Cyathostome fecal egg count trends in horses treated with moxidectin, ivermectin or fenbendazole

Commercial preparations of fenbendazole (Safe-Guard, Intervet), ivermectin (Eqvalan, Merial) or moxidectin (Quest, Fort Dodge) were administered once to horses scheduled for routine parasiticide treatment. In total, 93 horses from six cooperating farms were used in the study. Computer generated, random allocation of horses to treatment group was conducted at each farm. Fecal egg counts were determined for all horses on trial days 0, 56, 84 and 112, with corresponding calendar dates that were unique to each farm. Only strongyle egg counts from animals which were positive at day 0 were used for analysis of variance and comparisons. Counts for the three treatment groups were similar at day 0, moxidectin相似文献   

Faecal excretion profile of moxidectin and ivermectin after oral administration in horses

A study was undertaken to evaluate and compare faecal excretion of moxidectin and ivermectin in horses after oral administration of commercially available preparations. Ten clinically healthy adult horses, weighing 390-446 kg body weight (b.w.), were allocated to two experimental groups. Group I was treated with an oral gel formulation of moxidectin at the manufacturer's recommended therapeutic dose of 0.4 mg/kg b.w. Group II was treated with an oral paste formulation of ivermectin at the recommended dose of 0.2 mg/kg b.w. Faecal samples were collected at different times between 1 and 75 days post-treatment. After faecal drug extraction and derivatization, samples were analysed by High Performance Liquid Chromatography using fluorescence detection and computerized kinetic analysis.For both drugs the maximum concentration level was reached at 2.5 days post administration. The ivermectin treatment groups' faecal concentrations remained above the detectable level for 40 days (0.6 +/- 0.3 ng/g), whereas the moxidectin treatment group remained above the detectable level for 75 days (4.3 +/- 2.8 ng/g). Ivermectin presented a faster elimination rate than moxidectin, reaching 90% of the total drug excreted in faeces at four days post-treatment, whereas moxidectin reached similar levels at eight days post-treatment. No significant differences were observed for the values of maximum faecal concentration (C(max)) and time of C(max)(T(max)) between both groups of horses, demonstrating similar patterns of drug transference from plasma to the gastrointestinal tract. The values of the area under the faecal concentration time curve were slightly higher in the moxidectin treatment group (7104 +/- 2277 ng.day/g) but were not significantly different from those obtained in the ivermectin treatment group (5642 +/- 1122 ng.day/g). The results demonstrate that although a 100% higher dose level of moxidectin was used, attaining higher plasma concentration levels and more prolonged excretion and gut secretion than ivermectin, the concentration in faeces only represented 44.3+/- 18.0% of the total parental drug administered compared to 74.3 +/- 20.2% for ivermectin. This suggests a higher level of metabolization for moxidectin in the horse.     

Comparative long-term efficacy of ivermectin and moxidectin over winter in Canadian horses treated at removal from pastures for winter housing

The impact of a late fall treatment on the spring rise of fecal egg counts was evaluated in a controlled study with Canadian horses treated with 2 different dewormers immediately after removal from pasture for winter housing. The horses were stabled until the end of the trial period. Seventeen weanlings, 20 yearlings, and 15 2-year-old horses located in Ontario, which were presumed to be naturally infected with cyathostomins after pasture grazing, were randomly allocated to either a group treated with 0.4 mg/kg of moxidectin and 2.5 mg/kg of praziquantel or a group treated with 0.2 mg/kg of ivermectin and 1.5 mg/kg of praziquantel. Three weeks after treatment, all strongyle fecal egg counts were reduced to zero for both treatment groups. However, at 5 months post-treatment, mean geometric fecal egg counts were statistically higher for the yearlings and 2-year-old horses treated with ivermectin than for the yearlings and 2-year-old horses treated with moxidectin (P < 0.0001).     

Field evaluation of moxidectin/praziquantel oral gel in horses

The safety and efficacy of 2% moxidectin/12.5% praziquantel oral gel administered at a rate of 0.4 mg moxidectin and 2.5 mg praziquantel/kg was studied in client-owned horses under field use conditions. Four hundred horses (300 treated with moxidectin/praziquantel oral gel and 100 treated with vehicle) were enrolled, feces were collected, and eggs were counted. Investigators as well as horse owners were masked to treatment assignment. No adverse reactions to treatment were observed in any horses. Moxidectin/praziquantel gel reduced Anoplocephala spp by more than 99% and provided a significant (P <.05) reduction (> 98%) in the strongyle egg count of treated horses.     

Antiparasitic activity of an ivermectin and praziquantel combination paste in horses

Modern anthelmintic use in horses has decreased the prevalence of the large strongyles, which has in turn shifted the focus of parasitologists to the pathogenic importance of the small strongyles, tapeworms, and other parasites. These studies show that a combination product containing ivermectin and praziquantel allowed efficacious treatment of horses for nematode, cestode, and bot infections. The use of this combination product may be of special benefit to horses that are mainly kept outdoors and on grazing pastures.     

Comparative plasma disposition kinetics of ivermectin, moxidectin and doramectin in cattle

The persistence of the broad-spectrum antiparasitic activity of endectocide compounds relies on their disposition kinetics and pattern of plasma/tissues exchange in the host. This study evaluates the comparative plasma disposition kinetics of ivermectin (IVM), moxidectin (MXD) and doramectin (DRM) in cattle treated with commercially available injectable formulations. Twelve (12) parasite-free male Hereford calves (180–210 kg) grazing on pasture were allocated into three groups of four animals each. Animals in each group received either IVM (Ivomec 1%, MSD AGVET, Rahway, NJ, USA), MXD (Cydectin 1%, American Cyanamid, Wayne, NJ, USA) or DRM (Dectomax 1%, Pfizer Inc., New York, NY, USA) by subcutaneous injection at a dose of 200 μg/kg. Jugular blood samples were collected from 1 h up to 80 days post-treatment, and plasma extracted, derivatized and analysed by high performance liquid chromatography (HPLC) using fluorescence detection. The parent molecules were detected in plasma between 1 h and either 70 (DRM) or 80 (IVM and MXD) days post-treatment. The absorption of MXD from the site of injection was significantly faster (absorption half-life (t_½ab) = 1.32 h) than those of IVM (t_½ab= 39.2 h) and DRM (t_½ab= 56.4 h). MXD peak plasma concentration (C_max) was reached significantly earlier (8.00 h) compared to those of IVM and DRM (4–6 days post-treatment). There were no differences on C_max values; the area under the concentration–time curve (AUC) was higher for IVM (459 ng.d/mL) and DRM (627 ng.d/mL) compared to that of MXD (217 ng.d/mL). The mean plasma residence time was longer for MXD (14.6 d) compared to IVM (7.35 d) and DRM (9.09 d). Unidentified metabolites were detected in plasma; they accounted for 5.75% (DRM), 8.50% (IVM) and 13.8% (MXD) of the total amount of their respective parent drugs recovered in plasma. The comparative plasma disposition kinetics of IVM, MXD and DRM in cattle, characterized over 80 days post-treatment under standardized experimental conditions, is reported for the first time.     

Control of endoparasites in horses with a gel containing moxidectin and praziquantel

A gel formulation containing moxidectin (20 g/kg) and praziquantel (125 g/kg) reduced the geometric mean faecal strongyle egg count in horses to below 100 eggs per gram of faeces (epg) for at least 12 weeks despite their being exposed continuously to reinfection from pasture grazed by treated and untreated horses. The geometric mean egg count of horses treated with a proprietary paste containing abamectin (3.7 g/kg) and praziquantel (46.2 g/kg) increased steadily from six weeks after the treatment, peaking at over 820 epg after 12 weeks. Relative to the efficacy of the abamectin/praziquantel treatment, the reduction in mean faecal egg count compared with the pretreatment counts was significantly (P<0.05) better in the horses treated with moxidectin and praziquantel from eight weeks after the treatment. Both products eliminated tapeworms from horses in a non-invasive modified critical trial.     

Plasma pharmacokinetics and faecal excretion of ivermectin, doramectin and moxidectin following oral administration in horses

The present study was carried out to investigate whether the pharmacokinetics of avermectins or a milbemycin could explain their known or predicted efficacy in the horse. The avermectins, ivermectin (IVM) and doramectin (DRM), and the milbemycin, moxidectin (MXD), were each administered orally to horses at 200 microg/kg bwt. Blood and faecal samples were collected at predetermined times over 80 days (197 days for MXD) and 30 days, respectively, and plasma pharmacokinetics and faecal excretion determined. Maximum plasma concentrations (Cmax) (IVM: 21.4 ng/ml; DRM: 21.3 ng/ml; MXD: 30.1 ng/ml) were obtained at (tmax) 7.9 h (IVM), 8 h (DRM) and 7.9 h (MXD). The area under the concentration time curve (AUC) of MXD (92.8 ng x day/ml) was significantly larger than that of IVM (46.1 ng x day/ml) but not of DRM (53.3 ng x day/ml) and mean residence time of MXD (17.5 days) was significantly longer than that of either avermectin, while that of DRM (3 days) was significantly longer than that of IVM (2:3 days). The highest (dry weight) faecal concentrations (IVM: 19.5 microg/g; DRM: 20.5 microg/g; MXD: 16.6 microg/g) were detected at 24 h for all molecules and each compound was detected (> or = 0.05 microg/g) in faeces between 8 h and 8 days following administration. The avermectins and milbemycin with longer residence times may have extended prophylactic activity in horses and may be more effective against emerging and maturing cyathostomes during therapy. This will be dependent upon the relative potency of the drugs and should be confirmed in efficacy studies.     

Field efficacy of ivermectin, fenbendazole and pyrantel embonate paste anthelmintics in horses

Three anthelmintic pastes were compared in terms of their ability to suppress the output of parasite eggs in the faeces of 108 grazing horses at four sites in Britain; the horses were treated once with either ivermectin, fenbendazole or pyrantel. At each site, the horses grazed together throughout the trials which took place during the summers of 1985 and 1986. The median periods before parasite eggs reappeared in faeces were 70 days for ivermectin, 14 days for fenbendazole and 39 days for pyrantel embonate. Geometric mean faecal egg counts in the groups treated with ivermectin and pyrantel were significantly less (P less than 0.05) than in the fenbendazole group on days 21, 28, 35 and 42 after treatment. On days 49, 56, 63 and 70 the mean egg counts in the ivermectin group were significantly lower (P less than 0.05) than those in either of the other groups. The results indicated that in order to ensure minimal contamination of pastures, grazing horses treated with ivermectin paste would have required a second treatment approximately 10 weeks after the first, and to achieve similar control with fenbendazole or pyrantel embonate, a second treatment would have been required after approximately two weeks and six weeks, respectively.     

Comparison of the pharmacokinetics of moxidectin (Equest®) and ivermectin (Eqvalan®) in horses

A study was undertaken in order to evaluate and compare plasma disposition kinetic parameters of moxidectin and ivermectin after oral administration of their commercially available preparations in horses. Ten clinically healthy adult horses, weighing 390-446 kg body weight (b.w.), were allocated to two experimental groups of five horses. Group I was treated with an oral gel formulation of moxidectin (MXD) at the manufacturers recommended therapeutic dose of 0.4 mg/kg bw. Group II was treated with an oral paste formulation of ivermectin (IVM) at the manufacturers recommended dose of 0.2 mg/kg b.w. Blood samples were collected by jugular puncture at different times between 0.5 h and 75 days post-treatment. After plasma extraction and derivatization, samples were analysed by HPLC with fluorescence detection. Computerized kinetic analysis was carried out. The parent molecules were detected in plasma between 30 min and either 30 (IVM) or 75 (MXD) days post-treatment. Both drugs showed similar patterns of absorption and no significant difference was found for the time corresponding to peak plasma concentrations or for absorption half-life. Peak plasma concentrations (Cmax) of 70.3+/-10.7 ng/mL (mean +/- SD) were obtained for MXD and 44.0+/-23.1 ng/mL for IVM. Moreover, the values for area under concentration-time curve (AUC) were 363.6+/-66.0 ng x d/mL for the MXD treated group, and 132.7+/-47.3 ng x d/mL for the IVM treated group. The mean plasma residence times (MRT) were 18.4+/-4.4 and 4.8+/-0.6 days for MXD and IVM treated groups, respectively. The results showed a more prolonged residence of MXD in horses as demonstrated by a four-fold longer MRT than for IVM. The longer residence and the higher concentrations found for MXD in comparison to IVM could possibly explain a more prolonged anthelmintic effect. It is concluded that in horses the commercial preparation of MXD presents a pharmacokinetic profile which differs significantly from that found for a commercial preparation of IVM. To some extent these results likely reflect differences in formulation and doses.     

Control of cyathostome infections in mares treated at parturition with ivermectin

Six mares were treated on the day of parturition with an intramuscular injection of 0.2 mg kg-1 ivermectin and placed in a pasture free of equine parasites as soon as possible after foaling. The mares and their foals were compared with a similar group of untreated mares and foals on an adjoining pasture. The experimental data was derived from mare and foal fecal egg counts, foal necropsies and pasture larval counts. Ivermectin administered to mares on the day of parturition, when combined with movement to parasite-free pastures, significantly lowered the cyathostome (small strongyle) egg production for 4 months. This reduced cyathostome exposure was reflected in lower worm-burdens in their foals for 5 months. The results indicate that ivermectin will effectively control equine strongyles when mares and their foals are moved to parasite-free pastures.     

Integrated control of Strongylus vulgaris infection in horses using ivermectin

An attempt was made to control or eliminate Strongylus vulgaris from a closed group of three horses at pasture near Perth, Western Australia, by dosing with ivermectin on four occasions during the time of year when it was believed that environmental conditions would eliminate all the non-parasitic stages of that species. At necropsy, five months after the last dose of anthelmintic and after continually grazing the same pastures, no S vulgaris or arterial lesions were found in those horses and S edentatus, Draschia megastoma and Habronema species were also almost completely eliminated.     

The efficacy and acceptability of ivermectin liquid compared to that of oral paste in horses

One hundred-twenty horses and ponies ranging in age from 142 days to 23 years were used to assess the efficacy and acceptability of ivermectin liquid for horses when given as an oral drench or by nasogastric intubation. Prior to treatment, animals in this study were found to have eggs in the feces of one or more of the following: strongyle type, Parascaris equorum, and Strongyloides westeri. While egg parasite per gram (EPG) numbers from 30 untreated controls remained consistently positive over a 14 day period, parasite EPG numbers from animals treated on Day 0 were reduced to 0 by day 14 as determined by a modified McMaster technique.     

Plasma profiles of ivermectin in horses following oral or intramuscular administration

A study was undertaken in order to evaluate and compare ivermectin's (IVM) plasma disposition kinetic parameters after oral or intramuscular (IM) administration in horses. Ten clinically healthy adult horses, weighing 380-496 kg body weight (BW), were allocated to two experimental groups of five horses. Group I, was treated with an oral paste formulation of IVM at the manufacturer's recommended dose of 0.2 mg/kg BW. Group II, was treated IM with an injectable 1% formulation of IVM at a dose of 0.2 mg/kg BW. Blood samples were collected by jugular puncture at different times between 0.5 h and 75 days post-treatment. After plasma extraction and derivatization, samples were analysed by high-performance liquid chromatography with fluorescence detection. A computerized kinetic analysis was performed, and data were compared using the Wilcoxon signed rank test. The parent molecule was detected in plasma between 30 min and either 20 (oral) or 40 (IM) days post-treatment. Significant differences were found for the time corresponding to peak plasma concentrations (tmax) and for absorption half-life. Peak plasma concentrations (Cmax) of 51.3 +/- 16.1 ng/ml (mean +/- SD) were obtained after oral administration and of 31.4 +/- 6.0 ng/ml for the IM route. The values for area under concentration-time curve were 137.1 +/- 35.9 ng day/ml for the group treated orally, and 303.2 +/- 4.3 ng day/ml for the IM treated group. The mean plasma residence times were 4.2 +/- 0.4 and 8.9 +/- 0.7 days for oral and IM-treated groups, respectively. The results of this study show that the route of administration considerably affects the disposition of IVM. A significant difference in bioavailabilty and half-life of elimination of IVM was observed after IM administration compared with oral administration. A close relationship between pharmacokinetic profiles and the clinical efficacy of IVM was established.     

Searching for ivermectin resistance in Dutch horses

A study was conducted to evaluate the occurrence of resistance against, in particular, ivermectin in cyathostomins in the Netherlands. Seventy horse farms were visited between October 2007 and November 2009. In initial screening, faecal samples were collected 2 weeks after deworming with either ivermectin, moxidectin or doramectin. Pooled faecal samples from a maximum of 10 horses were examined for worm eggs using a modified McMaster technique and for worm larvae after faecal larval cultures. In total 931 horses were involved. On 15 of 70 farms eggs and/or larvae were found. On 8 of these 15 farms a FECRT with ivermectin was performed on 43 horses. Efficacy of ivermectin against cyathostomins of 93% was found in one animal on one farm. Additionally, the strategies and efforts of the horse owners to control cyathostomins, as well as risk factors for the development of macrocyclic lactone resistance were evaluated with a questionnaire. Strikingly, many responders indicated that the control of cyathostomins in horses is achieved through very frequent deworming. Fourteen percent of these owners deworm seven times per year or more. On 34% of the 70 farms treatment was repeated within the Egg Reappearance Period of a product.     

Enhanced plasma availability of moxidectin in fasted horses

The influence of fasting prior to treatment on plasma availability and kinetic disposition of moxidectin was studied in horses. Eight adult crossbred saddle horses were allocated to two experimental groups of four horses. One group was fasted for 24 hours before treatment and the other group received their usual feed. Both groups were treated with an oral gel formulation of moxidectin at the manufacturers recommended therapeutic dose of 0.4 mg/kg. Blood samples were collected by jugular puncture at different times between 0.5 and 50 days. After plasma extraction and derivatization, samples were analyzed by HPLC with fluorescence detection. Computerized pharmacokinetic analyses were done. Fasting induced marked modifications in the pharmacokinetic behavior of moxidectin in the horse. An extended absorption process, and significantly higher area under the curve (AUC) values were obtained in the fasted animals compared to those fed their usual rations. It is suggested that fasting decreases intestinal transit time, and may have prolonged time for absorption of moxidectin. Since, biliary excretion and intestinal secretion are major routes of moxidectin elimination, fasting may have reduced bile flow and intestinal secretion. Fasting before treatment may be a useful tool for improved anthelmintic treatment in horses.     

Comparative pharmacokinetic and pharmacodynamic response of single and double intraruminal doses of ivermectin and moxidectin in nematode-infected lambs

Abstract

AIMS: To compare the pharmacokinetics, distribution and efficacy (pharmacodynamic response) of intraruminal ivermectin (IVM) and moxidectin (MXD) administered at 0.2 and 0.4?mg/kg to naturally nematode-infected lambs, and to determine the ex vivo accumulation of these anthelmintics by Haemonchus contortus.

METHODS: Romney Marsh lambs, naturally infected with IVM-resistant H. contortus, were allocated to treatment groups based on faecal nematode egg counts. They received 0.2 or 0.4?mg/kg IVM or MXD (n=10 per group), or no treatment (Control; n=6), on Day 0. Samples from four animals from each treatment group, including abomasal parasites, were obtained on Day 1. Plasma samples were also collected from Day 0 to 14, and a faecal egg count reduction test (FECRT) and a controlled efficacy trial were carried out on Day 14. Concentrations of IVM and MXD in plasma, in abomasal and intestinal tissues and in H. contortus were evaluated by high-performance liquid chromatography. Additionally, the ex vivo drug accumulation of IVM and MXD by H. contortus was determined.

RESULTS: Peak plasma concentrations and the area under the concentration vs. time curve for both IVM and MXD were higher for 0.4 than 0.2?mg/kg treatments (p<0.05), but there were no differences for other parameters. Concentrations of IVM and MXD in the gastrointestinal target tissues and in H. contortus were higher compared to those measured in plasma. Concentrations of both drugs in H. contortus were correlated with those observed in the abomasal content (r=0.86; p<0.0001). The exposure of H. contortus to IVM and MXD was related to the administered dose. Mean FECRT and efficacy for removal of adult H. contortus was 0% for IVM at 0.2 and 0.4?mg/kg. For MXD, FECRT were >95% for both treatments, and efficacy against H. contortus was 85.1% and 98.1% for 0.2 and 0.4?mg/kg, respectively. The ex vivo accumulation of IVM and MXD in H. contortus was directly related to the drug concentration present in the environment and was influenced by the duration of exposure.

CONCLUSION: Administration of IVM and MXD at 0.4 compared with 0.2?mg/kg accounted for enhanced drug exposure in the target tissues, as well as higher drug concentrations within resistant nematodes. The current work is a further contribution to the evaluation of the relationship between drug efficacy and basic pharmacological issues in the presence of resistant parasite populations.