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.     

Comparison of the activity of selamectin, imidacloprid and fipronil for the treatment of cats infested experimentally with Ctenocephalides felis felis and Ctenocephalides felis strongylus

Twenty adult, domestic short hair cats were randomly allocated into four groups of five cats and housed in separated cages. Each cat was infested with 25 fleas Ctenocephalides felis felis and 25 Ctenocephalides felis strongylus and 2 days later (day 0) the cats in group 1, 2 and 3 received a spot on application of selamectin, imidacloprid or fipronil, respectively, while the cats in group four were not treated. The cats were combed 48 h later, the fleas were removed, counted and their subspecies were determined. All the cats were reinfested with the same number of the two subspecies of fleas on days 7, 14, 21, 29 and 35. The efficacy of each treatment was calculated 48 h after each infestation. The mean number of fleas on the control cats was 16.4 C. f. felis and 13.4 C. f. strongylus. The three treatments were effective for the first 31 days for C. f. felis and for the full 37 days for C. f. strongylus. Over the first 31 days, the efficacy of selamectin ranged from 89 to 100% and 85 to 100% against C. f. felis and C. f. strongylus, respectively, the efficacy of imidacloprid ranged from 76 to 100% and 92 to 100% and the efficacy of fipronil ranged from 98 to 100% and 97 to 100% against C. f. felis and C. f. strongylus. There were no significant differences between the control of C. f. felis and C. f. strongylus by the three products.     

Evaluation of efficacy of selamectin and fipronil against Ctenocephalides felis in cats

OBJECTIVE: To evaluate efficacy of monthly administration of selamectin and fipronil against Ctenocephalides felis in cats. DESIGN: Randomized controlled trial. ANIMALS: 36 healthy cats. PROCEDURE: Cats 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, sixteen cats (8 pairs/treatment group) were treated by topical administration of selamectin (6 mg/kg [2.7 mg/lb] of body weight) or fipronil (7.5 mg/kg [3.4 mg/lb]). Four control cats (2 pairs) were not treated. On day -6 and every 2 weeks after initial treatment, comb counts were performed to detect fleas. Flea counts were recorded, and fleas (< or =50) that had been removed were replaced onto the cat. On day 89, fleas were not replaced. On day 91 and every 7 days until the end of the study (day 150), cats were challenged with 20 adult fleas. Flea counts were compared between and within treatments. RESULTS: 14 days after treatment, geometric mean flea counts were reduced by 71.2% by fipronil treatment and 35.3% by selamectin treatment. Both treatments resulted in 97 to 98% reduction in flea counts on day 29 and 99.8 to 100% reduction from day 44 to the end of the study. CONCLUSIONS AND CLINICAL Relevance: Selamectin is as effective as fipronil in treating infestation in cats 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.     

Control of fleas on naturally infested dogs and cats and in private residences with topical spot applications of fipronil or imidacloprid

Thirty-four flea-infested dogs and cats residing in 20 homes in Tampa, FL were randomly placed into 1 of 2 treatment groups during the summer of 1997. Pets were treated topically with either 10.0%w/v imidacloprid or 10%w/v fipronil spot-on on day 0, then once for every 28-30 days for 90 days. Flea populations were assessed in the environment using an intermittent-light trap, while pet flea burdens were assessed using visual area counts. A single application of imidacloprid was 95.3 and 97.4% effective in reducing flea populations on pets at 7 and 28 days, respectively. A single application of fipronil was 97.5 and 97.0% effective in reducing flea populations on pets at the same time points. Following 3 monthly applications of either imidacloprid or fipronil, flea burdens on pets were reduced by 99.5 and 96.5%, respectively. In addition, flea numbers in the in-home environment were reduced by 99. 0 and 98.6% in homes, where pets were treated with imidacloprid or fipronil, respectively.     

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/=0.03 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相似文献   

Effect of topical application of fipronil in cats with flea allergic dermatitis

OBJECTIVE: To determine whether topical application of a 10% fipronil solution would control signs of flea allergic dermatitis in cats housed under natural conditions. DESIGN: Multicenter open clinical trial. ANIMALS: 42 client-owned cats with flea allergic dermatitis. PROCEDURES: Study cats along with all other cats and dogs living in the same houses were treated with 10% fipronil solution topically on days 0, 30, and 60. Flea counts and clinical assessments were performed on study cats on days 0, 14, 30, 60, and 90. RESULTS: Percentage reductions in geometric mean flea counts on days 14, 30, 60, and 90, compared with day-0 geometric mean count, were 75, 73, 85, and 94%, respectively. Pruritus score was significantly improved at each examination after day 0, and pruritus was reduced or eliminated in 31 of 40 (78%) cats at the final examination. Similarly, scores for severity of miliary dermatitis and alopecia were significantly improved at each examination, except for alopecia score on day 14. Overall treatment efficacy, assessed on day 90, was excellent for 28 (70%) cats, good for 6 (15%), moderate for 3 (7.5%), and poor for 3 (7.5%). CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that monthly topical application of fipronil is effective for treatment of flea allergic dermatitis in cats housed under natural conditions.     

Comparison of the activity of selamectin, imidacloprid and fipronil for the treatment of dogs infested experimentally with Ctenocephalides canis and Ctenocephalides felis felis.

Twenty-four beagles were randomly allocated into four groups of six and housed in separate cages. Each dog was infested with 25 Ctenocephalides canis and 25 Ctenocephalides felis felis and two days later (day 0) the dogs in groups 1, 2 and 3 received a spot-on application of selamectin (6 mg/kg), imidacloprid (10 mg/kg), or fipronil (6-7 mg/kg), respectively, while the dogs in group 4 were not treated. The dogs were combed 48 hours later, the fleas were removed, counted and their species were determined. All the dogs were reinfested with the same number of the two species of fleas on days 7, 14, 21, 28 and 35, and the efficacy of the treatments was calculated 48 hours after each infestation. The mean numbers of fleas on the control dogs were 19.8 C. canis and 14.7 C. felis felis. The three treatments were effective for the full 35 days of the trial; over the first 28 days, the efficacy of selamectin ranged from 81 to 100 and 92 to 99 per cent against C. felis felis and C canis, respectively, the efficacy of imidacloprid ranged from 98 to 100 per cent and the efficacy of fipronil was 100 per cent against both species. There were no significant differences between the three treatments.     

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.     

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.     

Toxicity in three dogs from accidental oral administration of a topical endectocide containing moxidectin and imidacloprid

Three dogs were presented with a history of oral administration of a topical endectocide containing imidacloprid and moxidectin. They were diagnosed with imidacloprid and moxidectin intoxication, having ingested doses ranging from 7.5 to 1.4 mg/kg of imidacloprid and 1.9 to 2.8 mg/kg of moxidectin. The three dogs were affected to different degrees of severity, but all displayed signs of ataxia, generalised muscle tremors, paresis, hypersalivation and disorientation. Temporary blindness occurred in two cases. The three dogs were tested for the presence of the multi-drug resistance 1 gene deletion, which can cause an increased sensitivity to the toxic effects of moxidectin, and were found to be negative. Treatment included gastrointestinal decontamination, intravenous fluid therapy and benzodiazepines to control muscle tremors. All three dogs made a complete recovery within 48 h of ingestion.     

Dermal safety study with imidacloprid/moxidectin topical solution in the ivermectin-sensitive collie

A study was conducted to determine the safety of the dermal application of 10% imidacloprid/2.5% moxidectin topical solution in ivermectin-sensitive collies. Each milliliter of this solution contains 100mg of imidacloprid and 25mg of moxidectin. A total of 21 collies were prescreened for ivermectin-sensitivity and heartworm negative status prior to selection for the study. Animals were assigned based on the maximum ivermectin-sensitivity score demonstrated during the prestudy screening. Treatment groups included a 3x and 5x test article group, and a 3x and 5x mineral oil control group. The 3x and 5x doses were administered at three and five times, respectively, the 1x dose based on the animal's body weight. On day 0, 3 of the 21 dogs were treated with dermal applications of a preliminary dose of 3x test article to screen for unexpected signs of toxicity with the remaining 18 dogs being treated with 3x mineral oil to blind for the volume of liquid applied. After no signs of toxicity were observed, these same three dogs were treated with 3x of test article and 2x mineral oil on days 28 and 56. The remaining 18 animals were equally allocated to either a 5x test article group or a 5x control group and were each treated on days 28, 56, and 84. Personnel performing observations were blinded to treatment. Observations were made for clinical signs of ivermectin sensitivity twice daily during non-dosing days. On treatment days, dogs were observed hourly for the first 4h post-treatment and at 6, 8, 12, 18 and 24h. Signs of toxicosis were not observed in any of the dogs throughout the observation period. This study demonstrated the safety of imidacloprid/moxidectin, when administered to collies testing positive for ivermectin sensitivity at dosages up to five times the maximum recommended dose.     

Relationships between electromyographic ileal and colonic motility patterns in cats during fasting and feeding.

The relationship between ileal and colonic electromyographic motility patterns were investigated in six awake cats chronically fitted with subserosal electrodes implanted in the smooth muscles of the ileum and colon. Smooth muscle electrical activity (electromyogram) was recorded in both fed and fasted conditions under a 12-12 hours dark-light schedule. It consisted of electrical long spike bursts having two different patterns for each condition. Short sequences of three to five long spike bursts were propagated either aborally or orally from any part of the colon; they were most frequent during the interdigestive or fasting period and no relationship was observed between these long spike bursts and the electrical activity of the ileum. During the digestive or feeding period, the colonic activity was organized in long sequences of 10-15 long spike bursts, termed migrating spike bursts, which started near the caecal junction and propagated aborally to the distal colon. These migrating spike bursts were correlated with the ileal motility. This relationship demonstrated between ileum and colon after feeding is dependent upon the amount of food intake.     

Assessment of owner-administered monthly treatments with oral spinosad or topical spot-on fipronil/(S)-methoprene in controlling fleas and associated pruritus in dogs

Monitoring of the performance of flea control products under conditions of natural challenge is valuable in assessing continued effectiveness and determining the ongoing relevance of laboratory studies. A multi-clinic, investigator-blinded study was undertaken in client-owned dogs to investigate and compare the flea control provided by 3 consecutive monthly treatments of oral spinosad (SPN) or fipronil/(S)-methoprene topical (FSM) spot-on. The first household dog meeting enrollment criteria and with at least 10 fleas (whole-body flea count) served as the index dog in a household against which primary objectives were set. Stratification was based on pruritus scores at the enrollment visit and on single or multiple pet household. Index pets were randomized to treatment with either SPN or FSM, dispensed on day 0 for at-home administration by owners. All other household dogs and cats, maximum 4 pets per household, were dispensed the same treatment as the index dog (spinetoram was dispensed for cats in SPN households). Subsequent treatments were dispensed when index dogs were returned for whole-body flea counts and pruritus-scoring at visits on days 30 and 60, with final assessments on day 90 (±5 days on each occasion). Primary endpoints were the number of flea-free index dogs in each group one month after the final treatment, the reduction in owner-reported pruritus, and the reduction from baseline mean flea counts. One hundred twenty eight index dogs were enrolled (65 in the SPN arm; 63 in the FSM arm) at 10 clinics in FL (6), NC (2), LA (1), and TX (1). On day 0, geometric mean flea counts were 57.7 (range: 10–1469) and 44.8 (10–717) for the SPN and FSM groups, respectively. On Day 90, 55 of 58 (95%) and 21 of 55 (38%) index dogs completing the study were flea-free in SPN and FSM groups, respectively; mean SPN pruritus scores declined to 0.92 (6.67 on day 0), and to 3.83 (6.33 on day 0) for FSM; geometric mean flea counts (% control) were 0.08 (99.9%) and 5.19 (88.4%), for SPN and FSM groups, respectively. Between-treatment differences were highly statistically significant (p < 0.0001). In conclusion, SPN provided reliable flea control in client-owned dogs, regardless of challenge level.     

Application of an electrometric method for measurement of blood cholinesterase activities in sheep, goats and cattle treated with organophosphate insecticides

A modified electrometric cholinesterase method has been described for use in ruminants exposed to organophosphate insecticides. The method was used to measure cholinesterase activities in the plasma and erythrocytes of sheep, goats and cattle treated with organophosphate insecticides under field conditions. The animals were treated topically to control ectoparasites with malathion (0.05%) or diazinon (0.06%). The treated animals did not suffer from adverse effects related to cholinesterase inhibition. However, 2 h after treatments, plasma and erythrocyte cholinesterase activities significantly decreased in sheep by 20% and 39% and in goats by 18% and 30%, respectively, when compared with respective untreated control values. Diazinon did not significantly affect plasma and erythrocyte cholinesterase activities in the cattle. The results suggest that the described electrometric method could be efficiently used for detecting cholinesterase inhibition in ruminants exposed to organophosphate insecticides.     

Chrysomya bezziana (Diptera: Calliphoridae) infestation in two Malaysian cats treated with oral lotilaner

The most common fly species associated with screwworm myiasis in Southeast Asia is Chrysomya bezziana (Ch. bezziana), the Old‐World screwworm. Treatment of screwworm myiasis in cats traditionally has comprised subcutaneous injection of ivermectin or oral administration of nitenpyram, combined with aggressive tissue debridement and larval removal under general anaesthesia. Two cats diagnosed with cutaneous myiasis caused by the larvae of Ch. bezziana were treated with lotilaner. In both cats, a single dose of lotilaner at 6–26 mg/kg, killed all larvae within 24 h, negating the need for general anaesthesia. Both cats were simultaneously infested with Lynxacarus radovskyi (L. radovskyi) which also was eradicated with lotilaner. No adverse reactions were observed and both cats recovered without complications.     

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.     

Clinical, clinicopathological and histological changes observed in 14 cats treated with glucocorticoids

Fourteen cats were given immunosuppressive doses of either prednisolone (4.4 mg/kg/day) or dexamethasone (0.55 mg/kg/day) for 56 days. Complete blood counts, serum biochemistry profiles and urinalyses were performed on days 0 and 56, and liver biopsies were taken laparoscopically on day 56, because of evidence of hepatic disease on the serum biochemistry profiles. There were significant increases in the cats' mean white blood cell counts, neutrophil counts and monocyte counts, and significant decreases in their mean lymphocyte counts and eosinophil counts. There were consistent increases in the serum concentrations of albumin, glucose, triglycerides and cholesterol. Glycogen deposition, consistent with a steroid hepatopathy, was present to varying degrees in all the liver biopsies. One of the cats developed adverse clinical signs including anorexia, icterus, pruritus and medial curling of the pinnae, some of which were suspected to be related to the glucocorticoid therapy.