Safety of selamectin in cats

The safety of the avermectin, selamectin, was evaluated for topical use on the skin of cats of age six weeks and above, including reproducing cats and cats infected with adult heartworms. All studies used healthy cats. Acute safety was evaluated in domestic cross-bred cats. Margin of safety was evaluated in domestic-shorthaired cats, starting at six weeks of age. Reproductive, heartworm-infected, and oral safety studies were conducted in adult, domestic-shorthaired cats. Studies were designed to measure the safety of selamectin at the recommended dosage range of 6-12mgkg(-1) of body weight. Assessments included clinical, biochemical, pathologic, and reproductive indices. Selected variables in the margin of safety study and the reproductive studies were subjected to statistical analyses by using a mixed linear model. Cats received large doses of selamectin at the beginning of the margin of safety study when they were six weeks of age and at their lowest body weight, yet displayed no clinical or pathologic evidence of toxicosis. Similarly, selamectin had no adverse effect on reproduction in adult male and female cats. There were no adverse effects in heartworm-infected cats. Oral administration of the topical formulation, which might occur accidentally, caused mild, intermittent, self-limiting salivation and vomiting. Selamectin is a broad-spectrum avermectin endectocide that is safe for use in cats starting at six weeks of age, including heartworm-infected cats and cats of reproducing age, when administered topically to the skin monthly at the recommended dosage to deliver at least 6mgkg(-1).     

Efficacy of selamectin against biting lice on dogs and cats

The efficacy of selamectin was evaluated against naturally acquired Trichodectes canis infestations on dogs and against Felicola subrostratus infestations on cats. Twenty dogs and 18 cats were randomly allocated to treatment with either a placebo or selamectin (6 mg/kg), administered topically once only on day 0. The treatment had no adverse effects in either the dogs or the cats. Efficacy was assessed by counting the live lice (adults and nymphs) on each animal by using a coat-parting technique on days -3, 7, 14, 21, 28, 35 and 42 for the dogs, and on days -1, 7, 21, 35 and 42 for the cats. On day 43, the number of live lice on each dog was also assessed by using a whole-body combing technique. Selamectin was 100 per cent effective in killing biting lice on the dogs and cats throughout the period of assessment; the louse counts on the treated dogs and cats were significantly lower than the pretreatment counts (P = 0.0001) and were also significantly lower than on the placebo-treated dogs (P < 0.05) and cats (P = 0.0001). There was a marked reduction in the prevalence of clinical signs associated with ectoparasite infestation in the treated dogs and no clinical signs were observed in any of the treated cats.     

Efficacy of selamectin in the treatment of nasal mite (Pneumonyssoides caninum) infection in dogs

In a laboratory study to evaluate the efficacy of selamectin for treatment of canine nasal mite infection, 12 purpose-bred beagles were experimentally infected with Pneumonyssoides caninum (P. caninum). Six of the dogs were treated with selamectin applied to the skin of the back at dosages of 6 to 24 mg/kg for three times at 2-week intervals. The remaining six dogs were an untreated control group. At necropsy 39 to 46 days after inoculation, no P. caninum mites were found in any of the treated dogs. In contrast, nasal mites were found in five of the untreated dogs. This difference was statistically significant at P=0.015.     

Pharmacokinetics of selamectin following intravenous,oral and topical administration in cats and dogs

The pharmacokinetics of selamectin were evaluated in cats and dogs, following intravenous (0.05, 0.1 and 0.2 mg/kg), topical (24 mg/kg) and oral (24 mg/kg) administration. Following selamectin administration, serial blood samples were collected and plasma concentrations were determined by high performance liquid chromatography (HPLC). After intravenous administration of selamectin to cats and dogs, the mean maximum plasma concentrations and area under the concentration-time curve (AUC) were linearly related to the dose, and mean systemic clearance (Clb) and steady-state volume of distribution (Vd(ss)) were independent of dose. Plasma concentrations after intravenous administration declined polyexponentially in cats and biphasically in dogs, with mean terminal phase half-lives (t(1/2)) of approximately 69 h in cats and 14 h in dogs. In cats, overall Clb was 0.470 +/- 0.039 mL/min/kg (+/-SD) and overall Vd(ss) was 2.19 +/- 0.05 L/kg, compared with values of 1.18 +/- 0.31 mL/min/kg and 1.24 +/- 0.26 L/kg, respectively, in dogs. After topical administration, the mean C(max) in cats was 5513 +/- 2173 ng/mL reached at a time (T(max)) of 15 +/- 12 h postadministration; in dogs, C(max) was 86.5 +/- 34.0 ng/mL at T(max) of 72 +/- 48 h. Bioavailability was 74% in cats and 4.4% in dogs. Following oral administration to cats, mean C(max) was 11,929 +/- 5922 ng/mL at T(max) of 7 +/- 6 h and bioavailability was 109%. In dogs, mean C(max) was 7630 +/- 3140 ng/mL at T(max) of 8 +/- 5 h and bioavailability was 62%. There were no selamectin-related adverse effects and no sex differences in pharmacokinetic parameters. Linearity was established in cats and dogs for plasma concentrations up to 874 and 636 ng/mL, respectively. Pharmacokinetic evaluations for selamectin following intravenous administration indicated a slower elimination from the central compartment in cats than in dogs. This was reflected in slower clearance and longer t(1/2) in cats, probably as a result of species-related differences in metabolism and excretion. Inter-species differences in pharmacokinetic profiles were also observed following topical administration where differences in transdermal flux rates may have contributed to the overall differences in systemic bioavailability.     

Evaluation of efficacy of selamectin, fipronil, and imidacloprid against Ctenocephalides felis in dogs

OBJECTIVE: To evaluate efficacy of monthly administration of selamectin, fipronil, and imidacloprid against Ctenocephalides felis in dogs. DESIGN: Randomized controlled trial. ANIMALS: 44 healthy dogs. PROCEDURE: Dogs known to be free of fleas were infested with 100 unfed adult fleas on days -28 and -21. On days 0, 30, 60, 90, and 120, dogs (12/group) were treated by topical administration of selamectin (6 mg/kg [2.7 mg/lb] of body weight), fipronil (7.5 mg/kg [3.4 mg/lb]), or imidacloprid (10 mg/kg [4.5 mg/lb]); 8 untreated dogs were used as controls. On day -6 and every 2 weeks after initial treatment, comb counts of viable adult fleas were made, and fleas (< or =50/dog) were replaced onto the dog from which they were removed. On day 89, fleas were not replaced. On day 91 and every 7 days until the end of the study, dogs were challenged with 20 adult fleas. RESULTS: 14 days after initial treatment, geometric mean flea counts were reduced by 97.5 to 99.1 % for all treatments, compared with pretreatment counts on day -6. Selamectin, fipronil, and imidacloprid reduced geometric mean flea counts by 99.7 to 100% from day 29 to the end of the study. CONCLUSIONS AND CLINICAL RELEVANCE: Selamectin is as effective as fipronil and imidacloprid in reducing C felis infestation in dogs housed for 3 months in a flea-infested environment under conditions known to support the flea life cycle, and in protecting against subsequent weekly challenges with C felis for an additional 2 months.     

The efficacy of selamectin in the treatment of naturally acquired infestations of sarcoptes scabiei on dogs

Selamectin, a novel avermectin, was evaluated for its effect on naturally occurring infestations of Sarcoptes scabiei in 42 dogs. In two controlled and masked laboratory studies conducted in the USA and Italy, infested dogs received treatment with either selamectin (6mgkg(-1); range: 6-12mgkg(-1)) or the vehicle only (negative control). Treatments were administered topically to the skin on each animal's back at the base of the neck in front of the scapulae. Study day 0 was defined as the first day of treatment administration. Dogs were treated on days 0 and 30, and efficacy was assessed by counting viable mites recovered from skin scrapings performed on each dog on days 14, 29 or 30, 44, and 60, and by categorising the clinical signs of canine scabies on the same days. Percentage reductions in geometric mean mite counts for selamectin, compared with vehicle, on days 14, 29 or 30, 44, and 60 were > or =98.1, > or =93.5, 100, and 100%, respectively. Analysis of variance, confirmed by Savage Scores, showed that ln(mite counts+1) values for selamectin-treated dogs were significantly lower (P< or =0.0391) than those for vehicle-treated dogs on all post-treatment assessment days. Clinical signs of scabies were markedly reduced in selamectin-treated dogs, compared with vehicle-treated dogs. Topical administration to the skin in a single spot of a single unit dose of selamectin, or of two unit doses given 1 month apart, each providing at least the recommended minimum dosage of 6mgkg(-1), was highly effective against naturally acquired infestations of S. scabiei in dogs, reducing mite counts by >93% (single dose) and 100% (two doses).     

Preliminary findings on the efficacy of selamectin in the treatment of dogs naturally infected with Dirofilaria repens

Subcutaneous dirofilariosis caused by Dirofilaria repens is common in dogs and it is an emerging helminthozoonosis in Europe, Asia, Africa and also in Hungary. Macrocyclic lactones are used for preventing the infection; however, their activity against the microfilariae and mature stages of this species is questionable. Selamectin is widely used for the prophylaxis of heartworm (D. immitis) infection. The objective of the present study was to test the microfilaricidal efficacy of the topical formulation of selamectin in dogs naturally infected with D. repens . A total of 78 Beagle dogs were examined for the presence of circulating microfilariae by Knott's test. Twenty-three of the microfilaraemic dogs were divided into four groups and included in the trial. The dogs received monthly or biweekly selamectin treatment and were subjected to monthly blood testing for a period of 252 or 336 days. At the end of the study, 65% of the dogs were not microfilaraemic and the rest had low number of microfilariae in their blood. These results indicate that chronic spot-on selamectin treatment may be a useful tool also in the control of canine subcutaneous dirofilariosis.     

Efficacy and safety of selamectin against fleas on dogs and cats presented as veterinary patients in Europe

Two controlled and masked multi-centre studies were conducted to examine the efficacy of a novel topical avermectin, selamectin, against natural flea infestations on 418 dogs and 345 cats. Veterinary patients with viable flea infestations were enrolled in the studies, which were conducted in United Kingdom, France, Germany, and Italy. Animals were allocated randomly in a 2:1 ratio to one of two treatments: either selamectin alone at a minimum dosage of 6mgkg(-1) or fenthion at recommended dose rates. Concurrent use of an environmental spray (containing methoprene and either pyrethrins or permethrin) was permitted only for fenthion-treated animals. In-contact cats and dogs (animals living in the same home) received the same treatment as the first animal enrolled from the household, if recommended by the veterinarian. Study day 0 was defined as the day of first treatment. Animals were treated on days 0, 30, and 60, and flea comb counts and clinical evaluations were conducted on days 0, 14, 30, 60, and 90. Analysis of variance of ln(flea count+1) showed that values were significantly lower for selamectin alone compared with fenthion (with or without the concurrent use of an environmental spray) in dogs on days 30, 60, and 90 (P<0.05) and in cats on days 14, 30, 60, and 90 (P<0.01). For selamectin, the reductions in geometric mean flea counts on days 14, 30, 60, and 90, compared with day 0, were 92.5, 90.7, 98.1, and 99.1%, respectively, for dogs and 92.8, 92.7, 97.7, and 98.4%, respectively, for cats. Selamectin was shown to be safe and highly effective in the control of naturally acquired flea infestations on dogs and cats presented as veterinary patients in Europe.     

Efficacy and safety of selamectin against Sarcoptes scabiei on dogs and Otodectes cynotis on dogs and cats presented as veterinary patients

A series of randomized, controlled and masked field studies was conducted in veterinary patients to evaluate the efficacy of selamectin, a novel avermectin, in the treatment of naturally occurring Sarcoptes scabiei infestations on dogs and Otodectes cynotis infestations on dogs and cats. A total of 342 dogs and 237 cats participated in these studies, which were conducted at 40 veterinary practices in the USA and Europe. Animals were randomly assigned to treatment with selamectin or a positive-control product (existing approved products). Selamectin was administered as a unit dose providing a minimum of 6mgkg(-1) (range: 6-12mgkg(-1)) in a topical preparation applied to the skin in a single spot on day 0 (O. cynotis in cats, n=144), or on days 0 and 30 (O. cynotis and S. scabiei in dogs, n=83 and n=122, respectively). The presence of parasites was assessed before treatment and at 30 days (for all studies) and 60 days (for O. cynotis and S. scabiei dog studies) after first treatment. The animals were also 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 94-100% of cats by day 30, and in 90% of dogs by day 60. The positive-control products achieved similar results. Thus, selamectin was safe and effective against ear mites in dogs and cats and sarcoptic mange in dogs when used in field (veterinary patient) studies in dogs and cats of a wide variety of ages and breeds.     

Efficacy of selamectin in the prevention of adult heartworm (Dirofilaria immitis) infection in dogs in northern Italy

The efficacy of a novel avermectin, selamectin, was evaluated for the prevention of heartworm disease (adult Dirofilaria immitis infection) in 120 dogs (aged 9 months to 13 years at enrolment) presented as veterinary patients. The study was conducted at five veterinary practices in a heartworm hyperendemic region of northern Italy. Dogs were allocated randomly in a 2:1 ratio to treatment with either selamectin or ivermectin. Treatments were administered at monthly intervals for 6 months during the heartworm transmission season (May-November). Selamectin was applied topically in a single spot to the skin on each animal's back at the base of the neck in front of the scapulae as a unit dose that provided at least the minimum recommended dosage of 6mgkg(-1) (range, 6-12mgkg(-1)). Ivermectin (6microgkg(-1) of body weight) was administered orally at monthly intervals, in accordance with the manufacturer's product label recommendations. Study day 0 was defined individually for each dog as the day of first treatment administration. Efficacy was assessed on the basis of the absence of D. immitis microfilariae and adult heartworm (D. immitis) antigen in tests conducted on days 180 and 300. There were no adverse clinical signs arising due to treatment with selamectin and no drug-related mortalities. The prevention rate for D. immitis microfilariae and adult heartworm antigen was 100% for both selamectin and ivermectin. Thus, selamectin administered as a unit dose, providing at least the recommended minimum dosage of 6mgkg(-1), at monthly intervals during the heartworm transmission season was safe and 100% effective in the prevention of heartworm disease in dogs presented as veterinary patients.     

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.     

Clinical efficacy of selamectin in the treatment of naturally acquired infection of sucking lice (Linognathus setosus) in dogs

A clinical study was performed in 21 dogs to evaluate the efficacy of selamectin for the treatment of naturally acquired infection of sucking lice (Linognathus setosus [L.setosus]) in dogs. Each dog was randomly assigned to one of two treatment groups. One group was treated with selamectin applied topically at a mean dosage of 7.9 mg/kg. The other group was treated with permethrin applied topically at a mean dosage of 85.7 mg/kg. At day 42 posttreatment, all animals remaining in the study (10 treated with selamectin and six with permethrin) were clear of lice. In both groups, the reduction in lice counts from pretreatment values to day 42 was statistically significant at P< or =0.0001. Selamectin applied topically appeared to be effective against L. setosus infection in dogs.     

Repellency and efficacy of 65% permethrin and selamectin spot-on formulations against Ixodes ricinus ticks on dogs

Two topically applied spot-on products used for flea and tick control on dogs, 65% permethrin (Defend EXspot Treatment for Dogs, Schering-Plough Animal Health Corp., Union, NJ) and selamectin (Revolution [United States] or Stronghold [Europe], Pfizer Animal Health, New York, NY), were evaluated for repellency and efficacy against Ixodes ricinus, the primary vector of Lyme disease in Europe. Eighteen dogs were evenly and randomly allocated to the following treatments: 1) 65% permethrin, 2) selamectin, 3) untreated control. Dogs were treated by topical application of the assigned product in accordance with product label directions on Day 0. At 7, 14, 21, 28, and 35 days after treatment, each dog was exposed for 2 hours to 50 unfed, adult ticks in a cage with a carpet that covered approximately 70% of the floor area. After the exposure period, dogs were removed from the cages and live and dead ticks were counted on the dogs and in the cages. The number of live ticks recovered was reduced by 90.3% to 99.5% for dogs treated with 65% permethrin (P <.0001 versus controls and selamectin), compared with 10.9% to 31.1% for dogs treated with selamectin (P >.05 versus controls). The repellency of 65% permethrin was 63.4% to 80.2% against I. ricinus ticks (P <.0001 versus controls, P <.0007 versus selamectin), compared with 0% to 10.9% repellency for selamectin (P >.05 versus controls).     

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.     

Efficacy and safety of selamectin against fleas and heartworms in dogs and cats presented as veterinary patients in North America

A series of randomized, controlled, masked field studies was conducted to assess the efficacy and safety of selamectin in the treatment of flea infestations on dogs and cats, and in the prevention of heartworm infection in dogs. In addition, observations were made on the beneficial effect of selamectin treatment on dogs and cats showing signs of flea allergy dermatitis (FAD). In all studies selamectin was applied topically, once per month, in unit doses providing a minimum dosage of 6mgkg(-1). Dogs and cats with naturally occurring flea infestations, some of which also had signs associated with FAD, were assigned randomly to receive three months of topical treatment with selamectin (220 dogs, 189 cats) or a positive-control product (dogs: fenthion, n=81; cats: pyrethrins, n=66). Selamectin was administered on days 0, 30, and 60. Day 0 was defined as the day that the animal first received treatment. Flea burdens were assessed by flea comb counts and clinical evaluations of FAD were performed before treatment, and on days 14, 30, 60, and 90. On days 30, 60, and 90, mean flea counts in selamectin-treated dogs were reduced by 92.1, 99.0, and 99.8%, and mean flea counts in fenthion-treated dogs were reduced by 81.5, 86.8, and 86.1%, respectively, compared with day 0 counts. Also, on days 30, 60, and 90, mean flea counts in selamectin-treated cats were reduced by 92.5, 98.3, and 99.3%, and mean flea counts in pyrethrin-treated cats were reduced by 66.4, 73.9, and 81.3%, respectively, compared with day 0 counts. Selamectin also was beneficial in alleviating signs in dogs and cats diagnosed clinically with FAD. A total of 397 dogs free of adult heartworm infection from four heartworm-endemic areas of the USA were allocated randomly to six months of treatment with selamectin (n=298) or ivermectin (n=99). Selamectin achieved a heartworm prevention rate of 100%, with all dogs testing negative for microfilariae and adult heartworm antigen on days 180 and 300. Selamectin was administered to a total of 673 dogs and 347 cats having an age range of 6 weeks to 19 years (3954 doses). The animals included 19 purebred or crossbred Collies (Bearded, Border, and unspecified). There were no serious adverse events. Results of these studies indicated that selamectin was highly effective in the control of flea infestations in dogs and cats without the need for simultaneous treatment of the environment or of in-contact animals and also was beneficial in alleviating signs associated with FAD. Selamectin also was 100% effective in preventing the development of canine heartworms and was safe for topical use in dogs and 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.     

Dose selection of selamectin for efficacy against adult fleas (Ctenocephalides felis felis) on dogs and cats

Selamectin, a novel avermectin, was evaluated in two controlled studies (one in Beagles, one in domestic shorthaired cats) to determine an appropriate topical dose for efficacy against adult Ctenocephalides felis felis (C. felis) fleas on dogs and cats for 1 month. For each study, animals were allocated randomly to four treatments. One treatment consisted of the inert formulation ingredients (vehicle) administered as a negative control, and the other three treatments consisted of a single topical dosage of 3, 6, or 9mgkg(-1) of selamectin. In each study, selamectin was administered as a topical dose applied to the skin in a single spot at the base of the neck in front of the scapulae. Dogs and cats were infested with 100 viable unfed C. felis (50 males and 50 females) on days 4, 11, 18, and 27. Seventy-two hours (+/-2h) after each infestation, on days 7, 14, 21, and 30, a comb count to determine the number of viable fleas present on each animal was performed. Efficacy of selamectin on day 30 was used to select an appropriate dose. For dogs and cats, percentage reductions in geometric mean flea comb counts for the three selamectin treatments ranged from 94. 6 to 100% on days 7, 14, and 21, compared with the negative-control treatment. On day 30, reductions in flea comb counts were 81.5, 94.7, and 90.8% for dogs, and 79.8, 98.0, and 96.2% for cats treated with selamectin at 3, 6, or 9mgkg(-1), respectively. For day 30 flea comb counts for dogs and cats, analysis of variance showed that the three selamectin treatments resulted in significantly (P< or =0.05) lower counts than did the negative-control treatment. For dogs and cats, geometric mean flea counts for selamectin administered at a dosage of 3mgkg(-1) were significantly (P< or =0.05) higher than those for the 6 and 9mgkg(-1) treatment dosages combined. There were no significant differences in flea counts between the 6 and 9mgkg(-1) treatments. This analysis was confirmed by linear-plateau modeling. Thus, the optimal dose of selamectin for efficacy against adult fleas for both dogs and cats, as estimated by the turning point (plateau) in the dose response curve, was 6mgkg(-1).     

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.     

Efficacy of selamectin against adult flea infestations (Ctenocephalides felis felis and Ctenocephalides canis) on dogs and cats

Selamectin was evaluated in eight controlled studies (4 in dogs, 4 in cats) to determine the efficacy of a single topical unit dose providing the recommended minimum dosage of 6mgkg(-1) against Ctenocephalides felis felis and Ctenocephalides canis fleas on dogs and against C. felis on cats. In addition, the effect of bathing on the efficacy of selamectin against C. felis was evaluated. Identical studies were performed in Beagles and domestic shorthaired cats. For each study, animals were allocated randomly to treatments of 8-12 animals each. All studies (dog studies A, B, C, and D and cat studies A, B, C, and D) evaluated the efficacy of selamectin without bathing. In addition, study C in both dogs and cats evaluated efficacy with a shampoo bath at 24h after dosing, and study D evaluated the efficacy of selamectin with water soaking at 2h after dosing or with a shampoo bath at 2-6h after dosing. Dog study B evaluated efficacy against C. canis, whereas all other studies used C. felis. In each study, selamectin was administered on day 0 as a topical dose that was applied directly to the skin in a single spot at the base of the neck in front of the scapulae. Dogs and cats were infested with approximately 100 viable unfed C. felis or C. canis on days 4, 11, 18, and 27. On days 7, 14, 21, and 30, approximately 72h after infestation, a comb count of the number of viable fleas present on each animal was made. For C. felis and C. canis for dogs and cats, compared with controls, selamectin achieved significant reductions in geometric mean adult flea comb counts of > or =98.9% on days 7, 14, and 21 in all eight studies. On day 30, the reduction for C. felis remained at or above 98.0%. This included the dogs and cats that were soaked with water or bathed with shampoo at 2, 6, or 24h after treatment. There were no significant (P>0.05) differences between the flea counts from selamectin-treated animals in these studies, regardless of bathing status. On day 30, a significant reduction of 91.8% was achieved against C. canis on dogs. Thus, these studies demonstrated that a single topical unit dose of selamectin was highly effective against adult fleas on dogs and cats for at least 27 days.