Enhanced absorption of pour-on ivermectin formulation in rats by co-administration of the multidrug-resistant-reversing agent verapamil

The effect of verapamil, a multidrug-resistance (Mdr)-reversing agent on the absorption of a pour-on formulation of ivermectin was evaluated in rats. Absorption of ivermectin was effectively enhanced (40%) by the presence of verapamil, suggesting that absorption of ivermectin involves Mdr-P-glycoprotein and that verapamil should act as a competitive inhibitor for the transport and extrusion of ivermectin by P-glycoprotein. This hypothesis is consistent with other studies describing verapamil as a blocking agent of P-glycoprotein involved in the efflux of ivermectin in a resistant strain of Haemonchus contortus. Received: 12 April 1999 / Accepted: 6 May 1999     

Influence of verapamil on the pharmacokinetics of the antiparasitic drugs ivermectin and moxidectin in sheep

P-Glycoprotein (P-GP) is a transport protein that participates in the mechanism of active secretion of different molecules from the bloodstream to the gastrointestinal tract. The aim of the current work was to evaluate the effect of verapamil, a P-GP substrate, on the pharmacokinetic behaviour of the anthelmintics ivermectin and moxidectin in sheep. Thirty-two sheep were divided into four groups and treated orally with either ivermectin or moxidectin alone (200 µg/kg) or co-administered with verapamil at 3 mg/kg (three times at 12 h intervals). Blood samples were collected over 30 days post-treatment and plasma was analysed to determine ivermectin and moxidectin concentrations by HPLC. The ivermectin peak concentration was significantly higher (P=0.048) after ivermectin plus verapamil, compared with the ivermectin alone treatment. Ivermectin plasma availability was significantly higher following co-administration (P=0.022). Verapamil had no effect on the kinetics of moxidectin. The significant alteration in the plasma disposition of ivermectin in sheep induced by verapamil, possibly due to interference with a P-GP-mediated elimination mechanism, may have an important impact on efficacy against resistant- or rate-limiting-parasites and on the persistency of its antiparasitic activity.     

Investigations on the seasonal patterns of strongyle infections in grazing lambs, and the occurrence of anthelmintic resistance on sheep and goat farms in western Anatolia, Turkey

The seasonal patterns of strongyle infections in untreated, weaned lambs were determined on four governmental farms during a grazing season. In three farms, the infection level (predominantly Teladorsagia spp. and Trichostrongylus spp.) measured by egg counts or worm burdens remained low throughout the study; higher egg counts mainly caused by Haemonchus contortus were transiently recorded on the fourth farm. Significant body weight gains were observed in all groups, but they varied between farms irrespective of the level of strongyle infections, suggesting that the economic effectiveness of anthelmintic treatments of weaned lambs is doubtful under the extensive grazing conditions and the hot, dry climate in the region. In the second part of the study, faecal egg count reduction tests were performed for albendazole, thiabendazole, tetramisole and ivermectin on 12 sheep and goat farms to provide first information on anthelmintic resistance in trichostrongyles of small ruminants in Turkey. There was no hint of benzimidazole resistance, and unequivocal evidence of ivermectin resistance was missing. In contrast, tetramisole resistance was detected on one sheep farm.     

First report of multiple drug resistance in trichostrongyles affecting sheep under field conditions in Italy

Drug resistance in sheep gastrointestinal trichostrongyles is a cosmopolitan major constraint to small ruminant production. Despite reports that anthelmintic drug resistance has become common, there are limited information on the presence of drug resistance in Italy. The purpose of this study was to determine the effect of four anthelmintics to control infection in sheep in central Italy. Fifty sheep with fecal egg counts (FEC) ≥150 eggs per gram were selected on each of three farms (n = 150 total sheep) which were randomly allocated to one of five groups. Groups were treated with febantel, levamisole, ivermectin, or moxidectin while the fifth group acted as the control group. A FEC reduction test (FECRT) was conducted on each animal and the mean FEC of each treatment group was compared to that of the control group within farm. Resistance was declared when percentage reduction (R) <95% and the lower 95% confidence interval was <90%. Levamisole (mean R = 89%) resistance was found on all farms and ivermectin (mean R = 93%) resistance was found on two of the three farms. Posttreatment larval cultures showed the presence of Teladorsagia (Ostertagia) circumcincta and Trichostrongylus spp. larvae. Febantel (mean R = 96%) and moxidectin (mean R = 100%) remained effective. This study suggests that drug resistance in sheep gastrointestinal trichostrongyles is present in central Italy and a potential problem which would justify a broader nationwide geographical investigation. An erratum to this article can be found at     

The effect of verapamil on in vitro susceptibility of promastigote and amastigote stages of <Emphasis Type="Italic">Leishmania tropica</Emphasis> to meglumine antimoniate

Pentavalent antimonials are the standard treatment for cutaneous leishmaniasis (CL) with low efficacy and resistance is emerging. CL is increased significantly in respect to incidence rate and expanding to new foci. In the present study, the effect of verapamil on in vitro susceptibility of promastigote and amastigote stages of Leishmania tropica to meglumine antimoniate (MA, Glucantime) was evaluated using colorimetric assay (MTT) and in a macrophage model, respectively. Verapamil, as a calcium channel blocker, affects drug uptake by preventing of drug efflux from the cells. In promastigote form, several concentrations of MA with or without verapamil showed significant decrease (P < 0.05) in optical density. The overall mean IC₅₀ value with combination of MA plus verapamil (IC50 = 116.03 μg/ml) was significantly less than MA (IC50 = 225.14 μg/ml) alone (P < 0.05) for promastigote stage. Similarly, the amastigote stage was more susceptible to treatment with MA plus verapamil to that of MA alone (P < 0.05). Analysis of overall effect of different concentrations of MA alone, compared with combination of MA plus verapamil by mean infection rate of amastigotes in each macrophage showed a significant difference (P < 0.05).These findings indicated some degree of synergistic effects between MA and verapamil on in vitro susceptibility of L. tropica to MA. Further works are required to evaluate this synergistic effect on animal model or volunteer human subjects.     

Prevalence of multiple anthelmintic resistant gastrointestinal nematodes in dairy goats in a desolated tract (Pakistan)

This paper presents the first report of anthelmintic resistance (AR) in dairy goats in a desert (Pakistan). Three breeds of dairy goats, i.e. Dera Din Panah, Pak Angora and Beetal, kept at Government Livestock Farm, Rakh Khairewala, district Jhang/Layya, Pakistan, were surveyed for gastrointestinal nematodes (GINs) resistant to commonly used three anthelmintics, i.e. benzimidazole, levamisole and ivermectin. Sixty animals of each breed were selected randomly on the basis of their weight and egg count. Three commonly used anthelmintics, viz., oxfendazole (three different preparations of oxfendazole: fendamex, oxazole, systamex), levamisole and ivermectin, were given at the recommended dose to five groups while one untreated group was kept as control for each breed. Faecal egg counts, faecal egg count reduction test, postmortem worm count and copro-culture were performed to assess the efficacy of selected anthelmintics. The prevalent species of GINs exhibited resistance against all three preparations of oxfendazole. Levamisole in two breeds and ivermectin in all the breeds led to reduction (P ≤ 0.05) of prevalent species of GINs in both flocks. Haemonchus controtus and Trichostrongylus species exhibited the presence of resistance against oxfendazole preparations which exhibited low efficacy (P ≥ 0.05). The farm management practices along with the results of the present study revealed the presence of multiple anthelmintic resistant GINs of dairy goats kept in a desolated tract.     

Efficacy of ivermectin and moxidectin injection against larvae of Wohlfahrtia magnifica (Diptera: Sarcophagidae) in sheep

 The therapeutic efficacies of ivermectin (Ivomec injection, Merck Sharp & Dohme B.V.) and moxidectin (Cydectin 1% injection, American Cyanamid Company) were evaluated in sheep naturally infested with larvae of Wohlfahrtia magnifica. Sheep were randomly allocated to one of the 2 groups, each consisting of 19 animals. Sheep in one group received ivermectin and those in the other, moxidectin by subcutaneous injection at a dose of 0.2 mg/kg body weight. Evaluation was performed at 19, 24, 28, 39, 43, 48, 52, 63, 67, 72, 87, 96, 120, 144 and 168 h after treatment. At 144 and 168 h post-treatment, late third-instar larvae were collected from wounds of four sheep in both groups and from untreated, infested sheep. These larvae were reared in the laboratory to assess adult emergence. Neither ivermectin nor moxidectin was effective as a rapid acting treatment or as a long-term, or even short-term, prophylactic. Despite the treatment, 30–40% of sheep had live larvae at every evaluation. Although larvae disappeared from the wounds of some sheep in both groups after the treatment, the wounds in these animals failed to recover and were reinfested by larvae of W. magnifica. On day 7 post-treatment the trial had to be finished because the majority of treated sheep were severely infested by Wohlfahrtia maggots. The average number of infested sheep in the two groups and the number of adults that were produced from larvae collected from treated sheep indicate that ivermectin and moxidectin did not differ significantly in efficacy. Received: 22 May 1995 / Accepted: 16 June 1995     

Improving liveweight gain of lambs infected by multidrug-resistant nematodes using a FECRT-based schedule of treatments

The aim of this study was to compare the liveweight gain of lambs, infected by multidrug-resistant nematodes, treated by conventional schemes of helminth control or using a schedule based on fecal egg count reduction test (FECRT). The flock was selected after a FECRT (experiment 1) which revealed a parasite population resistant to benzimidazoles, imidazothiazoles, macrocyclic lactones (ivermectin), salicylanilides, nitrophenols, and organophosphates. Despite the parasite resistance to ivermectin (an avermectin), the moxidectin (a milbemycin) was effective against the gastrointestinal nematodes (PR?>?90 %). In experiment 2, 48 suckling lambs were distributed in four randomized blocks (G1, G2, G3, and G4) by previous body weighings. G1 was kept as untreated control; G2 was treated following a FECRT-based schedule with drugs chosen based on fecal analysis (first drench with moxidectin, second drench with a combination of moxidectin and levamisole, and third drench with praziquantel, an anti-cestode drug); G3 and G4 received three drenches with ivermectin or disophenol, respectively. Body weighings and fecal analysis of these lambs were performed every 2 weeks over a 98-day period. An effective control of gastrointestinal nematodes was obtained with two nematicidal drenches following the FECRT-based schedule of treatments. On the other hand, eggs per gram of feces (EPG) counts were no different among untreated control, G3, and G4. Lambs treated using the FECRT-based schedule had the greatest liveweight gain among the groups tested. Additionally, liveweight gain was no different among the groups G3, G4, and G1. The FECRT-based schedule of anthelmintic treatments was beneficial regarding productivity and sustainability of helminth control in lambs infected by multidrug-resistant nematodes.     

Flow cytometry analysis of drug transport mechanisms in Haemonchus contortus susceptible or resistant to anthelmintics

The role of membrane drug-transport mechanisms in resistance to anthelmintics was examined using a flow cytometry method. This method was adapted from assays developed for the study of similar mechanisms in tumor cells. Rhodamine 123, a P-glycoprotein transport probe, associated with the reversal agent verapamil gave a significantly higher level of green fluorescence in Haemonchus contortus-resistant eggs as compared with that of susceptible eggs. In the same way, verapamil-bodipy, a new fluorescent probe for the detection of multidrug resistance in cells, showed a significantly higher degree of binding to resistant eggs. The results confirm those obtained with biological drug assays using both anthelmintics and verapamil and provide a quantitative and effective methodology for the functional study of multidrug resistance in nematodes. Received: 12 June 1998 / Accepted: 21 July 1998     

The efficacy of strategic treatments with ivermectin pour-on against trichostrongylid and lungworm infections in first year grazing calves in northern Germany.

Three groups of 8 first year grazing calves each were either left untreated as controls (group 1), or were treated with 10 mg levamisole spot-on/kg bodyweight (group 2) or with 0.5 mg ivermectin pour-on/kg bodyweight 3, 8, and 13 weeks after turnout (group 3), respectively. Egg counts, herbage larval counts, worm counts of tracer calves, pepsinogen concentrations and weight gains showed a high efficacy of the strategic treatment in group 3 against gastrointestinal nematodes. The calves of group 1 and 2 developed clinical signs of parasitic bronchitis whereas the group 3 animals remained clinically healthy. The strategic treatment with ivermectin cleaned the respective pasture from infective lungworm larvae.     

Critical tests evaluating efficacy of moxidectin against small strongyles in horses from a herd for which reduced activity had been found in field tests in Central Kentucky

Critical tests were performed in 2009 and 2010 in four 2-year-old horses naturally infected with internal parasites. The horses were from a herd (Farm MC) where reduced activity of ivermectin and moxidectin on small strongyles was demonstrated previously from EPG (eggs/gram of feces) data in field tests. Also, in critical tests in horses from the same herd, ivermectin was less effective on immature small strongyles in the lumen of the large intestine than when the drug was first marketed. The main interest in the present critical tests was to determine the efficacy of moxidectin (400 μg/kg) on small strongyles. This was done to try and find indications of why there has been a return of strongyle EPG counts sooner after treatment in field tests than when moxidectin was first commercially available. Removal of adult small strongyles for the four treated horses was >99% to 100%. Efficacy on immature (L₄) small strongyles was 82%, 96%, 98%, and >99% for the individual horses. Identification of small strongyles recovered from two of the horses revealed that three genera and 11 species were present. Specimens of Cylicocyclus ashworthi are reported for the first time in horses in Kentucky although eggs of this species have been identified. Moxidectin, in the present study, was excellent on removing adult small strongyles but was less effective on immatures (L₄) in the intestinal contents. The question as to why moxidectin efficacy on small strongyles has declined in field tests may have been answered at least to a certain extent. It seems that a significant factor is “quick development” of a few remaining immatures in the gut lumen of horses. Also, possible activity may have decreased on encysted stages in the large intestinal lining. In any event, after treatment of some horses with moxidectin, the life cycle of small strongyles is shorter now than at the onset of usage of this compound.     

Efficacy of macrocyclic lactone endectocides against Boophilus microplus (Acari: Ixodidae) infested cattle using different pour-on application treatment regimes

The efficacy of pour-on formulations of three macrocyclic lactone endectocides (moxidectin, ivermectin, and eprinomectin) was evaluated on cattle against Boophilus microplus (Canestrini) using two different treatment regimes. A single application treatment regime with each endectocide showed that fewer ticks per calf were recovered from all treated calves than from untreated cattle, but the level of control among the three treatments was similar (range; 78.7-87.7%) against all stages of ticks on the calves at the time of treatment. The engorged female and egg mass weights of all treated ticks were less than that of untreated ticks. Among the treated groups, the ivermectin and eprinomectin-treated females weighed less and produced lower weight egg masses than those from moxidectin-treated cattle. In a double application treatment regime with a 4-d interval between treatments, there were fewer ticks per calf recovered from the treated cattle than from untreated cattle. In addition, all treated females weighed less and produced lower weight egg masses than those from untreated cattle. Control with moxidectin (90.3%) was lower than with either ivermectin (98.9%) or eprinomectin (99.7%). The mean female and egg mass weight of the ivermectin and eprinomectin-treated groups was also less than that of the moxidectin treatment. A single application treatment against either 18- or 20-d-old adult ticks indicated that both moxidectin and ivermectin were less effective against 20-d-old ticks that were nearer to completing their parasitic development on the animal. In contrast, eprinomectin was the only endectocide tested that was equally effective against both 18- and 20-d-old ticks.     

Field studies indicating reduced activity of ivermectin on small strongyles in horses on a farm in Central Kentucky

Field studies (n = 6) were completed on evaluation of activity of ivermectin (200 μg/kg) paste formulation against small strongyles in horses (foals, yearlings, and older animals) on a farm (Farm MC) in Central Kentucky in late 2006 and during 2007. A girth tape was used to estimate body weights which were then used to calculate the proper dose rate of ivermectin. The foals, yearlings, and some of the older horses were born and raised on the farm. However, most of the older horses which were not raised on the farm had been there for several years. The horse herd was given ivermectin exclusively, usually four times a year, since 1990. An exception was that during the foal’s period of life fenbendazole, pyrantel pamoate, and oxibendazole were given occasionally besides ivermectin. Efficacy of drug activity was determined by pretreatment and posttreatment counts of strongyle eggs per gram of feces (EPGs). Culture of strongyle eggs in feces from some of the horses showed that only small strongyle larvae were present. The research included two studies (A and B) in foals (n = 24) and four studies (C, D, E, and F) in yearlings (n = 13) alone or with older horses (n = 10). For each of the studies (B through F), there was a treated and a nontreated group. These groups were switched for each treatment, i.e., the treated group in one study was the nontreated group in the next study and vice versa. Eggs per gram of feces counts were determined at 1- or 2-week posttreatment intervals for 4 weeks for study A and 6 weeks for studies B through F. Also, for studies B, E, and F, counts of EPGs were done either two or three times during the third week posttreatment. The studies showed a similar posttreatment pattern of strongyle EPG counts beginning to return at about 4 weeks and increasing at 5 and 6 weeks posttreatment. Two horses in study E and one in study F had low EPG values toward the end of the third week posttreatment. The results of this ivermectin investigation showed that the strongyle EPG counts started returning about twice as quickly post-ivermectin-treatment of horses than when the drug was first marketed in the early 1980s.     

Effectiveness evaluation of several cattle anthelmintics via the fecal egg count reduction test

Utilizing groups of cograzed, naturally infected beef-type heifers, three fecal egg count reduction tests were conducted in the later months of 2007 at the University of Arkansas. Each test was 28 days in length consisting of individual animal fecal nematode egg counts and coprocultures. Both original and generic ivermectin injectable formulations were used in two of the tests at 0.2 mg/kg BW, with FECR percentages never exceeding 90% in either test. Oral fenbendazole was evaluated at 5 and 10 mg/kg BW, with FECR%'s exceeding 90% on all occasions, but with a precipitous drop when recently treated animals were treated at the lower dose. Evaluated in one test, injectable moxidectin given at 0.2 mg/kg BW resulted in egg count reductions of 96–92% (days 7 to 28). Also evaluated in one test, albendazole delivered orally at 10 mg/kg BW was 98% and 97% effective at 17 and 28 days post-treatment. For all tests, coprocultures conducted post-treatment contained only Cooperia spp. larvae (benzimidazole use), relatively unmodified percentages of Cooperia spp. and Haemonchus spp. larvae (ivermectin use), and primarily Cooperia spp. larvae with a small percentage of Haemonchus spp. larvae (moxidectin use).     

In vitro selection of Haemonchus contortus for benzimidazole resistance reveals a mutation at amino acid 198 of β-tubulin

Benzimidazoles were the first broad-spectrum anthelmintics and are still in use today against gastro-intestinal nematodes of ruminants such as Haemonchus contortus. Benzimidazoles block the polymerization of nematode microtubules. However, their efficacy is jeopardized by the spread of drug-resistant parasites that carry point mutations in β-tubulin. Here we use a novel in vitro selection—in vivo propagation protocol to breed drug-resistant H. contortus. After 8 generations of selection with thiabendazole an in vitro resistance factor of 1000 was reached that was also relevant in vivo in infected sheep. The same procedure carried out with ivermectin produced only a moderate resistance phenotype that was not apparent in sheep. Cloning and sequencing of the β-tubulin genes from the thiabendazole-resistant H. contortus mutants revealed all of the isotype 1 alleles, and part of the isotype 2 alleles, to carry the mutation glutamate¹⁹⁸ to alanine (E198A). An allele-specific PCR was developed, which may be helpful in monitoring the prevalence of alanine¹⁹⁸ encoding alleles in the β-tubulin isotype 1 gene pool of H. contortus in the field.     

Absence of ivermectin resistance in a survey on dairy goat nematodes in France

Anthelmintic resistance is very prevalent in ruminant strongyle populations, especially in goats. Several occurrences of multiple anthelminthic resistances have been reported in goat flocks throughout the world, including resistance to the most recent macrocyclic lactones. A faecal egg count reduction test was conducted to detect resistance to ivermectin in French goat flocks. Thirty goats per flock were randomly selected in 22 flocks and allocated into two groups of 15 animals: an untreated control group and an ivermectin-treated group (0.3 mg/kg BW per os). Individual faecal egg counts and pooled larval cultures were performed 16-17 days after anthelmintic treatment for control and treated groups. FECR’s were calculated for treated group vs. control one and when <95/100, were considered as indicative of anthelmintic resistance. FECR results indicated the absence of ivermectin resistance in nematode populations from all the 22 goat farms. The nematode genera involved in control groups were of Teladorsagia/Trichostrongylus, Haemonchus and Oesophagostomum/Chabertia types.     

Evaluation of the effect of simulated rainfall on the efficacy of Ivomec Pour-on against Cooperia spp. infection in cattle

Four controlled studies, one each in Australia, Germany, the United Kingdom, and the United States, involving 30 calves each were conducted to evaluate the effect of simulated rainfall on the efficacy of Ivomec Pour-On against infections of Cooperia spp. At 3 weeks before treatment the calves were infected orally with third-stage larvae of Cooperia spp. In each study a recent, locally derived field isolate was used. The calves were allocated by restricted randomization based on body weight within sex to one of the following treatments: unmedicated control with no rain, Ivomec Pour-On with no rain, Ivomec Pour-On with rain starting at 40 min before treatment, Ivomec Pour-On with rain starting at 10 min after treatment, and Ivomec Pour-On with rain starting at 60 min after treatment. Ivomec Pour-On was applied topically at a dose rate of 1 ml/10 kg body weight (500 μg ivermectin/kg body weight). The simulated rainfall was equivalent to a heavy shower of approximately 12.5 mm of water during a 30-min period. The calves were necropsied for worm counting at 14 or 15 days after treatment. An evaluation of the pooled data showed that as compared with the untreated controls, the Ivomec Pour-On-treated calves with no rain had significantly (P < 0.01) fewer C. oncophora (>99%), C. punctata (>99%), C. surnabada (>98%), and combined Cooperia spp. (>99%). The reduction in Cooperia numbers noted for calves exposed to simulated rainfall was >96% for all Cooperia species, regardless of when the rainfall started relative to the application of Ivomec Pour-On. There was no significant (P > 0.1) difference between the Ivomec Pour-On-treated calves with no rain and the pooled groups with simulated rainfall or between the group with rain before treatment and the pooled groups with rain after treatment. Ivomec Pour-On was highly effective against established infections of Cooperia spp. when applied to wet animals or to animals becoming wet shortly after treatment. Received: 4 December 1998 / Accepted: 11 February 1999     

Oesophagostomum spp. in pigs: resistance to reinfection

For a study on the occurrence of resistance to reinfection with porcine nodular worm species, pigs were infected twice weekly with 1,000 infective larvae (L₃) of Oesophagostomumquadrispinulatum for 8 weeks. All pigs, including noninfected controls, were then treated with fenbendazole. At 10 days after treatment, all pigs received a single challenge inoculation of 5,000 L₃ of either O. dentatum or O. quadrispinulatum, respectively. Pigs were slaughtered at 6 weeks after the challenge infection for determination of their worm burdens. The pigs trickle- and challenge-infected with O. quadrispinulatum had significantly lower egg excretion levels (P < 0.01) and worm burdens (P < 0.05) than challenge control pigs, thus indicating some degree of host immunity against the homologous challenge infection. No resistance to reinfection was evident for the heterologous challenge infection. This study elucidates further aspects of the interaction between nodular worm species in the pig. Received: 17 April 1998 / Accepted: 8 June 1998     

A rapid colorimetric assay for the quantitation of the viability of free-living larvae of nematodes in vitro

With increasing drug resistance in gastrointestinal parasites, identification of new anthelmintics is essential. The non-parasitic nematode Caenorhabditis elegans is used extensively as a model to identify drug targets and potential novel anthelmintics because it can be readily cultured in vitro. Traditionally, the assessment of worm viability has relied on labour-intensive developmental and behavioral assays. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide-formazan (MTT-formazan) colorimetric assay uses metabolic activity as a marker of viability in mammalian cell culture systems and has been applied for use with filarial nematodes. In the present study, this assay has been optimized and validated to rapidly assess the viability of C. elegans after drug treatment. Living, but not dead, C. elegans take up MTT and reduce it to the blue formazan, providing visual, qualitative, and quantitative assessment of viability. MTT at a concentration of 5 mg/ml with 3 h incubation was optimal for detecting changes in viability with drug treatment. We have applied this assay to quantitate the effects of ivermectin and short-chain alcohols on the viability of C. elegans. This assay is also applicable to first-stage larvae of the parasitic nematode Haemonchus contortus. The advantage of this assay is the rapid quantitation in screening drugs to identify potential anthelmintics.     

Anthelmintic activity of KSI-4088 against Caenorhabditis elegans

Anthelmintic resistance is a serious global problem because of the worldwide spread of resistant nematodes in animals and humans. This has triggered increasing investment in research for new anthelmintics. Over the past decade, Caenorhabditis elegans has become a popular model organism for parasitic nematode research, and many examples have been published to illustrate its use. In this study, we investigated the effect of KSI-4088 on the egg hatching, larval development, and migration of the nematode worm C. elegans compared with ivermectin and levamisole (well-known anthelmintic drugs). KSI-4088 demonstrated anthelmintic activity on all assays of C. elegans. The anthelmintic activity of KSI-4088 on egg hatching and larval development showed especially strong activity, but assays showed that ivermectin and levamisole had no effects on C. elegans. In addition, KSI-4088 was capable of producing a change in the timing of the development of the worms at the L1–L3 and L4 stage. Also, we demonstrate that C. elegans L3–4 are more sensitive than adults to KSI-4088 in assay of migration. Our results indicate that KSI-4088 is an active anthelmintic compound that should be further investigated with the aim of developing a potent drug against nematodes.