metaflumizone and Ectoparasitic-Infestations

A spot-on metaflumizone formulation was evaluated to determine its adulticidal efficacy, effect upon egg production, and ovicidal activity when applied to flea infested cats. Eight male and eight female adult domestic shorthair cats were randomly assigned to either serve as non-treated controls or were treated topically with a minimum of 40mg/kg metaflumizone in single spot-on Day 0. On Days -2, 7, 14, 21, 28, 35, 42, 49, and 56, each cat was infested with approximately 100 unfed cat fleas, Ctenocephalides felis felis. On Days 1, 2, and 3, and at 48 and 72h after each post-treatment reinfestation, flea eggs were collected and counted. At approximately 72h after treatment or infestation, each cat was combed to remove and count live fleas. Egg viability was determined by examining hatched eggs after 5 days and adult emergence was determined 28 days after egg collection. Metaflumizone provided >/=99.6% efficacy against adult fleas from Days 3 to 45 following a single application. Following treatment, egg production fell by 51.6% within 24h and 99.2% within 48h. Following subsequent weekly infestations egg production from treated cats was negligible out to Day 38, with >/=99.5% reduction relative to non-treated cats. Where there were eggs to evaluate, metaflumizone treatment did not have any apparent effect on the hatching of eggs or on the development and emergence of adult fleas from the eggs produced by fleas from treated animals.

Topics: Administration, Topical; Animals; Cat Diseases; Cats; Ectoparasitic Infestations; Female; Insecticides; Life Cycle Stages; Male; Oviposition; Parasite Egg Count; Random Allocation; Semicarbazones; Siphonaptera

A novel spot-on formulation containing metaflumizone plus amitraz (ProMeris/ProMeris Duo for Dogs, Fort Dodge Animal Health, Overland Park, KS) was evaluated in four laboratory studies to confirm efficacy against fleas and ticks on dogs for 1 month. Three different strains of cat flea (Ctenocephalides felis felis) and four tick species were used. Rhipicephalus sanguineus and Dermacentor variabilis were evaluated concurrently in two studies and Ixodes scapularis and Amblyomma americanum in one study each. In all studies, dogs were randomly allocated to treatment groups and compared with nontreated dogs. One study also included a placebo treatment and a commercial product containing fipronil plus S-methoprene. All treatments were applied to the skin at a single spot between the scapulae on Day 0. Dogs were infested with fleas and/or ticks prior to treatment and then reinfested at weekly intervals for 6 weeks after treatment and evaluated for efficacy at 1 or 2 days after treatment and each reinfestation. These studies confirmed that treatment with ProMeris for Dogs at the proposed commercial dose rate rapidly controlled existing infestations of fleas and ticks on dogs. Treatment provided control of reinfesting fleas for up to 6 weeks and at least 4 weeks control of ticks. Efficacy was confirmed in a variety of dog breeds against three different flea strains and four common species of ticks found on dogs in the United States.

Topics: Animals; Dog Diseases; Dogs; Drug Combinations; Ectoparasitic Infestations; Female; Insect Control; Insecticides; Ixodidae; Male; Semicarbazones; Siphonaptera; Tick Control; Tick Infestations; Toluidines

Four laboratory studies were conducted in Beagle dogs to evaluate the safety of a novel ectoparasiticide combination of metaflumizone plus amitraz (ProMeris/ProMeris Duo for Dogs, Fort Dodge Animal Health, Overland Park, KS) when applied according to the recommended dosage of >/=20mgmetaflumizonekg(-1) plus >/=20mgamitrazkg(-1), at exaggerated and repeated dosages, and if accidentally orally ingested. Parameters evaluated included body weight, food consumption, clinical, physical and neurological examinations, clinical pathology and gross and microscopic pathology. Exaggerated and repeated topical treatment with metaflumizone plus amitraz administered at 1x, 3x and 5x the recommended dose had no effect on clinical findings, heart rates, body weight, food consumption, physical/neurological examinations, macroscopic and microscopic pathology. Very slight, transient, clinically insignificant increases in serum urea nitrogen were noted in some dogs treated at all dose rates tested. This effect was not persistent, was not dose-responsive, nor aggravated by repeated applications and was not associated with a corresponding increase in creatinine or renal pathology. Therefore, these increases in urea nitrogen were suspected to be of non-renal origin and were not considered toxicologically significant. Exaggerated doses (3x and 5x) caused very mild, transient hyperglycemia, most notably in some adult females. Transient and inconsistently noted mild increases in leukocytes, neutrophils and monocytes were observed in some 3x and 5x treated dogs at some intervals. None of the effects noted were aggravated by repeated administration. When 10% of the recommended topical dose was orally administered to mimic exposure due to licking the application, avoidance behaviors including spitting, head shaking, and salivation were noted immediately in all animals. Consequently, voluntary oral ingestion is considered unlikely. Transient decreased activity, slightly reduced body temperature and pale oral mucous membranes were noted in some animals beginning 1-2h posttreatment. Ataxia, resolving within 4h posttreatment, was noted in one female. Oral administration had no effect on clinical pathology. Results from these four studies indicate repeated use of metaflumizone plus amitraz causes no adverse health effects when used as recommended in dogs as young as 8 weeks of age.

Topics: Administration, Topical; Animals; Dog Diseases; Dogs; Drug-Related Side Effects and Adverse Reactions; Ectoparasitic Infestations; Female; Insect Control; Insecticides; Male; Semicarbazones; Tick Control; Tick Infestations; Toluidines

Four laboratory studies were conducted in cats of various ages to evaluate the safety of a novel low-volume topical spot-on containing 20% metaflumizone (ProMeris for Cats, Fort Dodge Animal Health, Overland Park, KS) when used in cats according to the recommended minimum dosage of 40mg metaflumizonekg(-1) delivered via fixed volume doses of 0.8ml for cats 4.0kg. Study parameters included body weight, food consumption, clinical, physical and neurological examinations, and clinical pathology including complete hematology, coagulation, clinical chemistry and urinalysis. Exaggerated and repeated topical applications of metaflumizone at 1x, 3x and 5x the proposed recommended dose in adult cats and kittens 8 weeks of age had no effect on mortality, body weight, food consumption, clinical, physical or neurological examinations, or clinical pathology parameters. Transient salivation was sporadically noted following some, but not all treatment applications. It occurred and resolved within minutes of treatment application in all groups, including cats treated with placebo. Consequently, it was not considered a direct result of treatment with the active ingredient, metaflumizone. Cats orally administered 10% of the recommended topical dose exhibited considerable avoidance behaviors including spitting, head shaking, and salivation. Therefore, voluntary oral exposure is unlikely. No other adverse signs were observed. Repeated use of metaflumizone caused no adverse health effects when administered at 5x the recommended dose and is safe when used as directed, even on kittens as young as 8 weeks of age.

Topics: Administration, Oral; Administration, Topical; Alkaline Phosphatase; Animals; Blood Cells; Body Weight; Cat Diseases; Cats; Ectoparasitic Infestations; Female; Insect Control; Insecticides; Male; Semicarbazones

A novel spot-on formulation containing metaflumizone and amitraz (ProMeris/ProMeris Duo for Dogs, Fort Dodge Animal Health, Overland Park, KS) was evaluated in a laboratory study to determine the appropriate dose for efficacy against fleas and ticks on dogs for 1 month. Thirty-six Beagles were randomly allocated to six equal groups and individually housed. One group remained nontreated. Another was treated with a placebo formulation (solvents with no active ingredients). Three groups of dogs were treated topically with the metaflumizone plus amitraz formulation (150mg of each of metaflumizone and amitraz/ml), at volumes providing doses of 10, 20 and 40mgeachactive/kg. The final group was treated with a commercial spot-on providing 6.7mgfipronil/kg. All treatments were applied to the skin at a single spot between the scapulae on Day 0. Dogs were infested with 50 adult brown dog ticks (Rhipicephalus sanguineus) on each of Days -2, 5, 12, 19, 26, 33 and 40, and with 100 cat fleas (Ctenocephalides felis felis) on Days -1, 6, 13, 20, 27, 34 and 41. Dogs were examined and parasites "finger counted" on Day 1 to estimate knock down efficacy, and all animals were comb counted to determine the numbers of viable fleas and ticks on Days 7, 14, 21, 28, 35 and 42. There were no significant differences in parasite counts between the nontreated control and the placebo-treated control groups for either fleas or ticks (P>0.05) except for very slight reductions on Day 7 for fleas and Day 14 for ticks, demonstrating that the formulation excipients had no activity. The qualitative finger counts on Day 1 indicated that all of the insecticidal treatments resulted in a noticeable reduction in flea and tick numbers within 1 day of treatment. All of the metaflumizone and amitraz treatments and fipronil resulted in significantly lower flea and tick numbers relative to nontreated controls on all posttreatment count days (P<0.05). For the metaflumizone plus amitraz treatments, mean flea and tick counts for the 10mg/kg dose were significantly higher than those for the 20mg/kg dose (P<0.05) from Day 21 on. There was no significant advantage provided by the 40mg/kg dose over the 20mg dose throughout the entire study (P>0.05). The two higher metaflumizone plus amitraz doses provided >95% control of fleas and >90% control of ticks for at least 35 days after treatment, and this level of control was similar to that of the commercial fipronil product. The 20mg/kg dose was selected as the min

Topics: Administration, Topical; Animals; Dog Diseases; Dogs; Drug Combinations; Ectoparasitic Infestations; Insect Control; Insecticides; Rhipicephalus sanguineus; Semicarbazones; Siphonaptera; Tick Control; Tick Infestations; Toluidines

A novel spot-on formulation containing metaflumizone (ProMeris for Cats, Fort Dodge Animal Health, Overland Park, KS) was evaluated in five laboratory studies to determine the duration of residual efficacy in cats against fleas after a single spot treatment. In each study, eight domestic shorthair cats were randomly allocated to each treatment group and individually housed. One group in each study remained non-treated. In one study, an additional group of eight cats was treated with a placebo formulation. Cats were treated topically with metaflumizone formulation to provide a dose of at least 40mg metaflumizone/kg. Cats were infested with 100 cat fleas (Ctenocephalides felis felis) once per week for approximately 8 weeks. Cats were comb counted 48h after treatment and each infestation to determine the number of viable fleas present. There were no significant differences in flea counts between the non-treated control and the placebo-treated control (P>0.05) other than a 26% reduction at week 1, demonstrating that the formulation excipients had no activity. Metaflumizone treatment resulted in significantly lower flea numbers relative to non-treated controls on all post-treatment count days (P<0.05). Metaflumizone provided >90% control of flea infestations up to 7 weeks following a single treatment.

Topics: Animals; Cat Diseases; Cats; Ectoparasitic Infestations; Female; Insect Control; Insecticides; Male; Semicarbazones; Siphonaptera

The efficacy and safety of a novel spot-on formulation of metaflumizone (ProMeris for Cats, Fort Dodge Animal Health, Overland Park, KS) was assessed in cats naturally infested with fleas in a multiregional, clinical field study. Sixteen veterinary clinics in Germany and eight clinics in France enrolled patients to the study. A total of 173 cats with flea infestation qualified as primary patients and were randomly allocated to one of the two treatments in a ratio of approximately 2:1 for metaflumizone (minimum dosage of 40mg/kg) or fipronil (at the recommended label rate). Clinical examinations and baseline parasite counts were performed on Day 0 prior to treatment. Flea counts and safety evaluations were repeated at approximately 2-week intervals for 8 weeks. Both treatments resulted in consistent reductions (>84%) in flea numbers throughout the study, but metaflumizone resulted in numerically higher reductions on most count days. Within groups the flea reduction was highly significant (p<0.0001) compared to baseline at all observation periods. The efficacy of metaflumizone against fleas compared to baseline was 91.0%, 89.4%, 90.8% and 90.7% at Day 14, 28, 42 and 56, respectively. The corresponding efficacies for fipronil were 91.7%, 86.9%, 84.6% and 87.7%. Metaflumizone was highly effective in controlling existing infestations of fleas on cats and was effective against reinfestation for at least 56 days. Metaflumizone showed a good tolerance profile in cats.

Topics: Animals; Cat Diseases; Cats; Drug-Related Side Effects and Adverse Reactions; Ectoparasitic Infestations; Europe; Female; Insecticides; Male; Pyrazoles; Semicarbazones; Siphonaptera; Water

The efficacy and safety of a novel spot-on formulation of metaflumizone plus amitraz (ProMeris/ProMeris Duo for Dogs, Fort Dodge Animal Health, Overland Park, KS) was assessed in dogs naturally infested with ticks and/or fleas in a multiregional, clinical field study. Nineteen veterinary clinics in Germany and 11 clinics in France enrolled patients to the study. One hundred eighty one dogs with tick infestation and 170 dogs with flea infestation (plus three dogs harboring both ticks and fleas) qualified as primary patients and were randomly allocated to one of two treatments in a ratio of approximately 2:1 for metaflumizone plus amitraz (minimum dosage of 20 plus 20mg/kg) or fipronil (at the recommended label rate). Clinical examinations and baseline parasite counts were performed on Day 0 prior to treatment. Tick and/or flea counts and safety evaluations were repeated at intervals of about 2 weeks for 8 weeks. Both products resulted in consistent reductions in tick numbers (>81%) throughout the study, with metaflumizone plus amitraz giving consistently higher reductions in tick numbers. The efficacy against tick count compared with Day 0 was 97.6%, 93.5%, 89% and 94% at Day 14, 28, 42 and 56, respectively, for metaflumizone plus amitraz. The corresponding efficacies for fipronil were 86.3%, 81.1%, 84.8% and 86.1%. Within groups, the tick reduction was highly significant (P<0.0001) compared to baseline at all observation periods. Both treatments resulted in consistent (>89%) and highly significant (P<0.0001) reductions in flea numbers relative to the baseline counts throughout the study, although fipronil resulted in numerically higher reductions on each count day. The efficacy against fleas compared to baseline was 91.8%, 88.7%, 91.5% and 92.0% at Day 14, 28, 42 and 56, respectively, for metaflumizone plus amitraz. The corresponding efficacies for fipronil were 98.2%, 96.3%, 95.9% and 96.7%. Metaflumizone plus amitraz was highly effective in controlling existing infestations of fleas and ticks on dogs and was effective against reinfestation for at least 56 days. Metaflumizone plus amitraz showed a good tolerance profile in dogs.

Topics: Animals; Dog Diseases; Dogs; Drug Combinations; Drug-Related Side Effects and Adverse Reactions; Ectoparasitic Infestations; Europe; Female; Insecticides; Male; Pyrazoles; Random Allocation; Semicarbazones; Tick Infestations; Toluidines; Water

A topical spot-on solution was developed for treating pets that contained of active ingredients metaflumizone and amitraz and intended for use as an ectoparasiticide. The formulation vehicle system was designed by balancing the following three attributes of various solvents: evaporation/drying, surface spreading, and percutaneous absorption. The solvents were selected by evaluating the solubilization capacity of individual solvents with respect to the above active ingredients. The evaporation rates of various solvent systems were then determined. The visual observations of the treatment sites was also performed a day after treating the dogs to understand the cosmetic effect of various solvent systems. The lead formulations dried off within a day after application with no noticeable residue at the treatment site, while others produced appreciable powdery residue or a large wet and oily spot. The stability of the lead formulations was also evaluated over 2 years to demonstrate a 2-year shelf life of this product.

Topics: Administration, Topical; Animals; Dog Diseases; Dogs; Drug Combinations; Drug Stability; Ectoparasitic Infestations; Female; Insecticides; Male; Semicarbazones; Solubility; Solvents; Tick Infestations; Time Factors; Toluidines

Spot-on formulations of metaflumizone and a combination of fipronil-(S)-methoprene were evaluated in adult cats to determine the duration of 24- and 48-hour efficacy and short-term speed of kill against adult cat fleas, Ctenocephalides felis felis. Speed of kill efficacies (at 12, 18, 24, and 48 hours) were assessed against existing (day -1) infestations and against infestations at day 7, and efficacy was assessed 24 and 48 hours after weekly flea infestations through day 42. Cats treated with fipronil-(S)-methoprene had significantly (P<.01) fewer fleas than those treated with metaflumizone at 12 and 18 hours after treatment (day 0) and on the day 7 infestations. Fipronil-(S)-methoprene-treated cats also had significantly (P<.05) fewer fleas than metaflumizone-treated cats for all 24-hour counts from initial treatment on day 0 through infestation day 42 and for the 48-hour counts on day 28 through day 42.

Topics: Administration, Topical; Animals; Cat Diseases; Cats; Ectoparasitic Infestations; Female; Insecticides; Male; Methoprene; Pyrazoles; Semicarbazones; Siphonaptera; Time Factors; Treatment Outcome

Four active ingredients--imidacloprid selamectin, fipronil-(S)-methoprene, and metaflumizone--were tested to assess the speed of flea kill against existing flea infestations and subsequent reinfestations. Thirty flea-infested cats were allocated to four treatment groups and one untreated control group. Flea counts were performed 6, 18, and 48 hours after treatment (day 0) and 2, 4, and 24 hours after weekly flea reinfestations. Cats were also reinfested with fleas after the 6- and 18-hour counts on day 0 and after the 2- and 4-hour counts on subsequent count days. Imidacloprid provided significantly greater flea kill at diverse time points. At the 24-hour counts, all compounds showed expected and similar high efficacies. On study day 34, imidacloprid showed the highest efficacy at 24 hours after reinfestation, with 90.8% flea reduction compared with 55.7% to 67.4% in the other treatment groups. A single topical application of imidacloprid provided a high efficacy in the early elimination of adult fleas, limiting the risk of pathogen transmission and flea allergy dermatitis.

Topics: Administration, Topical; Animals; Cat Diseases; Cats; Ectoparasitic Infestations; Female; Imidazoles; Insecticides; Ivermectin; Male; Methoprene; Neonicotinoids; Nitro Compounds; Parasite Egg Count; Pyrazoles; Random Allocation; Semicarbazones; Siphonaptera; Time Factors; Treatment Outcome

A spot-on metaflumizone formulation was evaluated in adult domestic short hair cats to determine its adultidical efficacy against a flea strain that has reduced susceptibility to a number of insecticides. Eight cats served as non-treated controls, eight cats were treated with a metaflumizone formulation at 0.2 ml/kg (40 mg metaflumizone/kg) and eight cats were treated with fipronil 10% w/v-(s)-methoprene 12%w/v at 0.075 ml/kg (7.5-7.7 mg fipronil/kg:9.0-9.2 mg (s)-methoprene/kg). On days -1, 7, 14, 21, 28, 35, and 42 each cat was infested with approximately 100 unfed KS1 cat fleas, Ctenocephalides felis. At approximately 48 h after treatment or infestation, each cat was combed to remove and count live fleas. Treatment with metaflumizone provided > or = 99.3% efficacy for 3 weeks post-treatment and then 97.4, 91.4 and 86.2% efficacy at 4, 5 and 6 weeks post-treatment, respectively. Fipronil-(s)-methoprene provided 99.6% efficacy at 1 week post-treatment and then 97.6, 96.4, 71.3, 22.0 and 13.1% efficacy at weeks 2, 3, 4, 5 and 6, respectively. The reductions in flea numbers were significantly greater for the metaflumizone treatment than for fipronil-(s)-methoprene from 3 to 6 weeks after treatment.

Topics: Administration, Topical; Animals; Cat Diseases; Cats; Dose-Response Relationship, Drug; Drug Resistance; Ectoparasitic Infestations; Female; Insect Control; Insecticides; Male; Pyrazoles; Random Allocation; Semicarbazones; Siphonaptera; Time Factors; Treatment Outcome

Topics: Animal Diseases; Animals; Ectoparasitic Infestations; Insecticides; Semicarbazones; Veterinary Medicine