animals were allocated randomly to treatment with either selamectin at a minimum dosage of 6mgkg(-1) (range, 6-12. 5mgkg(-1)) or the vehicle only from the commercial formulation of selamectin (negative control). Treatments were administered topically in a single spot to the skin of each animal's back at the base of the neck in front of the scapulae. Cats were treated on day 0 only, and dogs were treated either on day 0 only or on days 0 and 30. The ears of dogs were examined otoscopically on day 14 for the presence of viable mites. Mite counts were conducted on day 30 for animals that had received one dose and on day 60 for animals that had received two doses. Percentage reductions in geometric mean mite counts for selamectin treatment compared with the vehicle were 100% for all animals on all count days. Analysis of variance, confirmed by Savage Scores, showed that ln(mite count+1) values were significantly (P< or =0.0015) lower for selamectin than for the vehicle for all animals on all count days. Thus, selamectin administered topically at a minimum dosage of 6mgkg(-1) was safe and 100% effective against naturally acquired aural infestations of O. cynotis in dogs and cats after a single dose or after two doses administered 1 month apart.     

An unusual presentation of canine distemper virus infection in a domestic ferret (Mustela putorius furo)

A 4.5-year-old, male castrated ferret was examined with a 27-day history of severe pruritus, generalized erythema and scaling. Skin scrapings and a trichogram were negative for mites and dermatophyte organisms. A fungal culture of hair samples was negative. The ferret was treated presumptively for scabies and secondary bacterial and yeast infection with selamectin, enrofloxacin, fluconazole, diphenhydramine and a miconazole–chlorhexidine shampoo. The ferret showed mild improvement in clinical signs over the subsequent 3 weeks, but was inappetent and required supportive feeding and subcutaneous fluids by the owner. The ferret was then examined on an emergency basis at the end of 3 weeks (53 days following initial signs of illness) for severe blood loss from a haematoma over the interscapular region, hypotension and shock. The owners elected euthanasia due to a poor prognosis and deteriorating condition. On post-mortem examination intraepithelial canine distemper viral inclusions were identified systemically, and abundant canine distemper virus antigen was identified with immunohistochemical staining. It is important to note the prolonged course of disease along with the absence of respiratory and neurological signs because this differs from the classic presentation of canine distemper virus infection in ferrets. Canine distemper virus should remain a clinical suspicion for ferrets with skin lesions that do not respond to appropriate therapy, even in animals that were previously vaccinated.     

Prevention of experimentally induced heartworm (Dirofilaria immitis) infections in dogs and cats with a single topical application of selamectin

In a series of six controlled studies (four in dogs, two in cats), heartworm-free dogs and cats were inoculated with Dirofilaria immitis larvae (L(3)) prior to topical treatment with the novel avermectin selamectin or a negative control containing inert formulation ingredients (vehicle). Selamectin and negative-control treatments were administered topically to the skin at the base of the neck in front of the scapulae. In dogs, selamectin was applied topically at dosages of 3 or 6mgkg(-1) at 30 days post-inoculation (PI), or of 3 or 6mgkg(-1) at 45 days PI, or of 6mgkg(-1) at 60 days PI. Cats were treated topically with unit doses providing a minimum dosage of 6mgkg(-1) selamectin at 30 days PI. Of the animals that were treated 30 days PI, some dogs were bathed with water or shampoo between 2 and 96h after treatment, and some cats were bathed with shampoo at 24h after treatment. Between 140 and 199 days PI, the animals were euthanized and examined for adult D. immitis. Adult heartworms developed in all control dogs (geometric mean count, 18.7 worms) and in 88% of control cats (geometric mean count, 2.1 worms). Selamectin was 100% effective in preventing heartworm development in dogs when administered as a single topical dose of 3 or 6mgkg(-1) at 30 days after infection, 3 or 6mgkg(-1) at 45 days after infection, or 6mgkg(-1) at 60 days after infection. Selamectin was 100% effective against heartworm infections in cats when administered as a single topical unit dose of 6mgkg(-1). Bathing with water or shampoo between 2 and 96h after treatment did not reduce the efficacy of selamectin as a heartworm prophylactic in dogs. Likewise, bathing with shampoo at 24h after treatment did not reduce the efficacy of selamectin in cats. These studies demonstrated that, at the recommended dosage and treatment interval, a single topical administration of selamectin was 100% effective in preventing the development of D. immitis in dogs and cats.     

Use of topical selamectin for the treatment of Trichosomoides crassicauda infection in laboratory rats

The present study investigated the efficacy of topical selamectin for elimination of naturally acquired Trichosomoides crassicauda infection in rats. Twelve T. crassicauda-positive rats were assigned to the treatment group and six rats were assigned to the control group. Selamectin (6 mg/kg) was applied topically to the skin in a single spot at the base of the neck in front of the scapulae in the treatment group. To assess the efficacy of the treatment, animal faeces were investigated with the use of the flotation technique on days 0, 4, 14 and 24 after selamectin application. The rats of the treatment and control groups were necropsied on the day 24. In the treatment group, 7 of 12 infected rats were cured completely. Topical selamectin was found to be effective in eliminating T. crassicauda infection in rats.     

Efficacy of selamectin in the treatment and control of clinical signs of flea allergy dermatitis in dogs and cats experimentally infested with fleas

OBJECTIVE: To determine whether treatment with selamectin would reduce clinical signs of flea allergy dermatitis (FAD) in dogs and cats housed in flea-infested environments. DESIGN: Randomized controlled trial. ANIMALS: 22 dogs and 17 cats confirmed to have FAD. PROCEDURE: Animals were housed in carpeted pens capable of supporting the flea life cycle and infested with 100 fleas (Ctenocephalides felis) on days -13 and -2 and on alternate weeks with 10 to 20 fleas. On day 0, 11 dogs and 8 cats were treated with selamectin (6 mg/kg [2.7 mg/lb]). Dogs were retreated on day 30; cats were retreated on days 30 and 60. All animals were examined periodically for clinical signs of FAD. Flea counts were conducted at weekly intervals. RESULTS: Throughout the study, geometric mean flea counts exceeded 100 for control animals and were < or = 11 for selamectin-treated animals. Selamectin-treated cats had significant improvements in the severity of miliary lesions and scaling or crusting on days 42 and 84, compared with conditions on day -8, and in severity of excoriation on day 42. In contrast, control cats did not have any significant improvements in any of the clinical signs of FAD. Selamectin-treated dogs had significant improvements in all clinical signs on days 28 and 61, but in control dogs, severity of clinical signs of FAD was not significantly different from baseline severity at any time. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that topical administration of selamectin, even without the use of supplementary environmental control measures and with minimal therapeutic intervention, can reduce the severity of clinical signs of FAD in dogs and cats.     

Brain penetration of ivermectin and selamectin in mdr1a,b P-glycoprotein- and bcrp- deficient knockout mice

P-glycoprotein, which is encoded by the multi-drug resistance gene (MDR1), highly restricts the entry of ivermectin into the brain by an ATP-driven efflux mechanism at the blood–brain barrier. In dogs with a homozygous MDR1 mutation though, ivermectin accumulates in the brain and provokes severe signs of neurotoxicosis and even death. In contrast to ivermectin, selamectin is safer in the treatment of MDR1 mutant dogs, suggesting that selamectin is transported differently by P-glycoprotein across the blood–brain barrier. To test this, we applied selamectin to mdr1-deficient mdr1a,b ^−/− knockout mice and wild-type mice. Brain penetration, organ distribution, and plasma kinetics were analyzed after intravenous, oral, and dermal spot-on application in comparison with ivermectin. We found that in vivo both macrocyclic lactone compounds are substrates of P-glycoprotein and that these strongly accumulate in the brain of mdr1a,b ^−/− knockout mice compared with wild-type mice at therapeutic doses of 12 mg/kg selamectin and 0.2 mg/kg ivermectin. However, selamectin accumulates to a much lesser degree (5–10 times) than ivermectin (36–60 times) in the absence of P-glycoprotein. This could explain the broader margin of safety of selamectin in MDR1 mutant dogs. In liver, kidney, and testes, ivermectin and selamectin accumulated less than four times as much in mdr1a,b mutant mice as in wild-type mice. Breast cancer resistance protein (Bcrp)-deficient bcrp ^−/− knockout mice were also included in the application studies, but showed no differences in brain concentrations or organ distribution of either ivermectin or selamectin compared with wild-type mice. This indicates that Bcrp is not a relevant efflux carrier for these macrocyclic lactone compounds in vivo at the blood–brain barrier.     

Safety of selamectin in dogs

Selamectin is a broad-spectrum avermectin endectocide for treatment and control of canine parasites. The objective of these studies was to evaluate the clinical safety of selamectin for topical use in dogs 6 weeks of age and older, including breeding animals, avermectin-sensitive Collies, and heartworm-positive animals. The margin of safety was evaluated in Beagles, which were 6 weeks old at study initiation. Reproductive, heartworm-positive, and oral safety studies were conducted in mature Beagles. Safety in Collies was evaluated in avermectin-sensitive, adult rough-coated Collies. Studies were designed to measure the safety of selamectin at the recommended dosage range of 6-12mgkg(-1) of body weight. Endpoints included clinical examinations, clinical pathology, gross and microscopic pathology, and reproductive indices. Selected variables in the margin of safety and reproductive safety studies were subjected to statistical analyses. Pups received large doses of selamectin at the beginning of the margin of safety study when they were 6 weeks of age and at their lowest body weight, yet displayed no clinical or pathologic evidence of toxicosis. Similarly, selamectin had no adverse effects on reproduction in adult male and female dogs. There were no adverse effects in avermectin-sensitive Collies or in heartworm-positive dogs. Oral administration of the topical formulation caused no adverse effects. Selamectin is safe for topical use on dogs at the recommended minimum dosage of 6mgkg(-1) (6-12mgkg(-1)) monthly starting at 6 weeks of age, and including dogs of reproducing age, avermectin-sensitive Collies, and heartworm-positive dogs.     

Pneumonyssoides species infestation in two Pekingese dogs in the UK

Two male, neutered, Pekingese dogs aged four years and 12 years were presented for acute-onset nasal pruritus and sneezing following a visit to a beach in northern Scotland. Routine nasal investigations revealed the presence of the canine nasal mite Pneumonyssoides both by direct visualisation and histopathologically. Resolution of clinical signs was observed following selamectin treatment. To the authors' knowledge, this report describes the first cases of Pneumonyssoides infestation in non-travelled UK dogs.     

Comparative speed of kill of selamectin, imidacloprid, and fipronil-(S)-methoprene spot-on formulations against fleas on cats

The speed of kill of selamectin, imidacloprid, and fipronil-(S)-methoprene against Ctenocephalides felis infestations on cats for one month following a single treatment was evaluated. Eighty cats were randomly allocated so that there were 20 cats in four different treatment groups. On Days -2, 7, 14, 21, and 28, each cat was infested with 100 adult C. felis from the Kansas 1 flea strain. Following initial application only imidacloprid had caused a significant reduction in adult fleas on treated cats within 6 hours, but by 24 hours all three formulations had killed 96.7% of the fleas. At 7 days post treatment, all three formulations reduced flea populations within 6 and 24 hours by 68.4% and 99.4%, respectively. At 21 and 28 days after treatment, none of the formulations killed significant numbers of fleas as compared to controls within 6 hours of infestation. At 28 days after treatment, selamectin, fipronil-(S)-methoprene, and imidacloprid had killed 99.0%, 86.4%, and 72.6% of the fleas within 48 hours of infestation, respectively. This study demonstrates that the speed of kill of residual flea products on cats decreases throughout the month following application. It also demonstrated that selamectin provided the highest level of residual activity on cats against the Kansas 1 flea strain.