Efficacy of Bravecto® Plus spot-on solution for cats (280 mg/ml fluralaner and 14 mg/ml moxidectin) in the prevention of feline Aelurostrongylus abstrusus infection evaluated in a multi-diagnostic approach.

BACKGROUND: Aelurostrongylus abstrusus is one of the most important respiratory nematodes of felines. Infections may lead to respiratory clinical signs with varying severity or even death, emphasizing the need for preventive treatment of cats with outdoor access to circumvent patent infections. METHODS: Therefore, the preventive efficacy of a spot-on formulation of 280 mg/ml fluralaner and 14 mg/ml moxidectin (Bravecto® Plus spot-on solution for cats, MSD) against A. abstrusus was evaluated in a negative controlled, randomized and partially blinded efficacy study with 28 purpose-bred cats in a non-terminal design. In three different treatment regimes, the minimum recommended dose of 40 mg fluralaner and 2.0 mg moxidectin/kg bodyweight (BW) was administered once at 12, 8 or 4 weeks (study group G1, G2 and G3, respectively) prior to experimental infection with 300 third-stage A. abstrusus larvae, while G4 served as placebo-treated control. RESULTS: From 30 to 46 days post infection (dpi; SD 114 to 130), faeces were sampled to monitor first-stage larvae (L1) excretion for efficacy determination. Secondary efficacy criteria, including respiratory parameters, serological antibody levels and computed tomography (CT) findings, were assessed once before enrolment (SD -7 to -1) and before infection (SD 75 to 83). After infection, CT evaluation was performed once at 47-50 dpi (SD 131 to 134), and respiratory parameters and antibody levels were regularly assessed twice or once a week, respectively (1 up to 78 dpi, SD 85 up to 162). All animals in the control group excreted L1 by 33-37 dpi and remained positive throughout the study period from 41 to 46 dpi (SD 125 to 130). In the treatment groups, only one animal each of G1 and G2 excreted L1 at two consecutive days, and four cats of G1, two of G2 and three of G3 were positive on single occasions. While the geometric mean (GM) of the maximum number of excreted L1 per 5 g of faeces was 7380.89 in the control group (G4), GMs were significantly lower in the treatment groups with 1.63 in G1, 1.37 in G2 and 0.79 in G3. Thus, based on GMs, the reduction in excreted L1 exceeded 99.9% in all three treatment groups. Based on CT severity scores, all lungs of the animals of the control group showed severe pulmonary changes post infection, whereas lungs of the cats of the treatment groups were either unaltered (4 animals), mildly (11 animals), or moderately altered (5 animals). Moreover, seroconversion was observed in all cats of the control group, but not in those of the treatment groups. CONCLUSIONS: The combination of diagnostic methods used in this non-terminal study yielded coherent and reliable results. A single administration of Bravecto® Plus spot-on solution for cats was well tolerated and effective in the prevention of aelurostrongylosis for at least 12 weeks.

Efficacy of Bravecto® Plus spot-on solution for cats (280 mg/ml fluralaner and 14 mg/ml moxidectin) for the prevention of aelurostrongylosis in experimentally infected cats.

BACKGROUND: The feline lungworm Aelurostrongylus abstrusus affects the lower respiratory tract in cats worldwide. As infections may lead to chronic respiratory changes or even death, preventive treatment in cats with outdoor access is warranted. METHODS: The preventive efficacy of a spot-on solution (Bravecto® Plus spot-on solution for cats, MSD) against cat aelurostrongylosis was evaluated using three different preventive treatment regimes in a negative controlled, randomized and partially blinded laboratory efficacy study with 31 purposed-bred cats. The minimum recommended dose of 2.0 mg moxidectin + 40 mg fluralaner/kg bodyweight was applied once 12 (Group [G]1), 8 (G2) or 4 (G3) weeks before experimental infection with 300 third-stage larvae (L3) of A. abstrusus. Another group served as untreated control (G4). Individual faecal samples were analysed as of day 30 post infection (pi) to monitor larvae excretion. Necropsy was performed at days 47-50 pi. The lungs were examined macroscopically for pathological findings and (pre-)adult worms were counted to assess preventive efficacy. RESULTS: Beginning at day 32-40 pi, all cats of the control group were constantly shedding larvae of A. abstrusus, whereas only one animal of G1 excreted larvae at several consecutive days. In addition, two cats of G1 and G3 and three of G2 were positive on a single occasion. The geometric mean (GM) of the maximum number of excreted larvae was 7574.29 in the control group compared to 1.10 (G1), 1.19 (G2) and 0.53 (G3), resulting in a GM reduction of > 99.9% in all treatment groups. All lungs of the control animals showed severe or very severe alterations at necropsy, while in 94.44% of the treated cats lung pathology was rated as absent or mild. The GM number of (pre-)adult A. abstrusus retrieved from the lungs was 26.57 in the control group, 0.09 in G1 and 0.00 in G2 and G3. Thus, GM worm count reduction was 99.66% in G1 and 100% in G2 and G3. CONCLUSIONS: A single application of Bravecto® Plus spot-on solution at a dose of 2.0 mg moxidectin + 40 mg fluralaner/kg bodyweight reliably prevents cat aelurostrongylosis for at least 12 weeks.

Efficacy of imidacloprid 10%/moxidectin 1% spot-on formulation (Advocate®) in the prevention and treatment of feline aelurostrongylosis.

BACKGROUND: In three randomized, controlled laboratory efficacy studies, the efficacy in the prevention of patent infections of a topical combination of imidacloprid 10%/moxidectin 1% (Advocate® spot-on formulation for cats, Bayer Animal Health GmbH) against larval stages and immature adults of Aelurostrongylus abstrusus, as well as the treatment efficacy of a single or three monthly treatments against adult A. abstrusus, were evaluated. METHODS: Cats were experimentally inoculated with 300-800 third-stage larvae (L3). Each group comprised 8 animals and the treatment dose was 10 mg/kg bodyweight (bw) imidacloprid and 1 mg/kg bw moxidectin in each study. Prevention of the establishment of patent infections was evaluated by two treatments at a monthly interval at three different time points before and after challenge infection. Curative efficacy was tested by one or three treatments after the onset of patency. Worm counts at necropsy were used for efficacy calculations. RESULTS: In Study 1, the control group had a geometric mean (GM) of 28.8 adult nematodes and the single treatment group had a GM of 3.4 (efficacy 88.3%). In Study 2, the control group had a GM of 14.3, the prevention group had a GM of 0 (efficacy 100%), while the treatment group had a GM of 0.1 (efficacy 99.4%). In Study 3, the GM worm burden in the control group was 32.6 compared to 0 in all three prevention groups (efficacy 100% for all of those groups). CONCLUSIONS: The monthly administration of Advocate® reliably eliminated early larval stages and thereby prevented lung damage from and patent infections with A. abstrusus in cats. Regarding treatment, a single application of Advocate® reduced the worm burden, but it did not sufficiently clear the infection. In contrast, three monthly treatments were safe and highly efficacious against A. abstrusus.

Efficacy of a moxidectin/imidacloprid spot-on formulation (Advocate®) for the treatment of Troglostrongylus brevior in naturally infected cats in a field study in Greece.

BACKGROUND: Troglostrongylus brevior is a lungworm of wild felids that recently has been recognized as agent of severe respiratory disease in domestic cats in Mediterranean and Balkan countries. Nevertheless, the information on treatment options for feline troglostrongylosis is still poor. The aim of this pilot field trial was to evaluate the efficacy of the spot-on formulation containing 1% w/v moxidectin and 10% w/v imidacloprid (Advocate® spot-on solution for cats, Bayer Animal Health GmbH) in the treatment of T. brevior infection in naturally infected cats in Greece. METHODS: The trial was a negative control, multicentre, clinical efficacy study conducted according to the standards of Good Scientific Practice (GSP). Sixteen cats in two study sites, naturally infected with T. brevior, were allocated to an untreated control group (G1, n = 8) or a treatment group (G2, n = 8), according to a randomization list. Animals assigned to G2 were treated with Advocate® for cats on days 0 and 28 at the recommended dose rate and animals assigned to G1 received a rescue treatment with the same product on days 56 and 84. Efficacy was assessed on days 28 and 56 in G2 and on days 84 and 112 in G1 by faecal larval counts. The primary efficacy criterion was the absence of T. brevior first-stage larvae (L1) following treatment. Other efficacy parameters were the quantitative comparison of L1 presence before (baseline) and after one or two treatments in both groups. RESULTS: All G2 cats were negative for T. brevior L1 at the first post-treatment evaluation (100% efficacy) while G1 cats were persistently shedding L1. The difference of the mean number of L1 per gram between G2 and G1 was statistically significant (P < 0.001). All G1 cats were negative (100% efficacy) for T. brevior L1 at the first post-rescue-treatment evaluation. Therefore, treatment efficacy at study completion was 100% in both groups in terms of stopping the L1 shedding in the faeces of the animals. No adverse effects were observed during the study. CONCLUSIONS: These results indicate that Advocate® spot-on solution for cats represents an option for treating cats naturally infected with T. brevior.

Shedding of feline lungworm larvae and their infectivity to snail intermediate hosts after anthelmintic treatment.

Aelurostrongylus abstrusus and Troglostrongylus brevior are snail-transmitted helminths causing respiratory diseases in infected cats. The shedding of feline lungworm L1s and their infectivity to the snail intermediate host, after administration of anthelminthic products to cats, are poorly documented. To assess the efficacy of 8.3% fipronil, 10% (S)-methoprene, 0.4% eprinomectin and 8.3% praziquantel (i.e. eprinomectin formulation) and 10% imidacloprid/1% moxidectin (i.e. moxidectin formulation) against these nematodes and to determine the number of days post-treatment until viable L1s are released in the faeces, 384 animals were screened by faecal examination. Of the 54 positive animals (i.e., 14.1%; 7.3% A. abstrusus, 6.2% T. brevior and 0.5% coinfected), 36 were randomly allocated to four groups. Groups A and B were composed of cats positive for T. brevior and treated with the eprinomectin and with the moxidectin formulations, respectively, whereas cats in groups C and D were positive to A. abstrusus and treated with the eprinomectin and the moxidectin formulations, respectively. Prior to and every day after treatment, faecal samples were analysed by the Baermann technique and the number of larvae per gram of faeces determined, and again four weeks after treatment, to assess the efficacy of a single administration of the products. In addition, to evaluate the pre- and post-treatment infectivity of L1s to snail intermediate hosts, one/two snails per cat were infected with 100 L1s collected from the faeces of enrolled animals and then digested 28 days p.i. Based on L1s faecal counts, the efficacy of the eprinomectin and the moxidectin formulations at 28 days was 100% for both A. abstrusus and T. brevior, with a mean number of days of 7.9 ±â€¯1.2 in group A, 7.8 ±â€¯1.9 in B, 6.9 ±â€¯1.6 in C and 8.9 ±â€¯2.0 in D to become negative. Following the artificial digestion, active L3s of T. brevior and A. abstrusus were found in 160 (87.4%) experimentally infected snails. The results of this study demonstrate that a single administration of the two formulations is effective in the treatment of A. abstrusus and T. brevior infections and that during the post-treatment period live L1s are shed for up to 8.9 ±â€¯2.0 days. L1s of both lungworm species released in the faeces after drug administration are still able to reach the infective larval stage in the infected snails. Hence, preventative measures after the treatment of infected animals should include keeping cats indoors and disposal of their faeces for approximately 10 days to avoid environmental contamination and infection of gastropod intermediate hosts.

Efficacy of a novel topical combination of fipronil, (S)-methoprene, eprinomectin and praziquantel against larval and adult stages of the cat lungworm, Aelurostrongylus abstrusus.

The efficacy of a novel topical combination of fipronil 8.3% w/v, (S)-methoprene 10% w/v, eprinomectin 0.4% w/v, and praziquantel 8.3% w/v (BROADLINE(®),(1) Merial) against larval and adult Aelurostrongylus abstrusus lungworms in cats was assessed in a controlled laboratory study. The study included 48 purpose-bred, short-haired cats which were each inoculated with 225 infective A. abstrusus larvae. The cats were formed into eight blocks based on pre-treatment bodyweight and were then, within each block, randomly allocated to one of six treatment groups: untreated control; treated once when A. abstrusus were expected to be third-stage larvae (4 days post inoculation [dpi]), fourth-stage larvae (7 dpi), immature adults (14 dpi) or adult nematodes (32 dpi), or treated twice, once when A. abstrusus were expected to be third-stage larval and once again when A. abstrusus were expected to be adult nematodes (4 dpi+32 dpi). Cats weighing ≥ 0.8-2.5 kg received one 0.3 mL applicator and cats weighing >2.5-7.5 kg received one 0.9 mL applicator. For determination of the efficacy of treatments, lungworm larval counts were established on faecal samples collected from all cats 32, 39, 46, 53 and 60 dpi. At each occasion from 46 dpi on, cats treated with fipronil, (S)-methoprene, eprinomectin and praziquantel had significantly lower A. abstrusus larval counts than the untreated controls with percentage reductions of 91.6% (cats treated 14dpi; P=0.012), ≥ 98.9% (cats treated either 4 dpi, 7 dpi or 32 dpi; P<0.001) or >99.9% (cats treated 4 dpi+32 dpi; P<0.001) at 60 dpi. Thus, the novel topical combination of fipronil, (S)-methoprene, eprinomectin and praziquantel was highly effective in the prevention and treatment of A. abstrusus lungworm infection in cats.

Efficacy of a single topical application of Advantage Multi (= Advocate) Topical Solution (10% imidocloprid + 2.5% moxidectin) in the treatment of dogs experimentally infected with Crenosoma vulpis.

Crenosoma vulpis is a metastrongylid lungworm of canids causing chronic respiratory disease in dogs in parts of North America and Europe. The objective of this study was to determine the efficacy of imidacloprid 10% + moxidectin 2.5% (Advantage Multi/Advocate Topical Solution) against C. vulpis infection in experimentally infected dogs. Eighteen beagles (9 M, 9 F) were each given 100 infective third-stage larvae of C. vulpis. The 16 dogs (8 M, 8 F) with the highest faecal larval counts were stratified by gender and larval counts and randomly assigned to a treatment group. Group 1 received placebo only; group 2 was given a single topical treatment of Advantage Multi/Advocate (10 mg/kg imidacloprid/2.5 mg/kg moxidectin) at 4 weeks PI. Dogs were euthanised at 8 weeks PI and the lungs were removed and examined for the presence of adult worms by lung flush. The mean (geometric) number for adult C. vulpis recovered in untreated dogs was 70.0 (range 58 to 87) compared with 0.0 in animals treated with Advantage Multi/Advocate. The resulting efficacy against C. vulpis was 100%. The number of C. vulpis was significantly lower for treated dogs than the burden shown in the untreated group (p = 0.003).

Efficacy and safety of imidacloprid 10%/moxidectin 1% spot-on formulation in the treatment of feline aelurostrongylosis.

The objective of the present study was to evaluate the efficacy and safety of the antiparasitic spot-on formulation containing imidacloprid 10%/moxidectin 1% (Advocate, Bayer) in the treatment of natural feline infection with the lungworm Aelurostrongylus abstrusus (Nematoda, Strongylida). The efficacy of Advocate administered once was tested in comparison to a control oral formulation containing fenbendazole 18.75% (Panacur Intervet) administered over three consecutive days based on larvae per gramme of faeces (LPG), measured on days 28 +/- 2 following treatment and compared to counts on days -6 to -2. In total 24 cats treated either with Advocate (n = 12) or with Panacur (n = 12) were included. Mean LPG postbaseline (days 28 +/- 2) were low in both treatment groups, i.e., 0 LPG for Advocate and 1.3 LPG for Panacur. Reduction of post-baseline larval counts showed Advocate (100% reduction) to be superior in efficacy compared to the control product (99.29% reduction). No treated animals showed adverse events. This trial demonstrated that both Advocate spot-on formulation and Panacur oral paste are safe and effective in the treatment of aelurostrongylosis in cats. Future practical perspectives in feline medicine and the major advantages of the spot-on product compared to the oral paste are discussed.

Efficacy and safety of emodepside 2.1%/praziquantel 8.6% spot-on formulation in the treatment of feline aelurostrongylosis.

The objective of the present study was to evaluate the efficacy and safety of the antiparasitic spot-on formulation containing emodepside 2.1%/praziquantel 8.6% (Profender, Bayer) in the treatment of natural feline infection with the lungworm Aelurostrongylus abstrusus (Nematoda, Strongylida). Efficacy of Profender given once at the licensed dose was tested in comparison to a control oral formulation containing fenbendazole 18.75% (Panacur, Intervet) given over three consecutive days at the licensed dose. Efficacy assessment was based on larvae per gramme of faeces (LPG) counts, measured on days 28 +/- 2 following treatment and compared to counts on days -6 to -2. In total 24 cats treated either with Profender (n = 12) or with Panacur (n = 12) were included in the assessment of efficacy and safety. Mean LPG post-baseline counts (days 28 +/- 2) were 1.3 LPG for both Profender and Panacur, demonstrating similar efficacy of 99.38% for Profender and 99.29% for the control product. No treated animals showed adverse events. This trial demonstrated that both Profender spot-on formulation and oral paste Panacur are safe and effective in the treatment of aelurotrongylosis in cats. Future practical perspectives in feline medicine and the major advantages of the spot-on product compared to the oral paste are discussed.

Field efficacy of eprinomectin against a natural Muellerius capillaris infection in dairy goats.

The field efficacy of eprinomectin against a natural infection with Muellerius capillaris was evaluated in adult dairy goats. A total of 13 animals were included in a crossover treatment study. Animals were treated with eprinomectin (0.5 mg/kg) in the spring and again in the autumn of 2006, and monitored by enumeration of the lungworm larvae per gram of faeces (LPG). The reduction in LPG on days 7, 21 and 42 after treatment was used to evaluate the anthelmintic efficacy. Both in the spring and in the autumn a 100% reduction (P<0.01) in LPG was observed on days 21 and 42. These results illustrate that eprinomectin applied as a topical pour-on is a practical alternative to benzimidazole treatment of lungworms in dairy goats. No adverse reactions to the eprinomectin treatment were observed.

Efficacy of moxidectin 0.5% pour-on against swine nematodes.

Forty pigs with induced infections of Ascaris suum, Trichuris suis, Metastrongylus spp., Oesophagostomum dentatum and O. quadrispinulatum were assigned to five-dose groups of moxidectin 0.5% pour-on with eight pigs per dose group. The doses were: moxidectin, 0 (vehicle control), 0.75, 1.00, 1.25, and 1.50 mg/kg(-1) body weight. Worm egg counts (EPG) were made from fecal samples collected on Day 2 pretreatment and on Day 14 or 15 post-treatment. Animals were ranked according to the descending order of A. suum egg counts made on Day 2 and blocked in groups of five. Pigs in blocked groups were assigned randomly to each of the five dose groups. Treatment doses were calculated on the basis of weights taken on Day 1 and were administered topically from the neck to the base of the tail. Pigs were housed by pairs in individual pens provided with self-feeders and automatic waterers. Necropsies were performed on equal numbers of pigs from each treatment group on days 14 and 15 post-treatment. Adult and larval worms were collected, identified and counted by standard parasitological techniques. All counts were transformed by Y=log10 (count+1) transformation prior to analysis. A two-way analysis of variance was conducted and treatment effect was tested for significance at the 5% level. Efficacies based on geometric means and optimal doses were as follows: Ascaris suum, 98.3% at 1.25; Metastrongylus spp., 100% at 0.75; Oesophagostomum quadrispinulatum, 100% at 1.50; and Trichuris suis, 93.5% at 0.75. Efficacy for O. dentatum was from 81.3% to 100%; however, the average number of O. dentatum (30) was too small for significance. Two species of lungworms were present, Metastrongylus apri and M. pudendotectus but they were not speciated at necropsy. As reported for several anthelmintics, the efficacy of moxidectin was variable for Trichuris. The highest efficacy was in the 0.75 dose group with six pigs harboring a few or no worms. The lowest efficacy was in the 1.25 group with only two pigs harboring a few or no worms.

Use of fenbendazole for long-term control of protostrongylid lungworms in free-ranging Rocky Mountain bighorn sheep.

In an effort to control Protostrongylus spp. in a Rocky Mountain bighorn sheep herd (Ovis canadensis canadensis) of approximately 30 animals, fenbendazole-medicated salt was placed on the Stillwater bighorn winter range in southcentral Montana (USA) for four consecutive winters, 1990 to 1993. Sheep of all age and sex classes were observed using the medicated salt throughout the study period. Prevalence and average number of lungworm larvae per gram of bighorn feces declined significantly (P < 0.05) from pretreatment levels (1987 to 1989), and remained low throughout the study period. Free-choice availability of fenbendazole-medicated salt is a potentially effective management tool for long-term control of protostrongylid lungworm.

[Effect of flubendazole on Muellerius capillaris in mouflon]. / Ucinnost flubendazolu proti Muellerius capillaris mufloní zvere.

Muellerius capillaris is the most important pneumonematode of the mouflon kept in the Czech Republic. Particularly high values of prevalence and intensity of infection are recorded in the mouflon stocks kept in preserves. Numerous anthelmintics can be used for pharmacotherapy. Adulticide effect of the drug in verminous lung foci should be the aim of administrations. The aim of this study was to test anthelmintic efficacy of flubendazole (FBZ) against M. capiollaris in mouflon. The study was conducted in 16 mouflons in a small game preserve. An FBZ dose of 3 x 15 mg/kg live weight was chosen to be tested. Samples of mixed droppings were collected before treatment, during it and after its termination. LPG values were determined by larvoscopic examinations. Four (2 x 2) mouflons were shot on day 7 and 14 after treatment termination and they were subjected to detailed helminthologic examinations (macroscopic description of pulmonary verminous lesions, larvoscopy of verminous foci and mucus smears from the respiratory tract, larvoscopy of individual droppings). The game were extremely willing to ingest the drug applied with feed, the dosing schedule being confirmed. Pre-treatment LPG values of mixed droppings (Fig. 1) fell rapidly after the treatment started, and the excretion of M. capillaris larvae completely terminated beginning on day 7 after treatment termination. Pulmonary and coprological LPG findings in the shot mouflons (their description is in Tab. I) were minimum, in one animal only (Tab. II), in the others the findings were zero. Macroscopic findings (Fig. 2) showed that all shot mouflons had suffered from the infection to a large extent before treatment. The therapeutic efficacy of FBZ administered at a dose of 3 x 15 mg/kg of body weight can be in general evaluated highly positively. The drug administration quickly stopped larvae excretion in the mouflon droppings due to adulticide effect in the verminous foci of the lungs.

Between goat-farm biological variability of the nematode Muellerius capillaris first-stage larvea. Influence of anthelmintic treatment.

Seven dairy-goat farms from the centerwest of france were investigated for morphology and ecology of first-stage larvae (L1) of Muellerius capillaris before and after treatment of goats with febantel, a probenzimidazole anthelmintic. The lengths, survivals at 20 and -20 degrees C, and infectivity of L1 to intermediate host Helix aspersa, were different between farms. The between farms differences in survivals were reduced after treatment of goats with febantel. The observed between farm differences in L1 did not seem to be related to farm characteristics (intensity of treatments, susceptibility to febantel, and intermediate host species).

Effects of milbemycin D on adult Angiostrongylus cantonensis in rats.

Effects of milbemycin D against adult Angiostrongylus cantonensis in rats were examined. The first-stage larval counts in rat faeces (larvae per gram of faeces per female worm recovered, LPG/female) were most conspicuously reduced in the group treated with nine consecutive weekly doses of 5.0 mg/kg. The effect was more marked in the group treated with five or ten successive daily doses of 5.0 mg/kg than the group treated with a single dose of 25.0 or 5.0 mg/kg. Host lung-body weight ratio and number of recovered worms were reduced significantly only in the group treated with five or ten successive daily doses of 5.0 mg/kg. These results suggest that the action of milbemycin D on the reproductive system of the worms might be differentiated from its killing action. The in vitro motility of females recovered from rats medicated with nine consecutive weekly doses of 5.0 mg/kg was inhibited, and almost all females and males were semitransparent and colourless. Results obtained from sectioned worms showed little content in their digestive tracts and uteri. In addition, there were few eggs and first-stage larvae in the lung tissues of treated rats. These suggest that milbemycin D affects the reproductive functions of the worms through an indirect mode of action including paralysis and inhibition in food intake and energy and/or synthetic metabolism.

Studies on anthelmintic effects of flubendazole and mebendazole on the rat lungworm Angiostrongylus cantonensis in mice and rats.

Flubendazole and mebendazole given orally at 10 mg/kg/day 5-7 days post-infection (total 30 mg/kg) were found to eliminate 93-100% of Angiostrongylus cantonensis larvae in mice and rats. No significant difference was observed between the effects of the 2 drugs. The effectiveness of the drugs decreased with the increase in days post-infection on which medication was administered. It was found possible to treat A. cantonensis adults in rats by administering flubendazole or mebendazole at 10 mg/kg/day for 10 consecutive days. The drugs exhibited better anthelmintic efficacy in a divided dosing regimen than in a single dosing regimen.

Effects of diethylcarbamazine on the motility of Angiostrongylus cantonensis and Dirofilaria immitis.

Effects of piperazine derivatives, especially of diethylcarbamazine (DEC) on adult Angiostrongylus cantonensis and Dirofilaria immitis were examined. Piperazine (3 X 10(-5)-10(-4) M) paralyzed A. cantonensis and the action was antagonized by picrotoxin. 1,1-dimethyl-4-phenylpiperazinium iodide (DMPP) (10(-5)-10(-4) M) caused contraction but little effect was produced by strychnine. An inhibitory effect on untreated preparations was caused by lower concentrations (3 X 10(-6)-10(-5) M) of diethylcarbamazine citrate (DEC) and also on the preparations contracted by eserine. A stimulatory effect was also seen when higher concentrations (10(-4)-3 X 10(-4) M) of this drug were applied to both preparations. The inhibitory action of DEC was antagonized by gabergic antagonists such as picrotoxin and bicuculline, but not by alpha-adrenergic antagonists like dibenamine and phentolamine. When the worm preparation was paralyzed by strychnine or hexylresorcinol (inhibitors of the release of acetylcholine in this worm), the stimulatory effect of DEC was blocked, but pyrantel (a nicotinic cholinergic agonist) contracted the paralyzed preparation. However, the effect of DEC on D. immitis (10(-7)-3 X 10(-4) M) was inhibitory, and this action was also antagonized by picrotoxin. These results suggest that the DEC inhibitory and stimulatory action is through the gabergic and cholinergic mechanisms in adult A. cantonensis and D. immitis.