Target animal safety and tolerance study of pyrantel pamoate paste (19.13% w/w pyrantel base) administered orally to horses

Pyrantel pamoate paste (19.13% w/w pyrantel base) for the treatment of tapeworm, Anoplocephala spp was evaluated for target animal safety and tolerance in horses treated orally at 0, 1, 3, 5, and 10 times the clinical dose of 13.2 mg pyrantel base/kg body weight administered daily for six consecutive days. Parameters evaluated included clinical signs, food and water consumption, body weights, physical examinations, clinical pathology (hematology, coagulation, serum chemistry, urinalyses, and fecal examinations), complete necropsy, organ weights, and histopathology. No adverse events or test article-related effects were observed in any treatment group during daily clinical observations of the test animals. Statistically significant changes (P < .05) lacked a dose- and/or time-dependent trend and were considered incidental. Administration of pyrantel pamoate paste did not produce any macroscopic or microscopic tissue effects in any dose group of either sex. The no-observed-effect-level (NOEL) for pyrantel pamoate paste, when administered orally to horses once daily for 6 consecutive days, was determined to be 132 mg/kg/day. Pyrantel pamoate paste (19.13% w/w pyrantel base) can be safely administered orally to horses at 13.2 mg of pyrantel base/kg for the treatment of Anoplocephala infestations.     

Clinical trials of efficacy of praziquantel horse paste 9% against tapeworms and its safety in horses

The aim of this study with horses and a few ponies naturally infected with tapeworms was to confirm in clinical trials the efficacy and safety of a praziquantel horse paste 9%. The field trials were conducted in 1997 and 1998 in Canada, France, Germany and New Zealand. A secondary aim of the study in Canada was to determine if a 24h post-treatment fecal sample provides the best estimate of the prevalence of tapeworms in horses when using a fecal examination technique. Fecal samples were taken from each of 1062 animals at least three times pre-treatment (PRT). In Canada, fecal samples were examined using the Cornell-Wisconsin centrifugal flotation technique, and in France, Germany and New Zealand using a centrifugation/flotation technique. In each trial, the animals were randomized into two treatment groups: praziquantel horse paste 9% at 1mg/kg body weight (BW) and untreated. Fecal samples were taken from each animal nine times post-treatment and over a period of 5 weeks. In Canada, a fecal sample was taken also at 24h after treatment. Personnel examining the samples were "blinded" to treatment groups. On the day of treatment, each treated animal was examined for adverse reactions to the paste 10min after treatment and then hourly for 4h. Thereafter, each animal was examined once daily for 5 weeks. In Canada, Germany and New Zealand, the only tapeworm egg found was Anoplocephala perfoliata. In France, A. perfoliata was the most common species and a few animals had A. magna and Paranoplocephala mamillana. The prevalence of A. perfoliata among animals sampled in Canada, France, Germany and New Zealand was 51.8, 34.4, 13.1 and 26.2%, respectively. A total of 248 animals were treated with the praziquantel paste and all except one accepted it readily. There were 292 animals completing the study, 219 treated and 73 untreated. In Canada, Germany and New Zealand, the efficacy of the praziquantel horse paste 9% against A. perfoliata was 100%. In France, the efficacy against A. perfoliata, A. magna and P. mamillana was 90.9, 100 and 100%, respectively. The best estimate of prevalence for A. perfoliata in a herd was derived from fecal samples taken 24h after treatment. At 24h, 22 of 23 treated horses were positive, whereas on any day pre-treatment fewer horses were positive. Adverse reactions observed were mild to moderate colic and in only two treated horses.     

The efficacy of pyrantel pamoate against ascarids and hookworms in cats

The purposes of this study were to evaluate pyrantel pamoate administered orally at 20 mg/kg body weight for the removal of induced or natural infections of Ancylostoma tubaeformae and Toxocara cati in cats and to compare the efficacy of paste (40 mg base/g) and granule (80 mg base/g) formulations. Thirty cats of mixed breeding and various ages with natural and/or induced infections of A. tubaeformae and T. cati were assigned to one of three treatment groups: (1) non-medicated controls; (2) paste formulation at 20 mg base/kg; or (3) granule formulation at 20 mg base/kg. Infections were induced by feeding the cats on carcasses of infected mice. The study was conducted in replicates of at least one animal per treatment per replicate. The study parameters included clinical observations, physical examinations, faecal egg counts and the numbers, species and stages of worms recovered at necropsy. The paste formulation was 99.3% and 99.7% effective in reducing egg counts of Ancylostoma sp. and Toxocara sp. respectively. The granule formulation was 97.7% and 99.9% effective in reducing faecal egg counts of Ancylostoma sp. and Toxocara sp. respectively. When administered in paste form, pyrantel pamoate was 99.5% effective in removing adult Ancylostoma and 100.0% effective against adult Toxocara. The granule formulation was 97.9% effective against Ancylostoma and 100% effective against Toxocara. No toxic effects of either formulation of the drug were noted.     

Efficacy of Fipronil (9.8% w/w) + (S)-Methoprene (8.8% w/w) and Imidacloprid (8.8% w/w) + Permethrin (44% w/w) against Dermacentor variabilis (American Dog Tick) on Dogs.

This study evaluated overall efficacy, percentage of dogs free of live ticks, retention of ticks, and efficacy against retained ticks of fipronil (9.8% w/w) + (S)-methoprene (8.8% w/w) and imidacloprid (8.8% w/w) + permethrin (44% w/w) spot-on topical solutions against Dermacentor variabilis infesting dogs. Fipronil + (S)-methoprene provided significantly (P less than .05) greater tick control compared with the control dogs for the entire 30-day study period. Conversely, the combination product of imidacloprid + permethrin demonstrated activity significantly (P less than .05) different from control dogs only up to day 23. Significantly (P less than .05) more dogs treated with fipronil + (S)-methoprene were free of live ticks compared with controls on days 3, 9, and 16. There was never a significant difference (P greater than .05) between control and imidacloprid + permethrin-treated dogs in numbers of dogs free of live ticks. After the initial 10-minute tick exposure, lower numbers of ticks were retained on the imidacloprid + permethrin-treated dogs than on the fipronil + (S)-methoprene-treated dogs. However, when evaluating the effectiveness of the acaricides on "retained ticks," it appears that while some of the ticks were rapidly knocked down on the imidacloprid + permethrin-treated dogs, efficacy against ticks still retained at 10 minutes was never greater than 50%.     

Evaluation of the efficacy and safety of two formulations of pyrantel pamoate in cats

The efficacy of paste and granule formulations of pyrantel pamoate against concurrent infections of Toxocara cati and Ancylostoma tubaeforme in cats was examined in a controlled trial. Three groups of 8 cats received either no medication (controls) or pyrantel pamoate in paste or granule formulations at a dosage of 20 mg/kg of body weight. After administration of the paste formulation, fecal egg counts of A tubaeforme and T cati were decreased by 98.6 and 96.4%, respectively, and 100% of hookworms and 93.5% of ascarids were removed from the intestine. After administration of the granule formulation, fecal egg counts of A tubaeforme and T cati were decreased by 99.4 and 78.2%, respectively, and 100% of adult hookworms and 88.9% of ascarids were removed. All reductions of egg counts and worm numbers were significant (P less than 0.01). The clinical safety of pyrantel pamoate was evaluated in 4- to 6-week-old kittens. Three groups of 10 kittens received either no medication (controls) or pyrantel pamoate in paste or granule formulations at the rate of 100 mg/kg for 3 consecutive days. Adverse effects were not observed in young kittens following administration of the high dose of pyrantel pamoate.     

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.     

Anthelmintic efficacy of febantel paste in naturally infected calves

The purpose of the present study was to verify results of the lowest dose (5 mg kg-1) of febantel evaluated in an earlier trial in which there were no differences in efficacies of three dose rates (5, 7.5 and 10 mg kg-1 body weight) against natural gastrointestinal nematode infections of cattle. Fourteen Angus calves (mean weight and age of 155 kg and 525 days, respectively), from the same farm, with relatively heavy (mean of 448 eggs g-1 feces (epg] parasite burdens were selected. After an adjustment period of 8 days in drylot, beginning on 25 July, seven calves were treated with a 45.5% paste formulation of febantel. On Day 7 post-treatment, calves were necropsied for determination of residual worms. Rectal fecal samples were obtained prior to adjustment, at treatment, 5 days post-treatment and at necropsy. On both Day 5 post-treatment and at necropsy a mean of less than 1 epg was recovered from treated calves compared with 765 and 1566 epg, respectively, in control calves. Worms counts at necropsy revealed an efficacy of 98.5% against all adult abomasal worms (Haemonchus placei, 100%, P less than 0.02; Trichostrongylus axei, 99.4%, P less than 0.0001; Ostertagia ostertagi, 90.5%, P less than 0.0002). Treatment was 100% efficacious against adult small and large intestinal worms. However, numbers of Bunostomum phlebotomum, O. radiatum and Trichuris spp. recovered in the control calves were too low to enable a reliable test of drug efficacy. Treatment was not effective against either mucosal or luminal fourth stage larvae of abomasal O. ostertagi.(ABSTRACT TRUNCATED AT 250 WORDS)     

Determination of the efficacy of pyrantel pamoate at the therapeutic dose rate against the tapeworm Anoplocephala perfoliata in equids using a modification of the critical test method

A total of 59 equids (54 horses and five Shetland ponies) were treated with pyrantel pamoate once, at the dose rate of approximately 6.6 mg base kg-1, during the period November 1985-January 1988. The drug was administered as a paste formulation (51 equids) intraorally or as a suspension formulation by stomach tube (eight equids). The purpose of treatment was to evaluate the activity of pyrantel pamoate (at the therapeutic dose rate) for removal of the tapeworm, Anoplocephala perfoliata, by a modified (24-h) critical test. The presence or absence of tapeworms was not determined for the equids before treatment. Twenty-three (39%) of the 59 treated equids were found to be infected with A. perfoliata (from one to 180 specimens per infected equid) at necropsy. Removals varied from 67 to 100% (average 88%) for the 18 infected equids treated with the paste formulation. For the five infected equids treated with the suspension, removals were 58-100% (average 75%). The combined average removal of A. perfoliata for both formulations was 87%. Two abnormal (triradiate) specimens of A. perfoliata were recovered; one from each of two different equids.     

Comparison of efficacy and safety of paste formulations of firocoxib and phenylbutazone in horses with naturally occurring osteoarthritis

OBJECTIVE: To compare efficacy and safety of paste formulations of firocoxib and phenylbutazone in horses with naturally occurring osteoarthritis. DESIGN: Randomized controlled clinical trial. ANIMALS: 253 client-owned horses with naturally occurring osteoarthritis. PROCEDURES: Horses were treated with firocoxib (0.1 mg/kg [0.045 mg/lb], PO, q 24 h) or phenylbutazone (4.4 mg/kg [2 mg/lb], PO, q 24 h) for 14 days. Physical examinations and lameness evaluations were performed prior to treatment and after 7 and 14 days. Clinical improvement was defined as a reduction of at least 1 lameness grade or a combined reduction of at least 3 points in scores for pain during manipulation or palpation, joint swelling, joint circumference, and range of motion. RESULTS: Proportion of horses clinically improved on day 14 for the firocoxib group (104/123 [84.6%]) was not significantly different from the proportion for the phenylbutazone group (103/119 [86.6%]). Proportion of horses that were improved on day 14 was significantly greater for horses treated with firocoxib than for horses treated with phenylbutazone with regard to score for pain on manipulation or palpation (P = 0.028), joint circumference score (P = 0.026), and range of motion score (P = 0.012), but not for overall lameness score or joint swelling score. No direct treatment-related adverse effects were detected during the study. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested that overall clinical efficacy of a paste formulation of firocoxib in horses with naturally occurring osteoarthritis was comparable to efficacy of a paste formulation of phenylbutazone.     

A study to evaluate the field efficacy of ivermectin, fenbendazole and pyrantel pamoate, with preliminary observations on the efficacy of doramectin, as anthelmintics in horses

The efficacy of ivermectin, fenbendazole, pyrantel pamoate and doramectin was evaluated under field conditions at 2 sites in the Free State Province of South Africa. The study involved 25 horses at each site, divided into 5 groups of equal size. Ivermectin, fenbendazole and pyrantel pamoate were administered orally at doses of 0.2, 10 and 19 mg/kg respectively. Doramectin was administered by intramuscular injection at a dose of 0.2 mg/kg. Treatment efficacy was based on the mean faecal egg count reduction 14 days post treatment. At site A a faecal egg count reduction of 100% was found after treatment with ivermectin, fenbendazole and doramectin. A 96.1% reduction was found after treatment with pyrantel pamoate. At site B ivermectin and doramectin produced a 100% reduction in faecal egg counts, fenbendazole produced an 80.8% reduction and pyrantel pamoate a 94.1% reduction. Doramectin produced a 100% reduction in faecal egg counts at both sites, despite not being registered for use in horses. In addition, the results indicated reduced efficacy of fenbendazole at site B, which suggested benzimidazole resistance. Larval cultures showed that cyathostomes accounted for between 86 and 96% of pre-treatment parasite burdens at both sites. Other helminths identified in the faecal samples were Strongylus spp. and Trichostrongylus axei.     

Evaluation of an imidacloprid (8.8% w/w)--permethrin (44.0% w/w) topical spot-on and a fipronil (9.8% w/w)--(S)-methoprene (8.8% w/w) topical spot-on to repel, prevent attachment, and kill adult Ixodes scapularis and Amblyomma americanum ticks on dogs

This study evaluated the effectiveness of two topical spot-on formulations -- imidacloprid(8.8% w/w)-permethrin (44.0% w/w) and fipronil (9.8% w/w)-(S)-methoprene (8.8% w/w)--to repel, prevent the attachment of, and kill adult Ixodes scapularis and Amblyomma americanum on dogs. Twelve purpose-bred beagles were distributed into three groups of four dogs each; one group served as untreated controls, and each of the other two groups received one of the test products. Dogs were exposed to 25 adult ticks of each species for 10 minutes on posttreatment days 3, 7, 14, 21, and 28. Unattached or repelled ticks were collected and evaluated for viability, and on-dog tick counts were conducted at 3, 24, and 48 hours after tick exposure. The imidacloprid-permethrin formulation provided significant repellency against I. scapularis for up to 3 weeks after treatment, and both formulations provided good overall control of I. scapularis and A. americanum during the study period.     

Evaluation of an imidacloprid (8.8% w/w)--permethrin (44.0% w/w) topical spot-on and a fipronil (9.8% w/w)--(S)-methoprene (8.8% w/w) topical spot-on to repel, prevent attachment, and kill adult Rhipicephalus sanguineus and Dermacentor variabilis ticks on dogs

This study evaluated the effectiveness of two topical spot-on formulations, imidacloprid (8.8% w/w)--permethrin (44.0% w/w) and fipronil (9.8% w/w)--(S)-methoprene (8.8% w/w), to repel, prevent the attachment of, and kill adult Rhipicephalus sanguineus and Dermacentor variabilis on dogs. Twelve purpose-bred beagles were distributed into three groups of four dogs each; one group served as untreated controls and each of the other two groups received one of the test products. Dogs were exposed to 25 adult ticks of each species for 10 minutes on posttreatment days 3, 7, 14, 21, and 28. Nonattached or repelled ticks were collected and evaluated for viability, and on-dog tick counts were conducted at 3, 24, and 48 hours after tick exposure. The imidacloprid-permethrin formulation provided significant repellency of R. sanguineus and D. variabilis for up to 3 and 4 weeks after treatment, respectively; and provided good overall control for R. sanguineus and D. variabilis during the study period. The fipronil--(S)-methoprene formulation provided good overall tick control during the study period.     

Efficacy of imidacloprid (8.8% w/w) plus permethrin (44% w/w) spot-on topical solution against Amblyomma americanum infesting dogs using a natural tick exposure model

This study evaluated the efficacy of an imidacloprid 8.8% w/w + permethrin 44% w/w spot-on topical solution (K9 Advantix, Bayer Animal Health) against Amblyomma americanum using a natural field exposure model. Sixteen beagles were divided into two groups of eight dogs each. One group of dogs was treated with K9 Advantix and the other group served as untreated controls. On day -1 and at 3, 7, 14, 21 and 28 days after treatment, the dogs were walked for 80 minutes in an A. americanum-infested habitat at the Konza Prairie Biological Station in Northeastern Kansas. Postexposure tick counts (efficacy evaluations) were conducted on each dog at 3 and 48 hours after exposure. At 3 days after treatment, the efficacy of K9 Advantix within 3 hours of natural tick exposure was 88.0% and declined slowly during the study. The 48-hour postexposure efficacy remained above 93.5% throughout the study.     

A study on the seasonal epidemiology of Anoplocephala spp.-infection in horses and the appropriate treatment using a praziquantel gel (Droncit 9% oral gel)

In a study on the seasonal dynamics of the gastro-intestinal nematode egg production in horses, one breeding farm also revealed a particularly high prevalence of Anoplocephala spp. infection. Consequently, this farm was chosen for analysing the seasonal pattern of the tapeworm egg excretion over a one year period in order to establish the most favourable periods for an appropriate and successful cestocidal treatment. The seasonal analysis showed a significantly higher (p < 0.05) Anoplocephala spp. egg excretion between July and October, i.e. during the second part of the grazing period. This result clearly underlines the importance of a cestocidal treatment during that period of the year. Subsequently, horses of this farm and of a second farm with a high prevalence of Anoplocephala spp. were used to evaluate the efficacy of praziquantel in a specific oral gel formulation for horses under field conditions. The efficacy of praziquantel was tested in a total of 33 horses from the two farms harbouring a coproscopically detected Anoplocephala spp. infection prior to treatment. Praziquantel (Droncit 9%, oral gel, 1 mg/kg bodyweight) was administered to the horses according to their body weight. The efficacy of the drug was evaluated ten days after treatment by a double faecal analysis. Thereby, no Anoplocephala spp. eggs were found in the faeces of 32 horses (97%). The single horse remaining positive for Anoplocephala spp. eggs did not completely swallow the anthelmintic gel and consequently, did not receive the appropriate dose of the drug.     

Comparison of ivermectin, oxibendazole, and pyrantel pamoate in suppressing fecal egg output in horses

Thirty resident horses at a boarding stable in Alberta were used to evaluate the relative efficacies of ivermectin, oxibendazole, and pyrantel pamoate in reducing fecal egg output in adult horses under routine management conditions during spring and early summer, and to more clearly define the duration of suppression of fecal egg production following anthelmintic treatment. Horses were blocked according to pretreatment egg counts and randomly assigned to one of three treatments: pyrantel pamoate at 6.6 mg/kg body weight; oxibendazole at 10 mg/kg body weight; or ivermectin at 200 μg/kg body weight. All treatments were administered orally as a paste on day 0.Fecal samples were collected for examination by the modified Wisconsin procedure before treatment, and then at 4-11 day intervals up to day 72.

Very few if any strongyle eggs were found in the feces of any horses up to day 35. On days 42, 50 and 57, the geometric mean egg count for the ivermectin group was significantly (p<0.05) lower than that for the oxibendazole or pyrantel pamoate groups. Based on a survival curve analysis of the data, the mean number of days for recurrence of eggs in the feces was significantly longer for the ivermectin group than for the oxibendazole and pyrantel pamoate groups.

Under conditions encountered in this study, the posttreatment interval to resumption of fecal egg out-put in horses treated with ivermectin was eight to nine weeks, compared with five to six weeks for horses treated with oxibendazole or pyrantel pamoate.

     

Field efficacy of ivermectin plus praziquantel oral paste against naturally acquired gastrointestinal nematodes and cestodes of horses in North America and Europe

The efficacy of an oral formulation of ivermectin plus praziquantel in the reduction of nematode and cestode egg counts in horses was assessed in 273 horses under field conditions at 15 sites in North America (n = 6) and Europe (n = 9). Horses were confirmed by fecal examination to have natural infections of strongyles (100%) and tapeworms (76%). Replicates of four horses were formed at each site, and in each replicate three animals received ivermectin (0.2 mg/kg body weight) plus praziquantel (1 mg/kg body weight) oral paste and one animal remained untreated or received vehicle paste. Fecal samples were collected for fecal nematode and cestode egg counting before and 7, 8, 9, 14, 15, and 16 days after treatment. Horses treated with ivermectin plus praziquantel oral paste had significantly (P <.01) lower posttreatment strongylid and cestode egg counts (reductions of 98% or more) than controls. Combined site analyses revealed that 95% or 96% of the horses positive for cestode eggs before treatment that were treated with ivermectin plus praziquantel were negative for cestode eggs at each posttreatment fecal examination. No adverse reactions attributable to ivermectin plus praziquantel oral paste treatments were observed. The results of the studies demonstrated that ivermectin plus praziquantel paste was highly effective in reducing egg shedding by gastrointestinal nematodes and cestodes, and no adverse reactions were observed in horses treated under field conditions.