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.

Efficacy of moxidectin 2% equine gel against natural nematode infections in ponies.

The efficacy of moxidectin 2% oral gel (Equest, Fort-Dodge) against European worm strains was studied through post-mortem worm counts and feacal egg counts (FECs) in 12 young ponies naturally infected. The animals were allocated in two groups of six ponies each: the first one was treated at 0.4 mg/kg b.w. and the second one received a placebo and served as control. All the ponies were necropsied 14 days post-treatment. The efficacy of moxidectin in reducing strongyle FECs ranged from 99.8% to 100% from 3 to 14 days after treatment. Moxidectin efficacy was 100% against Trichostrongylus axei and Triodontophorus spp., > 99.9% against Cyathostomes adults and L5, 92% against S. edentatus L5, 100% against O. equi L5, 99% against O. equi L4, and 92% against G. intestinalis. No animal treated with moxidectin was harbouring P. equorum, Habronema spp., G. pecorum nor G. nasalis, while the control group was slightly infected with these parasites. This experiment confirms the post-mortem worm count results obtained in the United States and the FECs results reported in Europe. Moxidectin showed to be safe in young ponies.

Persistent efficacy of topical moxidectin against Dictyocaulus viviparus and Ostertagia ostertagi.

The persistent activity of moxidectin topically administered at the dose rate of 0.5 mg kg-1 bodyweight was evaluated against experimental nematode infection in 30 calves randomly allocated to six groups. Five groups were treated on days -42, -35, -28, -21 and -14. The 6th group remained untreated as a control. On Day 0, the calves were infected experimentally with 1000 Dictyocaulus viviparus and 50,000 Ostertagia ostertagi larvae and killed 3 weeks later. The formulation of moxidectin showed excellent activity against both parasites for up to 5 weeks (> 99%). Six weeks after treatment the reduction in the number of D. viviparus was still high (> 90%). No adverse reactions to moxidectin were observed in any of the animals.

The persistence of the efficacy of injectable or oral moxidectin against Teladorsagia, Haemonchus and Trichostrongylus species in experimentally infected sheep.

The persistence of the efficacy of moxidectin was evaluated against experimental gastrointestinal nematode infections in 55 lambs randomly allocated to 11 equal groups and infected on day 0. Moxidectin 1 per cent injectable solution was administered at a dose rate of 0.2 mg moxidectin/kg bodyweight to five of the groups on days -42, -35, -28, -21 and -14; five other groups were treated with moxidectin 0.1 per cent oral drench at the same dose rate on days -35, -28, -21, -14 and -7, and the 11th group remained untreated as a control. The lambs were infected experimentally with 8000 Teladorsagia circumcincta, 2000 Haemonchus contortus and 10,000 Trichostrongylus colubriformis infective larvae and killed three weeks later. Both formulations of moxidectin showed excellent activity against T circumcincta and H contortus with almost 100 per cent efficacy against the abomasal parasites for up to 35 days after treatment. The efficacy of moxidectin 1 per cent injectable against T colubriformis was much higher (> 99 per cent) than that of the oral drench and it was highly effective up to 21 days after treatment, and gave a moderate reduction in worm burden for up to 35 days after treatment. No adverse reactions to moxidectin were observed in any of the animals.