Dose confirmation studies for monepantel, an amino-acetonitrile derivative, against fourth stage gastro-intestinal nematode larvae infecting sheep

Hosking, B. C.; Dobson, D. P.; Stein, P.A.; Kaminsky, Ronald; Bapst, B.; Mosimann, Denis; Mason, P; Seewald, Wolfgang; Strehlau, G.; Sager, Heinz

doi:10.1016/j.vetpar.2008.11.028

Cited by 34 publications

(28 citation statements)

References 24 publications

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“…The controlled efficacy studies used both experimentally and naturally infected sheep that were treated when nematode burdens were at either the adult or fourth larval stage, and the experimental designs of the new studies (including numbers of animals) were comparable to those described in Hosking et al 2008Hosking et al , 2009aBustamante et al 2009;Kaminsky et al 2009 andSager et al 2009. Thus, pooling of data for this present analysis was valid (Vercruysse et al 2001).…”

Section: Methodsmentioning

confidence: 99%

“…The efficacy of monepantel has recently been disclosed in a series of publications reviewing dose determination (Hosking et al 2008;Kaminsky et al 2009), dose confirmation (Bustamante et al 2009;Hosking et al 2009a;Sager et al 2009) and field efficacy studies (Hosking et al 2009b;Mason et al 2009). However, these publications only reported the results of individual studies (dose determination and confirmation) or individual farm sites within studies (field efficacy).…”

Section: Introductionmentioning

confidence: 99%

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A pooled analysis of the efficacy of monepantel, an amino-acetonitrile derivative against gastrointestinal nematodes of sheep

et al. 2009

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Monepantel is the first compound from the amino-acetonitrile derivative class of anthelmintics to be developed for the control of gastrointestinal nematodes of sheep. An analysis of pooled data from a series of controlled studies is reported providing a single point of efficacy (+/- 95% confidence interval) for each gastrointestinal nematode tested at the fourth larval and/or adult stages. For most nematode species, the pooled efficacy was greater than 99%, and for the remaining few species, efficacy was greater than 90%. These data are well supported by field studies conducted across five countries, where the pooled efficacy (on the basis of fecal worm egg count reduction) was in most cases, greater than 99% (depending on the calculation used). Monepantel is highly effective when administered to sheep at 2.5 mg/kg, and its introduction as a new anthelmintic for sheep is timely, given the problems with anthelmintic resistance that the world's sheep farmers are now experiencing.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

A pooled analysis of the efficacy of monepantel, an amino-acetonitrile derivative against gastrointestinal nematodes of sheep

et al. 2009

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“…In six of these studies (from Australia and Switzerland), additional groups of sheep were treated at 1.25 mg/kg, and this data was used to evaluate effects of breed and gender when sub-optimal doses of monepantel were administered. The studies used both experimentally and naturally infected sheep, that were treated when nematode burdens were at either the adult or fourth-larval stage, and as the experimental designs were comparable to those previously published (Bustamante et al 2009;Hosking et al 2008Hosking et al , 2009aKaminsky et al 2009;Sager et al 2009), pooling of data for this present analysis was considered acceptable (Vercruysse et al 2001). …”

Section: Methodsmentioning

confidence: 99%

“…Monepantel is the first molecule from the AADs to be developed for livestock (Kaminsky et al 2008b) and its efficacy has been extensively investigated in dose determination (Hosking et al 2008;Kaminsky et al 2009) and dose confirmation (Hosking et al 2009a;Sager et al 2009) studies. However, these authors reported only the results of individual studies.…”

Section: Introductionmentioning

confidence: 99%

The effect of sheep breed, age, and gender on the pharmacokinetics and efficacy of monepantel, an amino-acetonitrile derivative

et al. 2009

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This analysis investigated the influence of breed and gender on the pharmacokinetics of monepantel, and influence of breed, age, and gender on its efficacy against gastrointestinal nematodes of sheep. In a comparison of pharmacokinetic profiles from two studies, Merino lambs had significantly greater maximum concentrations of monepantel and monepantel sulfone, and faster times to reach these concentrations than Dorset cross lambs. Males had a statistically greater area under the curve (0-504 h) than females for monepantel sulfone. The biological relevance of these relatively small differences is unclear because efficacy was not evaluated in these studies. For efficacy, a breed effect existed for some nematodes when sheep were treated at a sub-optimum dose (1.25 mg/kg). There were no gender effects between sheep infected with adult parasites and treated at 1.25 mg/kg but there were differences between females and males treated at this dose when infected with fourth-stage larvae of Haemonchus contortus, Teladorsagia circumcincta, Trichostrongylus colubriformis, and Cooperia curticei. There were no breed or gender differences for sheep treated at the recommended dose (2.5 mg/kg). There was a potential trend for declining efficacy with increasing animal age for fourth-stage Trichostrongylus axei. This analysis demonstrated that, similarly to what is observed with other anthelmintics, the pharmacokinetics and efficacy of monepantel can vary with factors like breed, age, and gender. Identifying these covariates is important for understanding inter-individual variability in drug response. While further investigation is warranted, correctly treating sheep at the recommended dose of 2.5 mg/kg appears to mitigate any associated risk.

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“…Many authors reported the efficacy of MOP against adult H. contortus and also against the fourth larval stage (e.g. Baker et al, 2012, Hosking et al, 2009, Sager et al, 2012. However, the information about its effect against the lower larval stages or eggs of H. contortus has not been available yet.…”

Section: Introductionmentioning

confidence: 99%

Efficacy of monepantel against lower developmental stages of a multi-resistant and susceptible Haemonchus contortus isolates: an in vitro study

et al. 2013

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SummaryMonepantel (MOP) belongs to a new class of anthelmintic compounds, the amino-acetonitrile derivates, which have a different mode of action as the currently used anthelmintics. Many present studies confirmed the high efficacy of MOP against fourth larval and adult stages of Haemonchus contortus. The objective of this study was to determine in vitro efficacy of MOP against lower development stages (eggs, L 1 -L 3 larvae) and to compare it between resistant and susceptible isolates of H. contortus. For this purpose, two in vitro tests -egg hatch test and micro-agar larval development test were used. Results were quantified as 50 % lethal concentration (LC 50 ), 99 % lethal concentration (LC 99 ) and resistance factor (RF). This study revealed the high efficacy against lower larval stages (L 1 -L 3 ) of both resistant and susceptible strains of this parasite. Larval susceptibility was not dependent of the sensitivity status of the nematode isolate. On the other hand, ovicidal effect of MOP was very low.

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Dose confirmation studies for monepantel, an amino-acetonitrile derivative, against fourth stage gastro-intestinal nematode larvae infecting sheep

Cited by 34 publications

References 24 publications

A pooled analysis of the efficacy of monepantel, an amino-acetonitrile derivative against gastrointestinal nematodes of sheep

A pooled analysis of the efficacy of monepantel, an amino-acetonitrile derivative against gastrointestinal nematodes of sheep

The effect of sheep breed, age, and gender on the pharmacokinetics and efficacy of monepantel, an amino-acetonitrile derivative

Efficacy of monepantel against lower developmental stages of a multi-resistant and susceptible Haemonchus contortus isolates: an in vitro study

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