Evaluation of the efficacy and safety of a novel formulation of metaflumizone in cats naturally infested with fleas in Europe.

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.

Evaluation of the efficacy and safety of a novel formulation of metaflumizone plus amitraz in dogs naturally infested with fleas and ticks in Europe.

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.

Pharmacokinetics of metaflumizone and amitraz in the plasma and hair of dogs following topical application.

Controlled laboratory studies have shown that a metaflumizone plus amitraz combination (ProMeris/ProMeris Duo for Dogs, Fort Dodge Animal Health, Overland Park, KS) applied topically is effective for the treatment and control of fleas and ticks on dogs. Two studies were conducted to determine the distribution of both metaflumizone and amitraz in the plasma and hair of dogs following treatment at the minimum recommended dose of approximately 20mg/kg of each active ingredient. Six purpose-bred, adult Beagle dogs were used in each study. Plasma or hair samples were collected from each dog just prior to dosing and periodically through 56 days after treatment. Samples were analyzed by HPLC methods validated for the simultaneous determination of metaflumizone and amitraz. Amitraz was detectable (>3.2ng/ml) but not quantifiable (<50ng/ml) in only two plasma samples, collected 1 and 2 days post-treatment from different dogs. Metaflumizone concentrations in plasma were generally detectable (>1.0ng/ml) but not quantifiable (<50ng/ml). Measurable levels were found in one dog 7 days post-treatment, increasing to a maximum of four dogs at 42 days after dosing, with a metaflumizone range of 59-138ng/ml. Analysis of hair samples indicated that both metaflumizone and amitraz were widely distributed at basically similar levels in the hair within 1-day after administration, reaching maximum concentrations between 2 and 7 days post-treatment. Low but quantifiable levels of both compounds were still present on hair at the end of the 56-day study. These studies indicate that the ectoparasitic activity is due to exposure of the parasites to metaflumizone and amitraz on the surface of the host (hair and/or skin), not to exposure via the circulatory system of the host.

Pharmacokinetics of metaflumizone in the plasma and hair of cats following topical application.

Controlled laboratory studies have shown that a novel spot-on formulation containing 20% (w/v) metaflumizone (ProMeris for Cats, Fort Dodge Animal Health, Overland Park, KS) is effective for the treatment and control of fleas on cats. Two studies were conducted to determine the distribution of metaflumizone in the plasma and hair of cats following treatment at the minimum recommended dose of 40mg/kg. Six purpose-bred cats, three males and three females, were used in each study. Plasma or hair samples were collected from each cat just prior to dosing and periodically through 56 days after treatment. Samples were analyzed by HPLC methods validated for the determination of metaflumizone. Metaflumizone concentrations in plasma were below the method limit of quantification (<50ng/ml) in all samples but one, and were frequently not detectable (<1.1ng/ml). Plasma collected 3 days post-treatment from one cat had a metaflumizone concentration of 57.8ng/ml. The frequency of measurable levels of metaflumizone in the plasma was too low to allow the calculation of pharmacokinetic parameters. Analysis of hair samples indicated that metaflumizone was widely distributed in the hair coat of the cat within 1 day after administration, reaching maximum concentrations within 1 or 2 days post-treatment. Low but quantifiable levels were still present at the end of the 56-day study. Data from the present studies indicate that the ectoparasitic activity is due to exposure of the parasites to metaflumizone on the surface of the host (skin and hair), not to exposure via the circulatory system of the host.

Dose determination of the persistent activity of moxidectin long-acting injectable formulations against various nematode species in cattle.

The effectiveness, safety and production-enhancing benefit (improved weight gains) of moxidectin long-acting injection given subcutaneously in the ear at the rates of 0.75, 1.0 and 1.5mg/kg bw were evaluated in three studies under common protocol. The only adverse reaction to treatment was a mild (<2 tablespoons in volume), and for the most part transient (<28 days for the treatment rate of 1.0mg/kg bw) injection site swelling as noted in a minority of the animals (12.2% of the animals treated at the rate of 1.0mg/kg bw). Regardless of study site, post-treatment interval or dose rate, average daily gains were improved over control cattle by approximately 33%. Reductions in strongyle EPG counts relative to controls were > or = 90% for all dose rates of moxidectin for a post-treatment period of 42 days (Wisconsin), 84 days (Arkansas) and 140 days (Louisiana). In Arkansas and Louisiana, the majority (>80%) of post-treatment strongyle eggs, as determined by coproculture, were Cooperia spp. As determined by sequential necropsies, periods of continuous, post-treatment protection (> or = 90% efficacy in at least two out of three studies) for moxidectin long-acting injection given at the rate of 1.0 mg/kg bw were 90 days (adult Haemonchus spp.), 120 days (Dictyocaulus viviparus and adult Ostertagia and Oesophagostomum) and 150 days (Ostertagia spp. EL4).

Effects of cimaterol, a beta-adrenergic agonist, on protein metabolism in rats.

Fractional accretion rates of total body 3-methylhistidine containing proteins (actin and myosin) were elevated 40% to 120% in rats fed a high-carbohydrate diet containing 10 or 100 ppm cimaterol for 1 week. Fractional degradation and fractional synthesis rates of these proteins were examined by measuring total body 3-methylhistidine content and urinary excretion of 3-methylhistidine. Consumption of the diet containing 100 ppm cimaterol for 1 week caused a 25% reduction in fractional degradation rates and a concomitant 32% increase in fractional synthesis rates of 3-methylhistidine containing proteins. Effects of cimaterol on fractional accretion, degradation, and synthesis rates of 3-methylhistidine containing proteins diminished after 1 week. Cimaterol failed to influence plasma insulin, triiodothyronine, or corticosterone concentrations. The dramatic increase in accretion of 3-methylhistidine containing proteins observed during the first week rats are fed diets containing cimaterol is caused by reciprocal action on protein degradation and synthesis.

Effects of cimaterol, a beta-adrenergic agonist, on lipid metabolism in rats.

Rats fed a high carbohydrate diet containing 10 or 100 ppm cimaterol for 4 weeks gained 41% to 59% less fat and 70% to 76% more protein than controls, with no major changes in either energy gain or efficiency of energy retention. Effects of cimaterol on lipid metabolism in these rats were assessed. Cimaterol stimulated lipolysis in vivo and in vitro, but failed to influence rates of de novo fatty acid synthesis in either liver or white adipose tissue. Activities of fatty acid synthetase and malic enzyme in these tissues were also unaffected by cimaterol. Cimaterol administered in vivo failed to affect lipoprotein lipase activity in white adipose tissue, but elevated enzyme activity 67% to 75% in the extensor digitorium longus muscle. Lipoprotein lipase activity in the extensor digitorum longus muscle was also elevated by 66% during a 2 hour incubation with 1 mmol/L cimaterol. We conclude that cimaterol selectively stimulates both lipolysis in white adipose tissue and lipoprotein lipase activity in skeletal muscle, to direct energy away from adipose tissue deposition toward skeletal muscle accretion.

Efficacy, safety, and residue evaluation of levamisole gel formulation in sows.

Anthelmintic efficacy, safety, and residue studies were conducted in sows and gilts with a levamisole gel containing 11.5% levamisole HCl. In 12 sows and 12 gilts, 8 mg of levamisole HCl equivalent/kg of body weight orally was 100% (resinate) and 91.1% (gel) effective against 55-day-old Ascaris suum and 100% (gel) and 96.1% (resinate) effective against Oesophagostomum dentatum. In 20 sows given levamisole gel (8 mg of levamisole HCl/kg) orally just before breeding, 4 to 6 weeks after breeding, 4 to 6 weeks before farrowing, and just before farrowing, there were no adverse effects. Transient salivation was noticed in five sows after treatment. In 4 groups of 4 sows each given levamisole gel orally to provide 8, 24, 40, or 80 mg of levamisole HCl/kg, adverse clinical signs were not observed in sows treated with 8 mg/kg. Transient salivation was noticed in one sow given 24 mg/kg, two sows given 40 mg/kg, and four sows given 80 mg/kg. Multiple emesis and chomping occurred in one sow given 80 mg/kg. Levamisole residues in edible tissues from sows given 8 mg of levamisole gel/kg orally were less than 0.1 mg/kg of muscle and fat in sows killed on posttreatment day (PTD) 3 and less than 0.1 mg/kg of kidney in sows killed on PTD 5. Liver residues averaged 0.78 mg/kg in sows killed on PTD 3 and were reduced to 0.31 mg/kg in sows killed on PTD 5. The 99% upper tolerance limit with 95% confidence on the withdrawal time to assure levamisole residues of less than 0.10 mg/kg in liver tissue was 11 days.