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1.
Res Vet Sci ; 173: 105271, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38631075

ABSTRACT

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.


Subject(s)
Dog Diseases , Drug Combinations , Macrolides , Pyrantel Pamoate , Animals , Dogs , Macrolides/administration & dosage , Macrolides/therapeutic use , Macrolides/adverse effects , Male , Female , Dog Diseases/drug therapy , Pyrantel Pamoate/administration & dosage , Pyrantel Pamoate/therapeutic use , Pyrantel Pamoate/adverse effects , Isoxazoles/administration & dosage , Isoxazoles/therapeutic use , Administration, Oral , Dirofilariasis/drug therapy , Dirofilaria immitis/drug effects , Naphthalenes/administration & dosage
2.
Medicine (Baltimore) ; 98(27): e16321, 2019 Jul.
Article in English | MEDLINE | ID: mdl-31277177

ABSTRACT

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.


Subject(s)
Antinematodal Agents/adverse effects , Myasthenia Gravis/chemically induced , Pyrantel Pamoate/adverse effects , Administration, Oral , Antinematodal Agents/administration & dosage , Child, Preschool , Female , Humans , Myasthenia Gravis/diagnosis , Myasthenia Gravis/therapy , Pyrantel Pamoate/administration & dosage
3.
Drug Dev Ind Pharm ; 45(2): 222-230, 2019 Feb.
Article in English | MEDLINE | ID: mdl-30260721

ABSTRACT

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.


Subject(s)
Caffeine/chemistry , Calcium Carbonate/chemistry , Pyrantel Pamoate/analogs & derivatives , Administration, Oral , Caffeine/administration & dosage , Drug Compounding , Drug Stability , Microscopy, Electron, Scanning , Pyrantel Pamoate/administration & dosage , Pyrantel Pamoate/chemistry , Saliva/chemistry , Solubility , Suspensions , Tablets
4.
Lancet Infect Dis ; 18(8): 864-873, 2018 08.
Article in English | MEDLINE | ID: mdl-29858149

ABSTRACT

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.


Subject(s)
Albendazole/administration & dosage , Anthelmintics/administration & dosage , Drug Therapy, Combination , Macrolides/administration & dosage , Phenylenediamines/administration & dosage , Pyrantel Pamoate/analogs & derivatives , Trichuriasis/drug therapy , Administration, Oral , Adolescent , Animals , Child , Female , Humans , Male , Mebendazole , Pyrantel Pamoate/administration & dosage , Single-Blind Method , Trichuris/isolation & purification
5.
J Feline Med Surg ; 20(10): 900-904, 2018 10.
Article in English | MEDLINE | ID: mdl-29017390

ABSTRACT

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.


Subject(s)
Anthelmintics/pharmacokinetics , Cats/metabolism , Praziquantel/pharmacokinetics , Pyrantel Pamoate/pharmacokinetics , Administration, Oral , Animals , Anthelmintics/administration & dosage , Area Under Curve , Cats/blood , Drug Combinations , Female , Male , Praziquantel/administration & dosage , Pyrantel Pamoate/administration & dosage , Random Allocation , Treatment Outcome
6.
Int J Parasitol Drugs Drug Resist ; 7(2): 159-173, 2017 08.
Article in English | MEDLINE | ID: mdl-28371660

ABSTRACT

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.


Subject(s)
Albendazole/analogs & derivatives , Anthelmintics/administration & dosage , Mebendazole/administration & dosage , Nematospiroides dubius/drug effects , Pyrantel Pamoate/analogs & derivatives , Trichuris/drug effects , Administration, Oral , Albendazole/administration & dosage , Albendazole/pharmacokinetics , Animals , Anthelmintics/pharmacokinetics , Gastrointestinal Tract/chemistry , Injections, Intraperitoneal , Mebendazole/pharmacokinetics , Mice , Plasma/chemistry , Pyrantel Pamoate/administration & dosage , Pyrantel Pamoate/pharmacokinetics
7.
Parasit Vectors ; 10(1): 52, 2017 01 31.
Article in English | MEDLINE | ID: mdl-28143543

ABSTRACT

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.


Subject(s)
Antiprotozoal Agents/therapeutic use , Dog Diseases/drug therapy , Giardiasis/veterinary , Thiazoles/adverse effects , Thiazoles/therapeutic use , Administration, Oral , Alanine Transaminase/blood , Animals , Antiprotozoal Agents/administration & dosage , Antiprotozoal Agents/adverse effects , Aspartate Aminotransferases/blood , Cryptosporidiosis/drug therapy , Cryptosporidium/drug effects , Dog Diseases/parasitology , Dogs , Feces/parasitology , Giardia/drug effects , Giardia/isolation & purification , Giardia/physiology , Giardiasis/drug therapy , Giardiasis/parasitology , Guanidines/administration & dosage , Guanidines/adverse effects , Guanidines/therapeutic use , Humans , Nitro Compounds , Praziquantel/administration & dosage , Praziquantel/adverse effects , Praziquantel/therapeutic use , Pyrantel Pamoate/administration & dosage , Pyrantel Pamoate/adverse effects , Pyrantel Pamoate/therapeutic use , Thiazoles/administration & dosage
8.
Vet Parasitol ; 229: 73-75, 2016 Oct 15.
Article in English | MEDLINE | ID: mdl-27809982

ABSTRACT

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.


Subject(s)
Anthelmintics/therapeutic use , Drug Resistance , Enterobiasis/veterinary , Enterobius , Horse Diseases/drug therapy , Ivermectin/therapeutic use , Animals , Anthelmintics/administration & dosage , Enterobiasis/drug therapy , Enterobiasis/parasitology , Enterobius/drug effects , Female , Fenbendazole/administration & dosage , Fenbendazole/therapeutic use , France/epidemiology , Horse Diseases/epidemiology , Horse Diseases/parasitology , Horses , Ivermectin/administration & dosage , Ivermectin/pharmacology , Pyrantel Pamoate/administration & dosage , Pyrantel Pamoate/therapeutic use
9.
J Zoo Wildl Med ; 47(1): 256-70, 2016 Mar.
Article in English | MEDLINE | ID: mdl-27010285

ABSTRACT

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.


Subject(s)
DNA Virus Infections/veterinary , Herpesviridae/isolation & purification , Mycoplasma Infections/veterinary , Mycoplasma/isolation & purification , Ranavirus/isolation & purification , Turtles , 2-Aminopurine/administration & dosage , 2-Aminopurine/analogs & derivatives , 2-Aminopurine/therapeutic use , Animals , Animals, Zoo , Anti-Bacterial Agents/administration & dosage , Anti-Bacterial Agents/therapeutic use , Antinematodal Agents/administration & dosage , Antinematodal Agents/therapeutic use , Antiviral Agents/administration & dosage , Antiviral Agents/therapeutic use , Ceftazidime/administration & dosage , Ceftazidime/therapeutic use , DNA Virus Infections/complications , DNA Virus Infections/drug therapy , DNA Virus Infections/virology , Disease Outbreaks/veterinary , Famciclovir , Female , Male , Mycoplasma Infections/complications , Mycoplasma Infections/drug therapy , Pyrantel Pamoate/administration & dosage , Pyrantel Pamoate/therapeutic use
10.
N Engl J Med ; 370(7): 610-20, 2014 Feb 13.
Article in English | MEDLINE | ID: mdl-24521107

ABSTRACT

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.).


Subject(s)
Albendazole/administration & dosage , Antinematodal Agents/administration & dosage , Pyrantel Pamoate/analogs & derivatives , Trichuriasis/drug therapy , Trichuris , Adolescent , Albendazole/adverse effects , Animals , Antinematodal Agents/adverse effects , Ascariasis/drug therapy , Ascaris lumbricoides , Child , Double-Blind Method , Drug Therapy, Combination , Female , Hookworm Infections/drug therapy , Humans , Male , Mebendazole/administration & dosage , Mebendazole/adverse effects , Pyrantel Pamoate/administration & dosage , Pyrantel Pamoate/adverse effects
12.
J Feline Med Surg ; 16(2): 194-7, 2014 Feb.
Article in English | MEDLINE | ID: mdl-24027052

ABSTRACT

Dracunculiasis is rarely reported in cats, yet over the last few years we have identified two cats with filarioid-like spirurid infections. Case 1 was a 9-year-old cat with pituitary-dependent hyperadrenocorticism from New York tate from which four adult dracunculoid nematodes were isolated from its torso. Based on morphometric characteristics and parasite geographic distribution, the specimens were identified as Dracunculus insignis females; at least one of the females was gravid, suggestive of patent infection. Species identification was confirmed through amplification and sequence analysis of nuclear and mitochondrial loci. Case 2 was a 14-year-old diabetic cat from Massachusetts. Formalin-fixed sections were obtained from a subcutaneous mass excised from the left foreleg. Histopathological examination revealed a large nematode with morphometrical characteristics of Dracunculus, surrounded by lymphocytes and sheets of eosinophils. These two cases appear to be the first published reports of dracunculiasis in domestic cats in the USA, and based on the findings from case 1, D insignis may be the species associated with both infections.


Subject(s)
Cat Diseases/parasitology , Dracunculiasis/veterinary , Dracunculus Nematode/isolation & purification , Animals , Cat Diseases/drug therapy , Cat Diseases/epidemiology , Cats , Dracunculiasis/diagnosis , Dracunculiasis/drug therapy , Dracunculiasis/epidemiology , Drug Combinations , Female , Male , New England/epidemiology , Praziquantel/administration & dosage , Praziquantel/therapeutic use , Pyrantel Pamoate/administration & dosage , Pyrantel Pamoate/therapeutic use
13.
PLoS Negl Trop Dis ; 7(3): e2119, 2013.
Article in English | MEDLINE | ID: mdl-23556013

ABSTRACT

BACKGROUND: It is widely recognized that only a handful of drugs are available against soil-transmitted helminthiasis, all of which are characterized by a low efficacy against Trichuris trichiura, when administered as single doses. The re-evaluation of old, forgotten drugs is a promising strategy to identify alternative anthelminthic drug candidates or drug combinations. METHODOLOGY: We studied the activity of the veterinary drug oxantel pamoate against Trichuris muris, Ancylostoma ceylanicum and Necator americanus in vitro and in vivo. In addition, the dose-effect of oxantel pamoate combined with albendazole, mebendazole, levamisole, pyrantel pamoate and ivermectin was studied against T. muris in vitro and additive or synergistic combinations were followed up in vivo. PRINCIPAL FINDINGS: We calculated an ED50 of 4.7 mg/kg for oxantel pamoate against T. muris in mice. Combinations of oxantel pamoate with pyrantel pamoate behaved antagonistically in vitro (combination index (CI) = 2.53). Oxantel pamoate combined with levamisole, albendazole or ivermectin using ratios based on their ED50s revealed antagonistic effects in vivo (CI = 1.27, 1.90 and 1.27, respectively). A highly synergistic effect (CI = 0.15) was observed when oxantel pamoate-mebendazole was administered to T. muris-infected mice. Oxantel pamoate (10 mg/kg) lacked activity against Ancylostoma ceylanicum and Necator americanus in vivo. CONCLUSION/SIGNIFICANCE: Our study confirms the excellent trichuricidal properties of oxantel pamoate. Since the drug lacks activity against hookworms it is necessary to combine oxantel pamoate with a partner drug with anti-hookworm properties. Synergistic effects were observed for oxantel pamoate-mebendazole, hence this combination should be studied in more detail. Since, of the standard drugs, albendazole has the highest efficacy against hookworms, additional investigations on the combination effect of oxantel pamoate-albendazole should be launched.


Subject(s)
Ancylostomiasis/drug therapy , Anthelmintics/administration & dosage , Necatoriasis/drug therapy , Pyrantel Pamoate/analogs & derivatives , Trichuriasis/drug therapy , Ancylostoma/drug effects , Ancylostomiasis/parasitology , Animals , Anthelmintics/pharmacology , Disease Models, Animal , Drug Synergism , Drug Therapy, Combination/methods , Female , Mice , Mice, Inbred C57BL , Necator americanus/drug effects , Necatoriasis/parasitology , Parasitic Sensitivity Tests , Pyrantel Pamoate/administration & dosage , Pyrantel Pamoate/pharmacology , Treatment Outcome , Trichuriasis/parasitology , Trichuris/drug effects
15.
Nihon Shokakibyo Gakkai Zasshi ; 107(5): 768-74, 2010 May.
Article in Japanese | MEDLINE | ID: mdl-20460851

ABSTRACT

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.


Subject(s)
Antinematodal Agents/administration & dosage , Ascariasis/drug therapy , Catheterization/methods , Gallbladder Diseases/drug therapy , Pyrantel Pamoate/administration & dosage , Adult , Ascariasis/diagnostic imaging , Gallbladder , Gallbladder Diseases/diagnostic imaging , Humans , Injections/instrumentation , Liver , Male , Ultrasonography
16.
Vet Parasitol ; 172(1-2): 164-7, 2010 Aug 27.
Article in English | MEDLINE | ID: mdl-20471177

ABSTRACT

A study was carried out to assess the field efficacy of moxidectin (MOX) against Parascaris equorum in foals. A total of 70 foals from 2 Italian thoroughbred (Farms 1 and 2) stud farms and one trotter stud farm (Farm 3), aged 3-5 months and with faecal egg counts (FEC) f>or=300 eggs per gram (EPG) were included in the study. On each farm, foals were divided into 2 groups (of 10, 8 and 10 foals, respectively) and treated with either moxidectin (MOX, 400 mcg/kg b.w.) or ivermectin (IVM, 200 mcg/kg b.w.) on day 0 and examined for faecal count reduction (FECR) on day 14. Five, 4 and 5 foals, respectively, were kept as untreated controls. An individually based estimation of efficacy was assessed by a bootstrap simulation to evaluate the percent reduction of FECRs. Two thousand bootstrap resamples were constructed from individual FECRs and the parasite population was considered susceptible for FECs>or=90% and 95% lower confidence limit (CL)>90%, suspected resistant for FECRs>or=90% and 95% LCL<90% and resistant when FECR<90% and 95% LCL<90%. On day 14, foals with FECRs categorized as resistant or suspected resistant were treated with pyrantel pamoate (PYR, 13.2mg/kg b.w.) and examined for FECR on days 28 and 35. On day 14, MOX and IVM treatments were ineffective in all foals from both thoroughbred farms, while MOX ad IVM were effective (FECRs>90%) in 7 and 5 trotter foals, respectively, and remained >90% until day 35. PYR treatment given on day 14 to remaining 8 foals (3 MOX-treated and 5 IVM-treated) was fully efficacious at faecal examinations carried out on days 28 and 35.


Subject(s)
Anthelmintics/pharmacology , Ascaridida Infections/veterinary , Ascaridoidea/growth & development , Gastrointestinal Diseases/veterinary , Horse Diseases/parasitology , Ivermectin/pharmacology , Pyrantel Pamoate/pharmacology , Animals , Anthelmintics/administration & dosage , Anthelmintics/therapeutic use , Ascaridida Infections/drug therapy , Ascaridida Infections/parasitology , Computer Simulation , Feces/parasitology , Female , Gastrointestinal Diseases/drug therapy , Gastrointestinal Diseases/parasitology , Horse Diseases/drug therapy , Horses , Ivermectin/administration & dosage , Ivermectin/therapeutic use , Male , Parasite Egg Count/veterinary , Pyrantel Pamoate/administration & dosage , Pyrantel Pamoate/therapeutic use , Random Allocation
17.
Vet Parasitol ; 171(1-2): 106-10, 2010 Jul 15.
Article in English | MEDLINE | ID: mdl-20307935

ABSTRACT

In recent years, numerous veterinary practitioners have reported anecdotal episodes in which anthelmintic treatment did not appear to deliver the expected efficacy against equine pinworms (Oxyuris equi). Anthelmintic resistance has not been demonstrated formally in equine pinworms, so a clinical study was designed to evaluate the efficacy of paste formulations of pyrantel pamoate or ivermectin against naturally acquired infections with O. equi. Twenty-one horses (>4 months to 15 years of age) with patent, naturally acquired pinworm infections were blocked by source of origin and allocated randomly to one of three treatment groups: horses (n=7) assigned to Group 1 were treated orally with pyrantel pamoate paste at a dosage of 13.2 mg/kg (2x label dosage), Group 2 horses (n=7) were untreated controls, and horses (n=7) assigned to Group 3 were treated orally with ivermectin paste at a dosage of 200 microg/kg. Fourteen days after treatment, horses were euthanatized, necropsied, and large intestinal contents were processed for recovery of adult pinworms. In addition, duplicate 1% aliquots of intestinal contents from the cecum, ventral colon, dorsal colon, and small colon were collected, preserved, and examined for recovery and enumeration of fourth-stage larval O. equi. Anthelmintic efficacy against pinworms was evaluated by comparing the post-treatment worm counts of Groups 1 and 3 to those of control animals. Mean numbers of O. equi adults recovered postmortem were significantly decreased by both pyrantel pamoate (P=0.0366) and ivermectin (P=0.0137) treatment, with respective efficacies of 91.2% and 96.0%. In addition, both products demonstrated >99% efficacy against fourth-stage O. equi larvae. The current study demonstrated acceptable adulticidal and larvicidal efficacy of both pyrantel pamoate and ivermectin paste formulations against O. equi and did not support the existence of macrocyclic lactone or pyrimidine resistance in the pinworm populations evaluated.


Subject(s)
Anthelmintics/pharmacology , Enterobiasis/veterinary , Enterobius/growth & development , Gastrointestinal Diseases/veterinary , Horse Diseases/parasitology , Ivermectin/pharmacology , Pyrantel Pamoate/pharmacology , Administration, Oral , Animals , Anthelmintics/administration & dosage , Anthelmintics/standards , Anthelmintics/therapeutic use , Enterobiasis/drug therapy , Enterobiasis/parasitology , Feces/parasitology , Gastrointestinal Diseases/drug therapy , Gastrointestinal Diseases/parasitology , Horse Diseases/drug therapy , Horses , Ivermectin/administration & dosage , Ivermectin/standards , Ivermectin/therapeutic use , Least-Squares Analysis , Parasite Egg Count/veterinary , Pyrantel Pamoate/administration & dosage , Pyrantel Pamoate/standards , Pyrantel Pamoate/therapeutic use , Random Allocation , Single-Blind Method
18.
Vet Parasitol ; 171(1-2): 111-5, 2010 Jul 15.
Article in English | MEDLINE | ID: mdl-20307936

ABSTRACT

The expanding prevalence of Parascaris equorum populations that are resistant to macrocyclic lactone (ML) anthelmintics makes it desirable to identify dewormers which remain effective. The objective was to evaluate the efficacy of pyrantel pamoate in 14 suckling foals that had been infected orally with approximately 600 larvated eggs of a P. equorum isolate selected for ML resistance (ML-R). Seventy days after inoculation, foals were weaned, housed individually, and fecal samples were examined frequently to detect the onset of patency. Between 73 and 80 days post-inoculation, all 14 foals developed P. equorum egg counts>or=150 eggs per gram (EPG). An initial cohort of eight foals was treated orally with ivermectin paste (200 microg/kg) 84-91 days post-inoculation. Egg counts were reduced by only 47% at 2 weeks after ivermectin treatment, confirming the ML-R status of the isolate. A second cohort of six foals was not treated with ivermectin. Within each cohort, eligible foals were allocated randomly to treated (pyrantel pamoate; n=7) or untreated control (n=7) groups. Treated foals were dosed orally on Day 0 with a paste formulation of pyrantel pamoate at 13.2mg/kg. Mean ascarid egg counts of treated foals were reduced by 96.0% and 98.8% at 1 and 2 weeks post-treatment, respectively. On Day 14, foals were euthanatized and specimens of P. equorum were recovered from the gut contents, preserved in 10% formalin, and counted. Mean numbers of P. equorum adults recovered postmortem were significantly lower (P=0.0031) in foals treated with pyrantel pamoate (X=1.7; range 0-16) compared to control foals (X=63.0; range 0-320). A paste formulation of pyrantel pamoate, at a dosage of 13.2 mg/kg, was 97.3% effective against a ML-R isolate of P. equorum.


Subject(s)
Anthelmintics/therapeutic use , Ascaridida Infections/veterinary , Ascaridoidea/growth & development , Gastrointestinal Diseases/parasitology , Horse Diseases/parasitology , Pyrantel Pamoate/therapeutic use , Animals , Animals, Suckling , Anthelmintics/administration & dosage , Anthelmintics/standards , Ascaridida Infections/drug therapy , Ascaridida Infections/parasitology , Cohort Studies , Drug Resistance , Feces/parasitology , Female , Gastrointestinal Diseases/drug therapy , Horse Diseases/drug therapy , Horses , Least-Squares Analysis , Male , Parasite Egg Count/veterinary , Pyrantel Pamoate/administration & dosage , Pyrantel Pamoate/standards , Random Allocation
19.
Korean J Parasitol ; 48(4): 339-42, 2010 Dec.
Article in English | MEDLINE | ID: mdl-21234239

ABSTRACT

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.


Subject(s)
Heterophyidae/isolation & purification , Trematode Infections/epidemiology , Trematode Infections/parasitology , Adult , Animals , Antiparasitic Agents/administration & dosage , Feces/parasitology , Female , Heterophyidae/anatomy & histology , Heterophyidae/classification , Humans , Laos/epidemiology , Male , Middle Aged , Praziquantel/administration & dosage , Prevalence , Pyrantel Pamoate/administration & dosage , Trematode Infections/drug therapy
20.
Article in English | WPRIM (Western Pacific) | ID: wpr-62039

ABSTRACT

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.


Subject(s)
Adult , Animals , Female , Humans , Male , Middle Aged , Antiparasitic Agents/administration & dosage , Feces/parasitology , Heterophyidae/anatomy & histology , Laos/epidemiology , Praziquantel/administration & dosage , Prevalence , Pyrantel Pamoate/administration & dosage , Trematode Infections/drug therapy
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