Stability investigation of FCC-based tablets for oral suspension with caffeine and oxantel pamoate as model drugs.

Tablets for oral suspension (TOS) present a convenient alternative dosage form to conventional tablets. Dispersed in a glass of water or on a spoon, such tablets can be easily administered, which can become beneficial for pediatric or geriatric patients. The novel excipient functionalized calcium carbonate (FCC), consisting of calcium carbonate and calcium phosphate, has already shown to be suitable to produce orally disintegrating placebo tablets. In this study, the influence of formulation composition on disintegration time in water and artificial saliva was investigated using caffeine and oxantel pamoate as model drugs, reflecting BCS class 1 and BCS class 4, respectively. The optimized formulation for each model drug underwent a stress test. The results show that the drug content in DTs was not influenced by FCC under stressed conditions, however the disintegration and dissolution performance was affected by temperature and humidity. It can be concluded that it was possible to produce TOS characterized by rapid disintegration complemented by high physical stability of the tablets and chemical stability of the drug.

Oxantel pamoate-albendazole for Trichuris trichiura infection.

BACKGROUND: Infections with soil-transmitted helminths (Ascaris lumbricoides, hookworm, and Trichuris trichiura) are widespread and often occur concomitantly. These parasitic-worm infections are typically treated with albendazole or mebendazole, but both drugs show low efficacy against T. trichiura. Albendazole is the drug of choice against hookworm. METHODS: In this double-blind trial conducted on Pemba Island, Tanzania, we randomly assigned children, 6 to 14 years of age, to receive one of four treatments: oxantel pamoate at a dose of 20 mg per kilogram of body weight, plus 400 mg of albendazole, administered on consecutive days; oxantel pamoate at a single dose of 20 mg per kilogram; albendazole at a single dose of 400 mg; or mebendazole at a single dose of 500 mg. We assessed the efficacy and safety profile of oxantel pamoate-albendazole when used in the treatment of T. trichiura infection (primary outcome) and concomitant soil-transmitted helminth infection (secondary outcome). Efficacy was determined by means of assessment of the cure rate and egg-reduction rate. Adverse events were assessed four times after treatment. RESULTS: Complete data were available for 458 children, of whom 450 were infected with T. trichiura, 443 with hookworm, and 293 with A. lumbricoides. The cure rate of T. trichiura infection was significantly higher with oxantel pamoate-albendazole than with mebendazole (31.2% vs. 11.8%, P=0.001), as was the egg-reduction rate (96.0% [95% confidence interval {CI}, 93.5 to 97.6] vs. 75.0% [95% CI, 64.2 to 82.0]). The cure rate with albendazole (2.6%) and the egg-reduction rate with albendazole (45.0%; 95% CI, 32.0 to 56.4) were significantly lower than the rates with mebendazole (P=0.02 for the comparison of cure rates). Oxantel pamoate had low efficacy against hookworm and A. lumbricoides. Adverse events (mainly mild) were reported by 30.9% of all children. CONCLUSIONS: Treatment with oxantel pamoate-albendazole resulted in higher cure and egg-reduction rates for T. trichiura infection than the rates with standard therapy. (Funded by the Medicor Foundation and the Swiss National Science Foundation; Current Controlled Trials number, ISRCTN54577342.).

RANAVIRUS EPIZOOTIC IN CAPTIVE EASTERN BOX TURTLES (TERRAPENE CAROLINA CAROLINA) WITH CONCURRENT HERPESVIRUS AND MYCOPLASMA INFECTION: MANAGEMENT AND MONITORING.

Frog virus 3 (FV3) and FV3-like viruses are members of the genus Ranavirus (family Iridoviridae) and are becoming recognized as significant pathogens of eastern box turtles (Terrapene carolina carolina) in North America. In July 2011, 5 turtles from a group of 27 in Maryland, USA, presented dead or lethargic with what was later diagnosed as fibrinonecrotic stomatitis and cloacitis. The presence of FV3-like virus and herpesvirus was detected by polymerase chain reaction (PCR) in the tested index cases. The remaining 22 animals were isolated, segregated by severity of clinical signs, and treated with nutritional support, fluid therapy, ambient temperature management, antibiotics, and antiviral therapy. Oral swabs were tested serially for FV3-like virus by quantitative real-time PCR (qPCR) and tested at day 0 for herpesvirus and Mycoplasma sp. by conventional PCR. With oral swabs, 77% of the 22 turtles were FV3-like virus positive; however, qPCR on tissues taken during necropsy revealed the true prevalence was 86%. FV3-like virus prevalence and the median number of viral copies being shed significantly declined during the outbreak. The prevalence of herpesvirus and Mycoplasma sp. by PCR of oral swabs at day 0 was 55% and 68%, respectively. The 58% survival rate was higher than previously reported in captive eastern box turtles for a ranavirus epizootic. All surviving turtles brumated normally and emerged the following year with no clinical signs during subsequent monitoring. The immediate initiation of treatment and intensive supportive care were considered the most important contributing factors to the successful outcome in this outbreak.

Safety of an oral combination of moxidectin, afoxolaner, and pyrantel pamoate in dogs.

NexGard®PLUS (moxidectin, afoxolaner, and pyrantel pamoate), is an oral combination product for dogs indicated for the prevention of heartworm disease, the treatment and prevention of flea and tick infestations, and the treatment of gastro-intestinal nematode infections. The safety of this product in dogs was evaluated in three studies. Study #1 was a margin-of-safety study conducted in puppies, dosed six times at 28-day intervals at 1X, 3X, or 5X multiples of the maximum exposure dose (equivalent to 24 µg/kg moxidectin, 5 mg/kg afoxolaner, and 10 mg/kg pyrantel). In Study #2, the product was administered to ABCB1-deficient collie dogs at a 1X dose twice at a 28-day interval, and at a 3X or 5X dose once. Study #3 evaluated the safety of the product at 1X and 3X doses administered three times at 4-week intervals, to dogs harboring adult Dirofilaria immitis. In the three studies, the safety was evaluated on the basis of multiple clinical observations and physical examinations, including a complete assessment of toxicity to macrocyclic lactones, and on comprehensive clinical and anatomical pathology evaluations in Study #1. No clinically significant combination product-related effects were observed in any of the three studies. No signs of macrocyclic lactone toxicity were observed in the ABCB1-deficient collie dogs. Some mild and self-resolving instances of emesis or diarrhea were occasionally observed in the 3X and 5X dosed dogs. NexGard® PLUS was demonstrated to be safe following multiple administrations in puppies, in ABCB1-deficient collie dogs, and in microfilaremic dogs infected with adult D. immitis.

Prevalence of the intestinal flukes Haplorchis taichui and H. yokogawai in a mountainous area of Phongsaly Province, Lao PDR.

Phongsaly Province, located in the northernmost area of Lao PDR, was previously suggested to be endemic for the liver fluke Opisthorchis viverrini infection. To confirm, or rule out, this suggestion, the Phonxay village in the Khoua District, Phongsaly Province, was selected for a survey. Ten volunteers (8 men and 2 women aged 31-57 years) who consumed raw freshwater fish and had gastrointestinal troubles were treated with a single dose of praziquantel (40 mg/kg) and pyrantel pamoate (10 mg/kg) and purged with magnesium sulfate to recover any worm parasites. Eight of the 10 volunteers expelled 1 or more species of trematodes, nematodes, or cestodes (worm positive rate; 80%). The worms were morphologically identified as H. taichui (861 worms from 8 people), H. yokogawai (59 from 6 people), Phaneropsolus bonnei (1 from 1 person), Trichostrongylus sp. (2 from 2 people), Ascaris lumbricoides (2 from 1 person), Enterobius vermicularis (11 from 3 people), and Taenia saginata (1 strobila with scolex from 1 person). The results indicate that the mountainous area of Phongsaly Province, Lao PDR, is not endemic for the liver fluke but endemic for intestinal flukes, in particular, Haplorchis taichui and H. yokogawai.

[A case of ascariasis in the gallbladder successfully treated with an anthelmintic injection into the gallbladder via a percutaneous transhepatic catheter].

A man in his 40s who had made frequent visits abroad was admitted to our hospital complaining of epigastric pain. Ultrasonography (US) revealed an "inner tube sign" in the gallbladder, which suggested a diagnosis of ascariasis in the gallbladder. Pyrantel pamoate was directly injected into the gallbladder via a percutaneous transhepatic catheter. The worm was dead 10 minutes after the injection. US revealed reduction of the worm's length and then the disappearance of the worm from the gallbladder at both 13 days and 2 months after the injection. This method is less invasive than operation and therefore is possibly more safe. It is known that the number of cases of ascariasis may increase in Japan due to increased organic vegetable consumption and foreign travel. We need to consider this disease in the differential diagnosis of epigastric pain.

Treatment of naturally occurring, asymptomatic Giardia sp. in dogs with Drontal Plus flavour tablets.

The administration of three consecutive daily doses of the recommended 1x dose of Drontal Plus flavour tablets (Bayer) was examined for its effect on Giardia sp. cyst-shedding in 7 treated and 7 untreated random-source dogs. Dogs were treated on study days 0, 1 and 2. Cysts were quantified using direct immunofluorescent labelling on days -7, -5, -3 and -2, and daily from day 1 through 11. Three treated dogs never shed cysts again during the study, one shed again only on day 4, and the remaining three dogs started to shed again on days 8, 9 and 11. The mean numbers of cysts per gramme in the faeces of the treated dogs were significantly reduced (t-tests using log(10)(counts)) on days 1 and 2 (geometric means: controls = 447,000; treated = 1,050; p = 0.004) and days 3 to 8 (geometric means: controls = 23,400; treated 5.0; p < 0.001). Four controls that had been consistently positive, changed to negative status on day 11, and thus, on the final day of the trial, there were only three positive control and three positive treated dogs. Three consecutive days of treatment with Drontal Plus flavour tablets halted Giardia sp. cyst shedding by dogs. But starting six days post third treatment, some of the dogs started shedding cysts again. Since the prepatent period of Giardia sp. can be as short as 4 days, shedding of Giardia sp. cysts 6 days after treatment could be caused by a reinfection.

Synergistic effect of febantel and pyrantel embonate in elimination of Giardia in a gerbil model.

The objectives of the study were to determine the optimal dose of febantel, pyrantel embonate and a combination of febantel/pyrantel embonate required to effectively treat Giardia in a gerbil model and to determine if there is a synergistic effect with the two drugs. SPF gerbils were infected by oral inoculation with 105 Giardia duodenalis trophozoites (day 0). On days 5 to 7, animals (n = 6) were treated once daily via oral gavage with febantel, pyrantel embonate, febantel and pyrantel embonate, metronidazole or placebo. Gerbils were euthanised 24 hours after last treatment and duodenal trophozoites were enumerated on a haemocytometer to obtain a concentration of trophozoites/ cm of gut. Febantel alone, effectively eliminated Giardia trophozoites at 160 and 80 mg/kg. Pyrantel embonate did not eliminate Giardia from the animals but significantly reduced parasite counts at all dosages. Febantel combined with pyrantel embonate effectively eliminated Giardia trophozoites at 160, 80 and 40 mg/kg. Metronidazole did not eliminate Giardia trophozoites from the gut. All placebo-treated animals were heavily infected with Giardia trophozoites. It can be concluded that febantel is more effective in elimination of Giardia infections when combined with pyrantel embonate compared to the agents used alone.

An ocular myasthenia gravis attack after oral pyrantel pamoate: An unusual case report.

RATIONALE: Myasthenia gravis (MG) is an autoimmune disease of the neuromuscular junction that can be triggered by anticholinergic agents. PATIENT CONCERNS: We present a 4-year-old female patient who was admitted to the outpatient clinic. She complained of drooped eyelids, which first appeared 2 days after taking a 200 mg dose of pyrantel pamoate. Past medical history is negative. DIAGNOSES AND TREATMENT: She was hospitalized with a diagnosis of ocular type MG, and pyridostigmine (40 mg/day) treatment was started. OUTCOMES: The patient recovered, and subsequently, the treatment dose was tapered. CONCLUSION: Pyrantel is an antihelminthic that acts as an agonist of nicotinic acetylcholine receptors (AChRs) of nematodes and exerts its therapeutic effects by depolarizing their muscle membranes. Consequently, there may be an association between pyrantel pamoate and MG.

Pharmacokinetics of praziquantel and pyrantel pamoate combination following oral administration in cats.

Objectives The pharmacokinetics of praziquantel and pyrantel pamoate has never been reported in cats. The present study was designed to establish the plasma concentration-time profile and to derive pharmacokinetic data for a combined formulation of praziquantel and pyrantel in cats, after a single, oral administration. Methods Twenty-two clinically healthy adult cats were used, each receiving a single oral dose of praziquantel (8.5 mg/kg) and pyrantel (100 mg/kg). Blood samples were collected at regular time points up to 48 h post-dosing. Plasma concentrations of praziquantel and pyrantel were measured using a liquid chromatography-mass spectrometry-high-throughput screening method. Results Clinical examination of all cats did not reveal any side effects after oral administration of these medications. The terminal half-life for praziquantel and pyrantel was 1.07 and 1.36 h, respectively. Praziquantel peak concentration (Cmax) was 1140 µg/ml, reached at 1.22 h. The plasma concentrations of pyrantel after oral administration were low with a mean Cmax of 0.11 µg/ml, reached at a Tmax of 1.91 h. Pyrantel showed a very limited absorption as pamoate salt, suggesting permanence and efficacy inside the gastrointestinal tract, where the adult stages of most parasitic nematodes reside. Conclusions and relevance Pyrantel showed a very limited absorption as pamoate salt. Praziquantel was rapidly absorbed following oral administration and the concentrations achieved suggest that praziquantel could be an effective and safe medication in cats. Although some resistance problems are arising as a result of their long use, these anthelminthic products can still play a major role in parasitic control, especially in geographical areas where the high cost of newer treatments or necessity of parenteral administration could decrease the number of treated animals.

Efficacy and tolerability of moxidectin alone and in co-administration with albendazole and tribendimidine versus albendazole plus oxantel pamoate against Trichuris trichiura infections: a randomised, non-inferiority, single-blind trial.

BACKGROUND: The recommended anthelmintics show low efficacy in a single-dose regimen against Trichuris trichiura. Moxidectin, a new treatment for river blindness, might complement the drug armamentarium for the treatment and control of soil-transmitted helminthiasis. However, its efficacy against T trichiura has not yet been studied. The aim of the study was to assess the efficacy of moxidectin alone and in co-administrations against T trichiura infection. METHODS: A randomised, single-blind, non-inferiority trial was done in two primary schools and one secondary school in Pemba, Tanzania. Adolescents aged 12-18 years who tested positive for T trichiura were randomly assigned (5:5:3:3) with a computer-generated sequence to receive moxidectin (8 mg) plus albendazole (400 mg), albendazole (400 mg) plus oxantel pamoate (25 mg/kg; reference treatment), moxidectin (8 mg) plus tribendimidine (200 mg or 400 mg), or moxidectin (8 mg) alone. Study group assignments were masked from participants and laboratory technicians. The primary outcome was non-inferiority with a 2 percentage point margin for egg reduction rate (ERR) against T trichiura assessed as the relative change in the geometric mean egg counts from baseline to 14-21 days after treatment with the Kato-Katz method, based on the available case population. Cure rates (CR) and tolerability (assessed 3, 24, and 48 h post treatment) were secondary outcomes. The study is registered at ISRCTN (number 20398469) and is closed to accrual. FINDINGS: 701 students were enrolled between April 1, and Aug 7, 2017. Primary outcome data were available for 634 students. We observed ERRs of 98·5% for moxidectin plus albendazole and 99·8% for albendazole plus oxantel pamoate, resulting in an absolute difference of -1·2 percentage points (95% CI -1·8 to -0·8), meeting the non-inferiority margin. 100 (51%) of 197 students receiving moxidectin plus albendazole and 166 (83%) of 200 receiving albendazole plus oxantel pamoate were cured, indicating a difference of 32 percentage points (odds ratio 5·3, 95% CI 3·3 to 8·7). ERRs were 91·6% for moxidectin-tribendimidine and 83·2% for moxidectin. Only mild adverse events (mainly headache and stomach pain) were reported. The largest number of adverse events (126 [20%] of 632 students) was observed 24 h post treatment, with no difference among the individual treatment arms (ranging from 23 [19%] of 118 students treated with moxidectin to 38 [19%] of 199 with moxidectin plus albendazole). INTERPRETATION: Moxidectin plus albendazole showed non-inferiority to albendazole plus oxantel pamoate in terms of ERR; however, albendazole plus oxantel pamoate showed a considerably higher cure rate. Dose-optimisation studies with moxidectin and moxidectin plus albendazole should be considered since the efficacy of the dose used for the treatment of onchocerciasis (8 mg) in this study might not be optimal for the treatment of T trichiura infections. FUNDING: Thrasher Foundation.

Field evaluation of the efficacy and the safety of a combination of oxantel/pyrantel/praziquantel in the treatment of naturally acquired gastrointestinal nematode and/or cestode infestations in dogs in Europe.

In five multicentre field trials, the efficacy and safety of a combination of oxantel/pyrantel/praziquantel (Dolpac), Vetoquinol SA) in the treatment of naturally acquired gastrointestinal nematode and/or cestode infestation in dogs was evaluated in northern and southern Europe. Forty-eight investigators from France, Belgium, Germany, Italy and Spain enrolled 329 dogs to be treated with the tested combination; 235 of these dogs complied with the inclusion criteria of the protocol and had a tested helminth identified on Day 0. A pooled analysis was performed on each of the following helminth species: Toxocara canis, Ancylostoma caninum, Toxascaris leonina, Trichuris vulpis, Uncinaria stenocephala, Taenia spp. and Dipylidium caninum, which were isolated on Day 0. The main efficacy criterion was the egg per gram (epg) percent reduction of the nematodes and the absence of proglottids and or eggs for the cestodes. After treatment, dogs were examined on Day 7, Day 14 and Day 21. The efficacy of the combination against Toxocara canis was 99.1%, 98.8% and 98.9% on Day 7, Day 14 and Day 21, respectively. At the same occasions the efficacy was, respectively, 99.2%, 99.2% and 99.3% against Ancylostoma caninum, 97.3%, 97.2% and 98.4% against Trichuris vulpis, 98.4%, 98.8% and 98.8% against Uncinaria stenocephala, 98.9%, 99.5% and 99.9% against Toxascaris leonina, 97.1%, 100% and 100% against Dipylidium caninum and 100% against Taenia spp.

Comparison of various anthelmintic therapies for the treatment of Trypanoxyuris microon infection in owl monkeys (Aotus nancymae).

Trypanoxyuris microon is a pinworm that infects New World nonhuman primates, including Aotus nancymae. Although it typically is clinically insignificant, infection may serve as a significant variable during experimental data analysis. In this study we sought to determine the most effective anthelmintic therapy for eradication of T. microon infection in A. nancymae. Animals confirmed to be infected with T. microon by perianal tape test were treated twice (on days 0 and 14) with pyrantel pamoate, ivermectin, or thiabendazole and evaluated for eggs by daily perianal tape test throughout the entire 28-d period. Successful clearance of eggs was defined as 5 consecutive negative perianal tape tests. Pyrantel pamoate and ivermectin were significantly more effective at egg clearance than were thiabendazole and no treatment. Overall, 100% of the pyrantel pamoate and ivermectin treatment groups were cleared of infection after 2 treatments, whereas only 60% of the thiabendazole group became negative for pinworm eggs. In addition, the time after treatment until clearance was 1 to 2 d for pyrantel pamoate, 2 to 4 d for thiabendazole, and 4 to 6.5 d for ivermectin. These results indicate that pyrantel pamoate was the most effective and rapidly acting anthelmintic for the treatment of adult T. microon infection, with ivermectin as a suitable alternative. However because of the potential for continued development of immature stages or reinfection, anthelmintic doses should be repeated after 1 to 2 wk, in combination with effective environmental sanitation.

Exposure of Heligmosomoides polygyrus and Trichuris muris to albendazole, albendazole sulfoxide, mebendazole and oxantel pamoate in vitro and in vivo to elucidate the pathway of drug entry into these gastrointestinal nematodes.

Millions of people are treated with anthelmintics to control soil-transmitted helminth infections; yet, drug distribution in the plasma and gastrointestinal tract compartments and the pathway of drug uptake into gastrointestinal nematodes responsible for the pharmacological effect are unknown. We assessed the distribution and uptake of albendazole, albendazole sulfoxide, albendazole sulfone in the hookworm Heligmosomoides polygyrus in vitro and in vivo as well as the distribution and uptake of albendazole, mebendazole, and oxantel pamoate in the whipworm Trichuris muris in vitro and in vivo. Oral and intraperitoneal treatments (100 mg/kg) were studied. Drug quantities in helminths and host compartments (stomach, the contents and mucosa of the small and large intestine, and the plasma) were determined using HPLC-UV/vis and anthelmintic activities were recorded using phenotypic readout. The influence of 1-aminobenzotriazole (ABT), an irreversible and unspecific cytochrome P450 inhibitor, on albendazole disposition in mice harboring H. polygyrus was evaluated. In vivo, albendazole was found in quantities up to 10 nmol per ten H. polygyrus and up to 31 nmol per ten T. muris. ABT did not change the levels of albendazole or its metabolites in the plasma of mice harboring H. polygyrus or in H. polygyrus, whereas drug levels in the gastrointestinal tract of host mice doubled. Mebendazole and oxantel pamoate quantities per ten T. muris were as high as 21 nmol and 34 nmol, respectively. Albendazole revealed a very dynamic distribution and high rate of metabolism, hence, H. polygyrus and T. muris are exposed to albendazole and both metabolites via multiple pathways. Diffusion through the cuticle seems to be the crucial pathway of oxantel pamoate uptake into T. muris, and likely also for mebendazole. No relationship between concentrations measured in helminths and concentrations in plasma, intestinal content and mucosa of mice, or drug efficacy was noted for any of the drugs studied.

Efficacy of nitazoxanide to treat natural Giardia infections in dogs.

BACKGROUND: Giardia parasites cause gastrointestinal disease in humans, dogs, and many other animals worldwide. The treatment of dogs for giardiasis requires further investigation to ascertain levels of drug efficacy and the possibility of adverse side effects. Nitazoxanide (NTZ) has shown good clinical anti-Giardia activity in humans, yet it has not been evaluated for the treatment of giardiasis in dogs. METHODS: Thirty-five dogs, naturally infected with Giardia were divided into five groups (n = 7): dogs in group NTZ1, NTZ2, and NTZ3 were treated with a single oral dose of 37.5 mg/kg, 75 mg/kg, and 150 mg/kg, respectively, of NTZ on days 0 and 14. The fourth group was treated with a commercially available regimen that includes a combination of pyrantel, praziquantel, and febantel (FEB) administered orally for three consecutive days. Additionally, an untreated control group was established. Giardia cysts from the stool of each dog were quantified on days -3, 0, 5, 7, 9, 11, 14, 18, 25, and 28. Biochemical parameters were evaluated in all dogs, before the first treatment and after concluding the experiment. RESULTS: Shedding of Giardia cysts was reduced in all treated groups when compared to untreated controls (P < 0.01). However, NTZ2, NTZ3, and FEB had a lower risk during the study. Furthermore, NTZ was also effective against another protozoan, Cryptosporidium spp. at doses of 75 mg/kg and 150 mg/kg, in contrast to the combination of febantel + pyrantel + praziquantel. Biochemical parameters of treated animals, namely, aspartate transaminase and alanine transaminase enzymes, remained within physiological ranges. CONCLUSIONS: Based on these results, the implementation of NTZ as a treatment for giardiasis in dogs is proposed. The administration of a single dose is an important advantage of NTZ because it reduces workload, particularly in animals placed in shelters and kennels, where handling of large numbers of animals is required, and personnel is frequently scarce.

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.

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.

Ivermectin failure in the control of Oxyuris equi in a herd of ponies in France.

Drug resistance in equine gastro-intestinal parasitic nematodes has been reported throughout the world. While the focus is usually put on cyathostomins, observations of macrocylic lactone failure against Oxyuris equi have accumulated over the last decade. Here we report the failure of ivermectin in the control of O. equi in an experimental Welsh pony herd. In a first trial, 6 ponies previously drenched with moxidectin and showing patent O. equi infections were administered ivermectin and subsequently monitored for O. equi egg excretion over one month. This trial demonstrated a failure of ivermectin to control O. equi egg excretion as half of ponies demonstrated recurrent egg excretion in the peri-anal region during 21days after treatment. One year later, six female Welsh ponies drenched with moxidectin demonstrated signs of itching and scratching in their peri-anal region with worms being found transiently in fecal materials three weeks later. Ponies were allocated to three treatment groups, i.e. ivermectin, pyrantel embonate and fenbendazole and monitored for egg excretion over five weeks. Fenbendazole and pyrantel embonate broke ivermectin suboptimal efficacy as soon as 8 and 14days respectively after treatment, while egg excretion remained constant throughout the 41-day long trial in the ivermectin-treated ponies. This is the first report of ivermectin failure against O. equi in France. In the absence of critical efficacy test, it remains unclear whether true resistance is at stake or if these observations confound a constitutive suboptimal efficacy of ivermectin against O. equi.

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.