T.L McTier

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 animals 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).

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 animals 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.

Evaluation of the effects of selamectin against adult and immature stages of fleas (Ctenocephalides felis felis) on dogs and cats

The adulticidal, ovicidal, and larvicidal effects of selamectin against flea (Ctenocephalides felis felis) infestations on dogs and cats were evaluated in a series of seven controlled and masked studies (three in cats, four in dogs). Animals were randomly allocated to treatment with either selamectin at a minimum dosage of 6mgkg(-1) in the commercial formulation or one of two negative-controls (0.9% NaCl solution or the vehicle from the commercial formulation). Treatments were administered topically in a single spot on the skin at the base of the neck in front of the scapulae. Speed of kill, measured by flea comb counts at 12h intervals during the 48h immediately following a single treatment on day 0, was evaluated in two studies. One study was in dogs and the other in cats, and each animal was infested with approximately 100 unfed viable adult fleas prior to treatment. Reductions in geometric mean flea counts for selamectin compared with saline were >98% between 24 and 36h after treatment in dogs, and between 12 and 24h after treatment in cats (P< or =0.0006). Efficacy in reducing flea egg hatch and larval development was evaluated in four studies, in which dogs and cats were treated once on day 0 and then repeatedly infested with approximately 600 fleas. Flea eggs were collected approximately for 72h after each infestation, on days 3, 7, 14, 21, and 30, counted, and cultured to determine their hatchability and subsequent larval development. Compared with the vehicle, selamectin was highly effective in reducing flea egg hatch (>92% in cats) and larval development (> or =95% for dogs and cats), and emergence of adults (97.8-100% for dogs, 85.6-100% for cats) for 30 days. Effects of exposure to hair coat debris were investigated in a study with dogs treated once on day 0 and repeatedly infested with 100 adult fleas. Debris (dander, flea faeces, hair, scales) was collected on days 1, 7, 14, 21, and 30 and added to normal flea eggs or larvae for incubation. Compared with debris from vehicle-treated dogs, debris from selamectin-treated dogs was highly effective in preventing egg hatch (>96%), in killing larvae (>98%) and in preventing larval development to adults (>99%) (P</=0.0033). Selamectin was shown to be highly effective in the treatment and control of flea infestations (C. felis) on dogs and cats. The adulticidal, ovicidal, and larvicidal effects of selamectin will be important in interrupting the flea life cycle by preventing the introduction and establishment of new flea infestations in a household environment.

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.

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 animals 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.

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).

Comparison of the activity of selamectin, fipronil, and imidacloprid against flea larvae (Ctenocephalides felis felis) in vitro.

The activity of selamectin, fipronil and imidacloprid against larval cat fleas (Ctenocephalides felis felis) was evaluated in an in vitro potency assay system. One hundred microliters of each compound at various concentrations in acetone were added to glass vials (1.5 by 3 cm) to which had been previously added 20 mg of sand and 10 mg of flea feces. Vials were then ball milled to allow the acetone to evaporate. Selamectin and fipronil were tested at 0.001, 0.003, 0.005, 0.01, 0.03, 0.05, 0.11, 0.3, and 0.5 microg of active compound per tube. Imidacloprid was tested at 0.01, 0.03, 0.05, 0.1, 0.3, 0.5, 1.0, 3.0, and 5.0 microg of active compound per tube. Thirty first instar C. felis larvae were added to each vial. The number of larvae remaining alive in each vial was determined once daily for 72 h. With selamectin, reductions of >/=93.5% were achieved at 24 h after exposure at doses of >/=0.3 microg. In contrast, at 24 h neither fipronil nor imidacloprid reached 90% reduction, even at the highest doses tested (0.5 microg for fipronil and 5.0 microg for imidacloprid). Selamectin was significantly (P</=0.05) more potent than imidacloprid and fipronil at levels >/=0.03 microg. A similar pattern of activity was observed at both 48 and 72 h, but higher percentages of larvae were killed for each of the compounds as the incubation time increased. At 72 h selamectin was significantly (P</=0.05) more potent than imidacloprid at levels of 0.01-0.1 microg and significantly (P</=0.05) more potent than fipronil at levels of 0.003-0.01 microg. Therefore, selamectin was more potent than either fipronil or imidacloprid in killing flea larvae in this in vitro assay system.

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.