Clinical field efficacy and safety of pyrantel pamoate paste (19.13% w/w pyrantel base) against Anoplocephala spp. in naturally infected horses

Clinical field trials were conducted at five geographical locations in the USA (Oklahoma, Wisconsin, Tennessee, Virginia and Idaho) to evaluate the efficacy and safety of pyrantel pamoate paste (19.13%, w/w, pyrantel base) administered at the recommended dosage of 13.2 mg pyrantel base/kg (6.0 mg pyrantel base/lb) body weight (b.w.) against tapeworm infections of Anoplocephala spp. in naturally infected horses. Horses at each study site were allocated by restricted randomization based on the cestode status (positive or negative) of pre-treatment fecal egg counts to complete sets of four animals each or incomplete sets of fewer than four animals. Within sets comprising of two to four horses, one animal was randomly allocated to receive placebo vehicle paste and the remaining horse(s) received pyrantel pamoate paste administered orally at a minimum dosage of 13.2 mg pyrantel base/kg b.w. on Test Day (TD) 0. Single animal sets received pyrantel pamoate paste. Fecal samples of horses were collected and examined for equine tapeworm (Anoplocephala spp.) eggs a minimum of four times (once or thrice between TD -28 and -14, twice between TD -14 and -7, and once on TD 0) prior to treatment on TD 0. Fecal samples of horses that were positive for cestode infection pre-treatment were examined for cestode eggs on TD 7, 8, 9, 14, 15 and 16. Cestode-negative pre-treatment horses were not sampled again after treatment. A total of 241 horses (141 mares, 16 stallions and 84 geldings; 6 months-30 yrs of age; 173-646 kg; 13 recognized breeds and various crossbreds) were evaluated. The prevalence of Anoplocephala spp. determined by pre-treatment fecal examination ranged from 38.3% in Idaho to 68.1% in Tennessee with an overall prevalence of 52.3%. Ninety cestode-positive and 88 cestode-negative horses were treated with pyrantel pamoate paste, 36 cestode-positive and 27 cestode-negative horses were treated with placebo vehicle paste. Overall, 178 horses were treated with pyrantel pamoate paste, and 63 horses were treated with placebo paste. Of the 178 horses treated with pyrantel pamoate paste, no drug related, adverse clinical or neurological health events were observed. No doses of pyrantel pamoate paste were refused or lost during dosing. At each post-treatment time sampling interval, significantly fewer cestode eggs (P < 0.0115) were passed by cestode-positive horses treated with pyrantel pamoate paste compared to cestode-positive horses that received placebo paste. Efficacy of the pyrantel pamoate paste treatment ranged from 92 to 96% from TD 7 to TD 16 with an overall efficacy of 95%. The results of these trials demonstrated that pyrantel pamoate paste (19.13%, w/w, pyrantel base) administered orally at a dosage of 13.2 mg pyrantel base/kg b.w. is highly efficacious (95%) against Anoplocephala spp. and safe for use in horses with no adverse clinical or neurological health events observed under field use conditions.     

Dose-confirmation studies of the cestocidal activity of pyrantel pamoate paste in horses

Dose confirmation studies of the cestocidal activity of pyrantel pamoate paste were conducted at two sites in North America during 2001. Horses with naturally-acquired cestode infections were identified by detection of typical Anoplocephala spp. eggs in feces collected between 7 and 92 days prior to treatment. Twenty and 22 horses were enrolled at Site 1 (Urbana, IL) and Site 2 (Knoxville, TN), respectively. Candidate horses were acclimated to study conditions for 14 days, ranked by length of interval since coprologic confirmation, and allocated randomly to one of two treatment groups: (T1) pyrantel pamoate paste 13.2mg pyrantel base per kilogram body weight administered orally, and (T2) untreated controls. Individual doses of pyrantel pamoate paste were prepared on the basis of contemporaneous body weights and administered to Group T1 horses on Day 0. Trained personnel monitored the animals at regular intervals after treatment to detect potential adverse reactions. Horses were euthanatized and necropsied 10-12 days after treatment. The contents of the large and small intestines were collected, and the walls of each organ were rinsed with water and inspected. Attached cestodes were recovered and preserved in 10% formalin. The intestinal contents and rinsed ingesta were washed over a #10-mesh (2mm aperture) sieve and tapeworms were extracted and preserved. Recovered cestodes were counted and examined at 1-4x magnification for identification to genus and species. At Site 1, specimens of Anoplocephala perfoliata were recovered from seven of 10 control horses, and from one of 10 horses treated with pyrantel pamoate. Mean cestode numbers were 4.52 in the control group and 0.07 for treated horses. At Site 2, cestodes were found in 10 of 11 controls (mean 26.2) and in five of 11 horses (mean 1.2) treated with pyrantel pamoate. In both studies, Group T1 means were significantly lower than the control group (P<0.005). The calculated efficacies were 98.4 and 95.5% at Sites 1 and 2, respectively. In two dose-confirmation studies, a single, oral treatment of pyrantel pamoate paste (19.13% w/w pyrantel base) at 13.2mg/kg was >or=95.5% effective against A. perfoliata in naturally-infected horses.     

Prevalence and Treatment of Tapeworms in Horses

A study was initiated to determine the prevalence of tapeworms in horses in Southern Ontario and to investigate the efficacy of pyrantel pamoate, niclosamide and mebendazole. Fecal samples were taken from 580 horses of various breeds, ages and sexes in 24 locations and Anoplocephala perfoliata was found in 13.6%. This was regarded as a minimum, the true rate being probably significantly higher and the reasons for this are discussed. A brief review of the life cycle and effects of tapeworms in horses and a comparison of two flotation techniques for the diagnosis of A. perfoliata eggs in feces is given.Pyrantel pamoate, niclosamide and mebendazole were compared for efficacy in field and critical trials. In field trials, pyrantel base and niclosamide at 6.6 and 50 mg/kg respectively were found to be effective, but in critical trials their efficacy was poor, 15 and 5.6% respectively. These anthelmintics at these dose rates caused only an elimination of the terminal egg bearing segments and were without significant effect on the entire tapeworm. When pyrantel base was administered at 13.2 and 19.8 mg/kg (twice and three times the therapeutic dose rate for nematodes respectively) the efficacy was 97.8 and 100%. It would appear that pyrantel pamoate administered at 13.2 mg pyrantel base/kg is an effective therapeutic dose for tapeworms in horses. Further dose titration studies are needed for niclosamide. Mebendazole was without effect at up to four (35.2 mg/kg) times the therapeutic dose for nematodes.     

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.

     

Efficacy of fenbendazole granules and pyrantel pamoate suspension against Toxocara canis in greyhounds housed in contaminated runs.

The efficacy of fenbendazole granules against Toxocara canis in naturally infected greyhounds housed in contaminated environments was evaluated. Eight pens, each containing three to seven greyhounds, 3-12 months of age, were randomly allotted into two treatment groups. Greyhounds in Group 1 were treated with fenbendazole granules mixed in their feed at 50 mg/kg/day for 3 consecutive days once a month for 4 months. Greyhounds in Group 2 were treated with pyrantel pamoate suspension at 5.0 mg/kg per os once a month for 4 months. Quantitative fecal examinations were performed on days 0, 10 and then on the first day of each monthly treatment. Greyhounds administered fenbendazole had fecal egg count reductions (FECRs) of 95.8 and 99.8% at 10 and 31 days following initial treatment, respectively. Greyhounds administered pyrantel pamoate had FECRs of 85.8 and 88.3% at 10 and 31 days after the first treatment, respectively. T. canis fecal egg counts conducted from Day 31 through Day 128 were significant lower in those greyhounds administered fenbendazole as compared to greyhounds administered pyrantel pamoate. Fenbendazole produced FECRs in greyhounds from Day 31 through Day 128 by 96.8-99.8%. Pyrantel pamoate reduced fecal egg counts during the same time period 71.4-98.3%.     

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.     

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.     

Evidence of Ivermectin Resistance by Parascaris equorum on a Texas Horse Farm

By collecting fecal samples every 2 weeks beginning at 2 months of age, 32 foals from a single Texas farm were monitored. The foals were administered ivermectin paste at the time of the first collection and again monthly. When foals had Parascaris egg counts higher 2 weeks after ivermectin treatment than at treatment, they were administered pyrantel pamoate at the manufacturer's recommended dose (6.6 mg/kg) or at twice the recommended dose (13.2 mg/ kg) when tapeworm eggs were also detected. An elevation or only minimal reduction (less than 75%) in Parascaris egg counts was seen 2 weeks after ivermectin treatment until the foals were 8 months of age, at which time there was an 85% reduction in fecal egg count after treatment. When pyrantel was administered at the manufacturer's recommended dose, a 42% to 84% reduction in egg counts occurred, but at 13.2 mg/kg there was a 98% to 100% reduction in fecal egg counts 2 weeks posttreatment. However, pyrantel failed to control strongylate egg counts even at the elevated dose, whereas ivermectin reduced strongylate fecal egg counts by greater than 99%, determined 2 weeks posttreatment. Pyrantel, but not ivermectin, lowered Parascaris egg counts. Ivermectin, but not pyrantel, lowered strongyle egg counts 2 weeks post administration. A single drug for all ages of horses approach to parasite control requires rethinking. Combinations of drugs or more careful evaluation of anthelmintics in foals may be necessary for continued parasite control.     

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.     

A comparison of two programs (pyrantel tartrate administered daily and 3X pyrantel pamoate adminitered at 8-week intervals) for the reduction of tapeworm EPG in the horse

A 26-week study was conducted with 24 horses to compare the effectiveness of two different treatment regimens in reducing the number of tapeworm eggs per gram (EPG) of feces. Ten horses were treated daily with 2.6 mg/kg of pyrantel tartrate (approved normal dosage for nematodes). Eleven horses received pyrantel pamoate at 8-week intervals at 19.8 mg/kg (3X the normal use for nematodes). Three horses served as controls and received ivermectin at 8-week intervals. Levels of tapeworm EPG were monitored at 2-week intervals for the duration of the 26-week period of study. Prior to administration of the first treatment, all 24 horses had positive EPG counts. Following the second week of treatment, no tapeworm eggs were detected in fecal samples of the 10 horses treated with pyrantel tartrate. Of the 11 horses treated with 3X pyrantel pamoate at 8-week intervals, one to two at each sample collection date had positive tapeworm EPG counts through the tenth week following the initial treatment, that is, through two weeks following the second 3X pyrantel pamoate treatment. Of the three control horses treated only with invermectin, at least one, and sometimes all three, had positive EPG counts at each collection date, indicating continuous tapeworm infection.     

Pyrantel pamoate resistance in horses receiving daily administration of pyrantel tartrate

CASE DESCRIPTIONS: 16 horses treated daily with pyrantel tartrate (2.64 mg/kg [1.2 mg/lb], PO) as part of a prophylactic anthelmintic program. CLINICAL FINDINGS: Fecal worm egg counts (FWECs) were obtained on all 16 horses. Mean FWEC was 478 eggs/g (epg; range, 0 to 4,075 epg). Three of the 16 horses were responsible for 85% of the total fecal egg output for the herd on the day of sampling. Six horses had FWECs < 200 epg. Three horses that had arrived within 4 months of the sampling date had FWECs < 100 epg. TREATMENT AND OUTCOME: An FWEC reduction test was initiated the day after FWECs were obtained; all horses with FWECs > 100 epg (9 horses) were treated with pyrantel pamoate (6.6 mg/kg [3 mg/lb], PO), and 14 days later, the FWEC was repeated. During the 14-day period, all horses received pyrantel tartrate (2.64 mg/kg, PO) daily. Fecal worm egg count reduction was calculated for each horse. Mean FWEC reduction for the group was 28.5% (range, increase of 21% in FWECs 14 days after treatment to a decrease of 100% in FWEC 14 days after treatment). CLINICAL RELEVANCE: Farms should be monitored for cyathostomes resistant to pyrantel pamoate prior to use of pyrantel tartrate. Fecal worm egg counts should be monitored routinely in horses before and after treatment to ensure efficacy of cyathostome control measures.     

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.     

Anthelmintic treatment in horses: the extra-label use of products and the danger of under-dosing

Anthelmintic products form the basis of helminth control practices on horse stud farms at present. Regular evaluation of the efficacy of these products is advisable, as it will provide information on the worm egg reappearance period and the resistance status in the worm population. The aim of this study was to evaluate the efficacy of doramectin, pyrantel pamoate, ivermectin and moxidectin on a Thoroughbred stud farm in the Western Cape Province, South Africa. The study also compared the anthelmintic efficacy of two moxidectin formulations administered at their recommended dosages (an injectable, at 0.2 mg/kg, not registered for horses, and an oral gel at 0.4 mg/kg, registered for horses). Two mixed-sex groups of 30 yearlings and 40 weaners were tested in 2001 and 2002, respectively, divided into 3 and 4 groups of equal size. In 2001, moxidectin was one of 3 drugs administered orally and at a dose rate of 0.4 mg/kg. In 2002, pyrantel pamoate and ivermectin were orally administered at 19 and 0.2 mg/kg. Moxidectin and doramectin (the latter not registered for horses) were administered by intramuscular injection at a dose of 0.2 mg/kg, the dosage registered for other host species. The faecal egg count reduction test was used to determine the anthelmintic efficacies in both years. Each animal acted as its own control and the arithmetic mean faecal egg count and lower 95% confidence limit was calculated for each of the groups. A 100% reduction in the faecal egg counts and a 100% lower 95% confidence limit was recorded for moxidectin (0.4 mg/kg) in 2001. In 2002, a 99% and 96% reduction was recorded for pyrantel pamoate and ivermectin, respectively. In the same year doramectin and moxidectin (both injectable and given at 0.2 mg/kg) did not have any effect on worm egg counts. Of the 4 drugs tested in 2002, only pyrantel pamoate recorded lower 95% confidence limits above 90%.     

Comparison of anthelmintic activity of pyrantel, praziquantel, and nitazoxanide against Anoplocephala perfoliata in Horses

Three anthelmintics were compared for efficacy in reducing the egg production of Anoplocephala perfoliata in a herd of central Texas horses. Two trials were run, 1 in mares and the other in weanlings that were diagnosed as being infected with Anoplocephala by recovery of eggs in 5 g of feces with sugar centrifugation. Each animal was evaluated twice before treatment and again twice following treatment (at weeks 2 and 4 after treatment). The criteria for infection were the recovery of eggs on at least 1 occasion before treatment and the finding of eggs on 1 day following treatment. The mares were treated 1 time with either pyrantel pamoate at 13.2 mg/kg, nitazoxanide at 100 mg/kg, praziquantel at 1.23 mg/kg or remained as untreated controls. The weanlings were treated with pyrantel at 13.7 mg/kg nitazoxanide at 100 mg/kg or remained as untreated controls. The percentage reduction of patient infection in mares after treatment with pyrantel was 83%, with nitazoxanide was 78%, and with praziquantel was 83% and in controls was 17%. There was a 75% reduction of patient weanlings treated with pyrantel or nitazoxanide and a 17% reduction in untreated controls. The reduction of infection in all horses treated with any drug was significantly different from controls. All of the drugs were somewhat effective in the control of Anoplocephala, and there were no differences among the drugs in their effectiveness.

Introduction

Anoplocephala perfoliata, the lappeted tapeworm, is an inhabitant of the intestine of equids. Adult tapeworms attach to the intestinal mucosa at the ileocaecal valve and, when present in large numbers, cause edema and hypertrophy of the ileum. The disease manifest by this infection may be inapparent or may give rise to colic (abdominal pain) in the horse apparently from mechanical obstruction or intussusception of the small intestine into the caecocolon.^{1, 2, 3, 4, 5, 6, 7 and 8} The prevalence of infection is geographically variable^{9, 10, 11, 12 and 13} but appears to be increasing,¹⁴ with a much higher rate of infection found with necropsy as opposed to fecal observations. Horses become infected by the ingestion of infected orbatid mites in pastures. Orbatid mites, the intermediate hosts, are predatory and are found in decaying organic material, such as leaf litter. Horses of all ages are infected, but there are lower numbers of clinical cases in horses older than 4 years of age.⁴ The intensity of infection is highest in the late summer and autumn.^{8 and 12} Anthelmintics with reported efficacy against A perfoliata include pyrantel pamoate at 13.2 mg/kg,¹⁰ pyrantel tartrate at 2.6 mg/kg for 30 days,¹⁵ pyrantel embonate at 38 mg/kg,¹⁶ and praziquantel at 1 to 2 mg/kg.^{17 and 18} Nitazoxanide has not been evaluated for Anoplocephala but was included in the trial because of its effects against nematodes and tapeworms in humans.¹⁹ Because Anoplocephala infections may cause disease and there is a perception that current anthelmintics may not be as effective as in the past, a study was done to compare anthelmintics to lower the intensity of fecal egg counts in a herd of horses in central Texas.

Materials and methods

Quarter horse mares and weanlings from a single herd were evaluated with 5 g of feces with a sucrose double centrifugation test to determine whether eggs of Anoplocephala were present.²⁰ Feces from each individual horse were evaluated twice, once approximately 2 weeks before treatment and again on the day of treatment. If Anoplocephala eggs were found on either date, the horse was considered to have positive results. Within each group (mares or weanlings), the treatment selection was randomly allocated as the horses were restrained for treatment. Fecal samples were again evaluated at 14 and 28 days after treatment for the presence or absence of eggs on either day.The dose for each individual horse was determined by chest girth weight tape at the time of treatment. The treatments were as follows: pyrantel pamoate (Strongid-T, Pfizer Animal Health, Exton, Pa) at 13.7 mg/kg via nasogastric intubation (12 mares, 8 weanlings), nitazoxanide oral paste (Nitazoxanide, Idexx Laboratories, Westbrook, Me) at 100 mg/kg (9 mares, 8 weanlings), praziquantel (Droncet injectable, Bayer Corp, Shawnee Mission, Kan) at 1.23 mg/kg via nasogastric intubation (6 mares), and untreated controls (6 mares, 6 weanlings). A 1-tailed Fisher exact test was used to compare rates of infection before and after treatment. If a mare or foal did not have positive results before treatment, it was not evaluated in this study.

Results and discussion

No abnormal clinical signs were seen after treatment with any of the products. Treatment was administered to several additional animals with each product, but they were not included in the analysis if they did not have positive results on 1 of the 2 evaluations before treatment, hence, the different numbers of horses in treatment groups.None of the horses in the trial exhibited clinical signs associated with the infection of A perfoliata. However, before the trial, a mare from the infected herd exhibited signs of colic and Anoplocephala eggs were detected in the feces. Examination of the remainder of the herd gave impetus to the study.Mean egg counts before and after treatment are given in the Table.The presence of strongylate and Parascaris eggs in weanlings served as a control of the methodology of evaluation. The difficulty of finding Anoplocephala eggs has been recognized by several authors,^{5, 8, 13, 14 and 21} but the authors also recognize that when there were greater numbers of parasites there was increased egg production. Therefore, finding of eggs with fecal flotation indicated that there were 20 worms or more. However, there appears to be no correlation between the number of worms and egg counts once the detection threshold is reached,²² so the criterion for evaluation was the presence of eggs in the feces before treatment compared with after treatment. Although mean egg counts were not compared, the number of eggs in each infected horse was less after treatment in all groups compared with untreated controls (Table). The method of evaluation used in this study cannot be equated to those of critical^{10 and 16} or control¹⁴ studies in which horses are killed so that all worms are detected. However, the use of clinical studies to compare compounds is useful in detecting which anthelmintics are likely to be of value against geographically distinct populations of worms. Admittedly, more sampling may have increased the number of horses with positive results, both before and after treatment.     

A modified critical test for the efficacy of pyrantel pamoate for Anoplocephala perfoliata in equids

Aims of this study with 13 equids naturally infected with Anoplocephala perfoliata were to document (i) a critical test with a period of 48 h from treatment to necropsy to assess the efficacy of an anthelmintic against the tapeworm, (ii) the efficacy of pyrantel pamoate oral paste at 13.2 mg pyrantel base/kg body weight, and (iii) the time after treatment when fecal egg counts would best estimate the tapeworm's prevalence in a herd. Feces passed in successive 12-h periods after treatment were examined for tapeworms. At necropsy, tapeworms in equids were identified as attached to the mucosa or unattached and, with a stereoscope, as normal or abnormal. At the time of treatment and at 6-h intervals thereafter, fecal samples were taken for egg counts. The efficacy of pyrantel pamoate was 96.6%; in 1 equid the efficacy was 75.3%, and in 8 it was 100%. "Major fragments" (worms without a scolex) accounted for 10% of the tapeworms recovered; they were not included in the efficacy analysis but should be. In 3 untreated equids necropsied, tapeworms were in the cecum, and 21.3% were detached. This protocol, when compared with a 24-h one without examination of feces, was more efficient in the treatment of trial animals and reduced underestimation and overestimation of an anthelmintic's efficacy. However, a protocol similar to this 48-h critical test but with a 24- or 36-h post-treatment period should be investigated. The mean egg count peaked 18 to 24 h after treatment and the samples taken at that time would provide the best estimate of prevelance of tapeworms in a herd. The Cornell-Wisconsin centrifugal flotation technique had a sensitivity and specificity of 100% at 18 h and 92% and 100%, respectively, at 24 h.     

Safety study of a beef-based chewable tablet formulation of ivermectin and pyrantel pamoate in growing dogs, pups, and breeding adult dogs.

To determine the safety of a new combination of ivermectin and pyrantel (as pamoate salt) in a novel beef-based chewable tablet formulation, 3 tolerance trials were conducted and included growing dogs, pups, and breeding adult dogs. Growing dogs, given the combination orally for 5 consecutive days at recommended dosages (5 mg of pyrantel/kg of body weight, 6 micrograms of ivermectin/kg) or at twice the pyrantel dosage in combination with the recommended dosage of ivermectin, had no adverse effects. The combination also was administered to 6-week-old pups at 1, 3, and 5 times the recommended dose on 3 successive days for 3 times in 1 month. Compared with age-matched controls, treatment had no effect on clinical status, growth rate, or gross or histologic features. Breeding male and female dogs given the combination at 3 times the recommended dose for extended periods had no adverse effects, and prevalence of abnormalities in the offspring was not greater than that in nonmedicated controls.     

Evaluation of a beef-based chewable formulation of pyrantel pamoate against induced and natural infections of hookworms and ascarids in dogs.

Pyrantel pamoate, formulated in a beef-based chewable tablet, was evaluated for efficacy in dogs against induced and natural infections of Toxocara canis, Toxascaris leonina, Ancylostoma caninum and Uncinaria stenocephala. Dose titration trials were conducted in Canada, the UK and Germany in dogs treated with pyrantel (as pamoate salt) at 0, 2.5, 5 or 10 mg kg-1 body weight. These studies showed that a dose rate of 2.5 mg kg-1, the efficacy of pyrantel against adult T. canis, T. leonina, U. stenocephala and A. caninum was 76.1, 85.6, 100 and 87.9%, respectively. Efficacy at 5 mg kg-1 against the same parasites was 94.2, 92.0, 93.5 and 93.8%, respectively, and at 10 mg kg-1 efficacy was 91.2, 97.6, 98.7 and 91.3%, respectively. No adverse effects due to treatment were seen in any of these trials.     

The disposition of pyrantel in the gastrointestinal tract and effect of digesta flow rate on the kinetic behaviour of pyrantel in the pig

Pigs consuming a diet with slow digesta transit time were orally administered with molar equivalent doses of pyrantel as the citrate and pamoate salt. At appropriate intervals pigs were killed and the quantitative-time distribution of pyrantel throughout the gut contents was determined. Compared with the citrate, there appeared to be greater quantities of the less soluble pamoate salt in the small and large intestine. An additional group of pigs fed on diets with "slow" or "fast" digesta transit time were orally treated with molar equivalent amounts of pyrantel as the citrate and pamoate salt and the respective kinetic disposition of pyrantel in peripheral plasma and quantitative excretion in faeces was determined. The diet type had little effect on pyrantel availability after administration of the less soluble pamoate salt. However, the maximum concentration of pyrantel in plasma was lower and there appeared to be greater quantities of pyrantel retained in the gut and excreted in faeces when the citrate salt was orally administered to pigs fed the "fast" compared to the "slow" diet. Since it is the quantity of pyrantel contained in the gut lumen which is believed to affect efficacy against gastrointestinal parasites, greater efficacy with this anthelmintic should be obtained when pigs are consuming a high fibre diet.     

Comparison of the efficacy of ivermectin, oxibendazole, and pyrantel pamoate against 28-day Parascaris equorum larvae in the intestine of pony foals

Sixteen helminth-free pony foals were inoculated with a mean (+/- SD) 2,000 (+/- 545.5) infective Parascaris equorum eggs (day 0). Foals were allocated to replicates of 4, and treatments within each replicate were assigned at random. Treatment administered on postinoculation day (PID) 28 included no treatment (control), 0.2 mg of ivermectin/kg of body weight, 10 mg of oxibendazole/kg, or 6.6 mg of pyrantel base (pamoate)/kg. Paste formulations of the anthelmintics were administered orally. The foals were euthanatized 14 days after treatment (PID 42) and examined for P equorum larvae in the small intestine. The mean +/- SD (and range) numbers of fourth-stage P equorum larvae recovered from nontreated foals and those treated with ivermectin, pyrantel, or oxibendazole were 1,603.8 +/- 1,026.8 (305 to 2,480), 29.3 +/- 55.8 (0 to 113), 413.0 +/- 568.1 (0 to 1,204), or 889.5 +/- 1,123.1 (1 to 2,345), respectively. Compared with the value for control (nontreated) foals, treatment with ivermectin, pyrantel, and oxibendazole was 98.2, 74.2, and 44.5% effective, respectively, when administered 28 days after experimentally induced infection with P equorum. Adverse reactions attributable to treatment were not observed.     

Activity of selected antioxidative enzymes in rats exposed to dimethoate and pyrantel tartrate

This study presents the results of research concerning the effect of single and combined application of pyrantel tartrate and dimethoate on selected antioxidative enzymes: catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GPx), in rat erythrocytes. Pyrantel tartrate was applied twice, at a dose of 85 mg/kg bw at a two week interval, i.e. on day 14 and 28 of the experiment, orally, in a water solution with a stomach tube. Dimethoate was administered with drinking water for 28 days at a dose of 25 mg/kg bw/day. It was found that pyrantel tartrate caused only small changes in the activity of the antioxidative enzymes under analysis. Subchronic exposure of rats to dimethoate caused a significant increase in the activity of CAT, SOD and GPx in erythrocytes, indicating the existence of strong oxidative stress. In combined intoxication, no significant effects of administering pyrantel tartrate on the activity of CAT, SOD and GPx was found in animals poisoned with dimethoate. The profile of changes was similar to that observed in rats exposed only to the organophosphorus insecticide. This may indicate a lack of interaction between the compounds used in the experiment.