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B.c. Hosking - One of the best experts on this subject based on the ideXlab platform.
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Effect of route of administration on the efficacy and pharmacokinetics of an experimental formulation of the amino-Acetonitrile Derivative monepantel in sheep.
Veterinary Record, 2010Co-Authors: B.c. Hosking, P A Stein, Wolfgang Seewald, Daniela Karadzovska, John K. House, Jerome M. GiraudelAbstract:The effect of the route of administration (oral, intraruminal and intra-abomasal) on the efficacy and pharmacokinetics of the new anthelmintic monepantel in sheep was investigated. The target nematodes were fourth-stage Haemonchus contortus, Teladorsagia circumcincta, Trichostrongylus colubriformis and Cooperia curticei. A clear difference in efficacy was identified between the routes of administration, although the difference did not consistently reach statistical significance; oral treatment was most effective, followed by intraruminal and then intra-abomasal administration. The same pattern was observed in the pharmacokinetic analysis, with lambs treated orally having more favourable exposure to monepantel and its sulfone metabolite (albeit in all but one instance not significantly different) than the lambs treated by the other routes of administration, which were very similar for most parameters.
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Quarantine treatment of sheep with monepantel--rapidity of fecal egg count reduction.
Veterinary Parasitology, 2010Co-Authors: Heinz Sager, G Strehlau, P.f. Rolfe, Brooke A. Allan, B.c. HoskingAbstract:In the presence of multiple anthelmintic resistance, effective quarantine treatment of sheep entering a farm has become a crucial tool in nematode management. In the present work, the use of the amino-Acetonitrile Derivative, monepantel as a quarantine treatment was investigated. Of special interest was the rapidity of decrease in fecal egg counts (FEC) compared to other anthelmintics used in sheep. In three different studies, sheep were either infected with Haemonchus contortus of known resistance status or with a panel of susceptible and multi-resistant gastro-intestinal nematodes. Fecal egg counts were determined from several hours up to 14 days after treatment with monepantel, benzimidazoles, levamisole, macrocyclic lactones or combinations of the latter three classes. The treatment of susceptible isolates with effective anthelmintics, either as single or combined applications caused a reduction of FEC to 0 within 3-4 days. The status of the resistant nematodes could be confirmed, as treatment with the affected classical anthelmintics never resulted in complete absence of parasite eggs in all samples analyzed. In the case of multi-resistant isolates, only monepantel was able to stop egg excretion, while all other treatments resulted in only a partial reduction of FEC. The resistance status of the nematodes did not influence the rapid decline of egg counts after treatment with monepantel.
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clinical field study to evaluate the efficacy and safety of the amino Acetonitrile Derivative monepantel compared with registered anthelmintics against gastrointestinal nematodes of sheep in australia
Australian Veterinary Journal, 2009Co-Authors: B.c. Hosking, T. M. Griffiths, Robert Woodgate, R.b. Besier, As Le Feuvre, P Nilon, C. L. Trengove, Kj Vanhoff, B G KayesmithAbstract:Objective To determine the efficacy of monepantel, a developmental compound from the amino-Acetonitrile Derivative class of anthelmintics, against field infections of gastrointestinal nematodes in sheep. Procedures Comparisons of efficacy (using standard faecal worm egg count reduction tests) and safety (on the basis of visual observations) were made in a large-scale field study in Australia, between groups of sheep treated with either an oral solution of monepantel or a registered anthelmintic. The sheep were naturally infected with the major gastrointestinal nematode genera present in Australia. Results The post-treatment efficacy results for monepantel were: at 7 days (+/-1 day) efficacy was >98%; at 14 days (+/-1 day) it was generally close to or >99%; and at 21 days (+/-1 day) efficacy was consistently >99%. A high proportion of the targeted nematode populations were confirmed as being resistant to one or more of the currently available anthelmintic classes. Conclusions Monepantel when used under field conditions at a minimum dose rate of 2.5 mg/kg was highly effective against mixed-genus natural field infections of the major gastrointestinal nematode genera including Haemonchus, Teladorsagia (Ostertagia), Trichostrongylus, Nematodirus, Chabertia and Oesophagostomum. This result included efficacy against some populations resistant to the currently available broad-spectrum anthelmintics. Few Cooperia spp. were present to allow confirmation of efficacy against this genus. On no occasion after treatment did any commercial anthelmintic-treated groups have significantly lower faecal egg counts than the monepantel-treated groups. Monepantel was safe for the target animals and human operators when used in a field situation.
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A large-scale clinical field study to evaluate the efficacy and safety of an oral formulation of the amino-Acetonitrile Derivative (AAD), monepantel, in sheep in New Zealand
New Zealand veterinary journal, 2009Co-Authors: P. C. Mason, Wolfgang Seewald, B.c. Hosking, T. M. Griffiths, B. G. Kaye-smith, R. M. Nottingham, D. J. W. Cole, Ch Mckay, B. ChamberlainAbstract:Abstract AIM: To evaluate the efficacy and safety of an oral formulation of the novel anthelmintic, monepantel (AAD 1566), in sheep, in comparison with some other anthelmintics currently registered in New Zealand. METHODS: A study was conducted on 18 farms located throughout the North and South Islands of New Zealand. On each farm, sheep naturally infected with the target nematodes were randomly assigned to groups, which were then treated with either monepantel, at a minimum dose rate of 2.5 mg/kg, or one of five other anthelmintics encompassing the range of single-entity and combination formulations that are commercially available in New Zealand, or left untreated as controls. Faecal samples were collected from all sheep pre-treatment (1–3 weeks before treatment), at the time of treatment, and approximately 1, 2 and 3 weeks after treatment (Days 7, 14 and 21). Faecal nematode egg counts (FEC) were measured in all samples, and the efficacy of treatments, as indicated by reductions in FEC, calculated. All ...
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Safety of an amino-Acetonitrile Derivative ( AAD ), monepantel, in weaned lambs following repeated oral administration.
New Zealand veterinary journal, 2009Co-Authors: N Malikides, B.c. Hosking, R Helbig, Roth, A Alexander, G StrehlauAbstract:Abstract AIM: To demonstrate the safety in weaned lambs of repetitive oral doses of monepantel, an amino-Acetonitrile Derivative (AAD), when administered at the proposed maximum recommended dose (MRD) and three and five times the MRD over 24 weeks. METHODS: A randomised controlled blinded study design was used. Fifty-six weaned lambs were randomly allocated into a control group, the MRD (3.75 mg/kg) and three (11.25 mg/ kg) and five (18.75 mg/kg) times the MRD treatment groups (n=7 castrated males plus seven females each). Treatment doses of monepantel were calculated based on the MRD of 3.75 mg/ kg, and administered orally on eight occasions at intervals of approximately 21 days. Detailed recording at multiple time points were made of veterinary examinations, observations for adverse events, bodyweight measurements, faecal scores, and haematology, clinical chemistry and coagulation variables. Gross pathology (including measurement of organ weights) and histopathology were performed at the completion of t...
Heinz Sager - One of the best experts on this subject based on the ideXlab platform.
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Quarantine treatment of sheep with monepantel--rapidity of fecal egg count reduction.
Veterinary Parasitology, 2010Co-Authors: Heinz Sager, G Strehlau, P.f. Rolfe, Brooke A. Allan, B.c. HoskingAbstract:In the presence of multiple anthelmintic resistance, effective quarantine treatment of sheep entering a farm has become a crucial tool in nematode management. In the present work, the use of the amino-Acetonitrile Derivative, monepantel as a quarantine treatment was investigated. Of special interest was the rapidity of decrease in fecal egg counts (FEC) compared to other anthelmintics used in sheep. In three different studies, sheep were either infected with Haemonchus contortus of known resistance status or with a panel of susceptible and multi-resistant gastro-intestinal nematodes. Fecal egg counts were determined from several hours up to 14 days after treatment with monepantel, benzimidazoles, levamisole, macrocyclic lactones or combinations of the latter three classes. The treatment of susceptible isolates with effective anthelmintics, either as single or combined applications caused a reduction of FEC to 0 within 3-4 days. The status of the resistant nematodes could be confirmed, as treatment with the affected classical anthelmintics never resulted in complete absence of parasite eggs in all samples analyzed. In the case of multi-resistant isolates, only monepantel was able to stop egg excretion, while all other treatments resulted in only a partial reduction of FEC. The resistance status of the nematodes did not influence the rapid decline of egg counts after treatment with monepantel.
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The effect of sheep breed, age, and gender on the pharmacokinetics and efficacy of monepantel, an amino-Acetonitrile Derivative
Parasitology Research, 2009Co-Authors: Barry C. Hosking, Heinz Sager, Wolfgang Seewald, Daniela Karadzovska, Jerome M. Giraudel, Jozef VercruysseAbstract: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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A pooled analysis of the efficacy of monepantel, an amino-Acetonitrile Derivative against gastrointestinal nematodes of sheep
Parasitology Research, 2009Co-Authors: Barry C. Hosking, Heinz Sager, Peter F. Rolfe, Wolfgang SeewaldAbstract: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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Efficacy of the amino-Acetonitrile Derivative, monepantel, against experimental and natural adult stage gastro-intestinal nematode infections in sheep.
Veterinary parasitology, 2008Co-Authors: Heinz Sager, P A Stein, B.c. Hosking, Beatrice Bapst, Kathleen VanhoffAbstract:Abstract Multiple drug resistance by nematodes, against anthelmintics has become an important economic problem in sheep farming worldwide. Here we describe the efficacy of monepantel, a developmental molecule from the recently discovered anthelmintic class, the amino-Acetonitrile Derivatives (AADs). Efficacy was tested against adult stage gastro-intestinal nematodes (GINs) in experimentally and naturally infected sheep at a dose of 2.5 mg/kg body weight when administered as an oral solution. Some of the isolates used in experimental infection studies were known to be resistant to the benzimidazoles or levamisole anthelmintics; strains resistant to the macrocyclic lactones were not available for these tests. Worm count-based efficacies of >98% were determined in these studies. As an exception, Oesophagostomum venulosum was only reduced by 88% in one study, albeit with a low worm burden in the untreated controls (geometric mean 15.4 worms). Similar efficacies for monepantel were also confirmed in naturally infected sheep. While the efficacy against most species was >99%, the least susceptible species was identified as Nematodirus spathiger, and although efficacy was 92.4% in one study it was generally >99%. Several animals were infected with Trichuris ovis, which was not eliminated after the treatment. Monepantel demonstrated high activity against a broad range of the important GINs of sheep, which makes this molecule an interesting candidate for use in this species, particularly in regions with problems of anthelmintic resistance. Monepantel was well tolerated by the treated sheep, with no treatment related adverse events documented.
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Dose confirmation studies for monepantel, an amino-Acetonitrile Derivative, against fourth stage gastro-intestinal nematode larvae infecting sheep.
Veterinary Parasitology, 2008Co-Authors: B.c. Hosking, P A Stein, Wolfgang Seewald, D Mosimann, G Strehlau, R Kaminsky, D.p. Dobson, Beatrice Bapst, P. C. Mason, Heinz SagerAbstract:Monepantel is the first compound from the recently discovered amino-Acetonitrile Derivative (AAD) class of anthelmintics to be developed for use in sheep. Three dose determination studies were conducted in Australia and Switzerland to identify the minimum therapeutic dose of monepantel when formulated for the oral treatment of sheep to control fourth stage (L4) gastro-intestinal nematode larvae. In each study, sheep infected with the target nematodes (selected from Haemonchus contortus, Teladorsagia (Ostertagia) circumcincta, Teladorsagia trifurcata, Trichostrongylus axei, Trichostrongylus colubriformis, Trichostrongylus vitrinus, Cooperia curticei, Cooperia oncophora, Nematodirus battus, Nematodirus filicollis, Nematodirus spathiger, Chabertia ovina and Oesophagostomum venulosum) were treated with either 1.25, 2.5 or 5.0 mg monepantel/kg liveweight. Following euthanasia and worm counting, efficacy was calculated against worm counts from untreated control groups. Monepantel proved highly effective at 2.5 and 5.0 mg/kg, but was only moderately effective against some nematode species (L4 stage) at 1.25 mg/kg. The results also confirmed that monepantel will effectively control L4 stages of nematodes resistant to at least some of the currently available broad-spectrum anthelmintic classes (macrocyclic lactone resistant strains were not included in the studies). It was concluded that 2.5 mg/kg would be a suitable minimum dose rate for a commercial product. No adverse events related to treatment with monepantel were detected.
Wolfgang Seewald - One of the best experts on this subject based on the ideXlab platform.
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Effect of route of administration on the efficacy and pharmacokinetics of an experimental formulation of the amino-Acetonitrile Derivative monepantel in sheep.
Veterinary Record, 2010Co-Authors: B.c. Hosking, P A Stein, Wolfgang Seewald, Daniela Karadzovska, John K. House, Jerome M. GiraudelAbstract:The effect of the route of administration (oral, intraruminal and intra-abomasal) on the efficacy and pharmacokinetics of the new anthelmintic monepantel in sheep was investigated. The target nematodes were fourth-stage Haemonchus contortus, Teladorsagia circumcincta, Trichostrongylus colubriformis and Cooperia curticei. A clear difference in efficacy was identified between the routes of administration, although the difference did not consistently reach statistical significance; oral treatment was most effective, followed by intraruminal and then intra-abomasal administration. The same pattern was observed in the pharmacokinetic analysis, with lambs treated orally having more favourable exposure to monepantel and its sulfone metabolite (albeit in all but one instance not significantly different) than the lambs treated by the other routes of administration, which were very similar for most parameters.
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The effect of sheep breed, age, and gender on the pharmacokinetics and efficacy of monepantel, an amino-Acetonitrile Derivative
Parasitology Research, 2009Co-Authors: Barry C. Hosking, Heinz Sager, Wolfgang Seewald, Daniela Karadzovska, Jerome M. Giraudel, Jozef VercruysseAbstract: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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A pooled analysis of the efficacy of monepantel, an amino-Acetonitrile Derivative against gastrointestinal nematodes of sheep
Parasitology Research, 2009Co-Authors: Barry C. Hosking, Heinz Sager, Peter F. Rolfe, Wolfgang SeewaldAbstract: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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Pharmacokinetics of monepantel and its sulfone metabolite, monepantel sulfone, after intravenous and oral administration in sheep.
Journal of Veterinary Pharmacology and Therapeutics, 2009Co-Authors: Daniela Karadzovska, Wolfgang Seewald, A. Browning, M. Smal, J. Bouvier, Jerome M. GiraudelAbstract:: The pharmacokinetic properties of the developmental Amino-Acetonitrile Derivative (AAD), monepantel and its sulfone metabolite, monepantel sulfone were investigated in sheep following intravenous (i.v.) and oral administrations. The sulfone metabolite was rapidly formed and predominated over monepantel 4 h after dosing, irrespective of the route of administration. The steady-state volume of distribution, total body clearance and mean residence time of monepantel were 7.4 L/kg, 1.49 L/(kg x h) and 4.9 h, respectively and 31.2 L/kg, 0.28 L/(kg x h) and 111 h, respectively for monepantel sulfone. The overall bioavailability of monepantel was 31%, but it was demonstrated that approximately the same amount of monepantel sulfone was produced whether monepantel was given intravenously or orally (AUC((0-infinity)) oral/AUC((0-infinity)) i.v. of 94% for monepantel sulfone), making oral administration a very efficient route of administration for monepantel in terms of the amount of sulfone metabolite generated. Because monepantel sulfone is the main chemical entity present in sheep blood after monepantel administration and because it is also an active metabolite, its pharmacokinetic properties are of primary importance for the interpretation of future residue and efficacy studies. Overall, these pharmacokinetic data aid in the evaluation of monepantel as an oral anthelmintic in sheep.
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A large-scale clinical field study to evaluate the efficacy and safety of an oral formulation of the amino-Acetonitrile Derivative (AAD), monepantel, in sheep in New Zealand
New Zealand veterinary journal, 2009Co-Authors: P. C. Mason, Wolfgang Seewald, B.c. Hosking, T. M. Griffiths, B. G. Kaye-smith, R. M. Nottingham, D. J. W. Cole, Ch Mckay, B. ChamberlainAbstract:Abstract AIM: To evaluate the efficacy and safety of an oral formulation of the novel anthelmintic, monepantel (AAD 1566), in sheep, in comparison with some other anthelmintics currently registered in New Zealand. METHODS: A study was conducted on 18 farms located throughout the North and South Islands of New Zealand. On each farm, sheep naturally infected with the target nematodes were randomly assigned to groups, which were then treated with either monepantel, at a minimum dose rate of 2.5 mg/kg, or one of five other anthelmintics encompassing the range of single-entity and combination formulations that are commercially available in New Zealand, or left untreated as controls. Faecal samples were collected from all sheep pre-treatment (1–3 weeks before treatment), at the time of treatment, and approximately 1, 2 and 3 weeks after treatment (Days 7, 14 and 21). Faecal nematode egg counts (FEC) were measured in all samples, and the efficacy of treatments, as indicated by reductions in FEC, calculated. All ...
G Strehlau - One of the best experts on this subject based on the ideXlab platform.
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Quarantine treatment of sheep with monepantel--rapidity of fecal egg count reduction.
Veterinary Parasitology, 2010Co-Authors: Heinz Sager, G Strehlau, P.f. Rolfe, Brooke A. Allan, B.c. HoskingAbstract:In the presence of multiple anthelmintic resistance, effective quarantine treatment of sheep entering a farm has become a crucial tool in nematode management. In the present work, the use of the amino-Acetonitrile Derivative, monepantel as a quarantine treatment was investigated. Of special interest was the rapidity of decrease in fecal egg counts (FEC) compared to other anthelmintics used in sheep. In three different studies, sheep were either infected with Haemonchus contortus of known resistance status or with a panel of susceptible and multi-resistant gastro-intestinal nematodes. Fecal egg counts were determined from several hours up to 14 days after treatment with monepantel, benzimidazoles, levamisole, macrocyclic lactones or combinations of the latter three classes. The treatment of susceptible isolates with effective anthelmintics, either as single or combined applications caused a reduction of FEC to 0 within 3-4 days. The status of the resistant nematodes could be confirmed, as treatment with the affected classical anthelmintics never resulted in complete absence of parasite eggs in all samples analyzed. In the case of multi-resistant isolates, only monepantel was able to stop egg excretion, while all other treatments resulted in only a partial reduction of FEC. The resistance status of the nematodes did not influence the rapid decline of egg counts after treatment with monepantel.
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Reproductive safety of an amino-Acetonitrile Derivative (AAD), monepantel, in rams following repeated oral administration
New Zealand veterinary journal, 2009Co-Authors: N Malikides, R Helbig, R Mahoney, B George, K Baker, K Vanhoff, K Spencer, C.a. Hall, R Debenedetti, G StrehlauAbstract:Abstract AIM: To demonstrate the clinical and reproductive safety in rams of repetitive oral doses of monepantel, an amino-Acetonitrile Derivative (AAD), when administered at three times the proposed maximum recommended dose (MRD) over an entire spermatogenic cycle and during mating with ewes. METHODS: A randomised controlled blinded study design was used with 28 rams randomly divided into two groups. The control group was treated with saline, and the other group was given three times the MRD (11.25 mg/kg) of monepantel. Treatments were administered orally every 5 days, for 100 days, during an entire spermatogenic cycle and subsequent mating period. Detailed recording at multiple time points were made of veterinary examinations; observations for adverse events; bodyweight measurements; faecal scores; haematology, clinical chemistry and coagulation variables; semen indices; evaluation of serving capacity; and gross pathology (including measurement of organ weights) performed on 10 rams from each group at t...
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Safety of an amino-Acetonitrile Derivative (AAD), monepantel, in ewes and their offspring following repeated oral administration
New Zealand veterinary journal, 2009Co-Authors: N Malikides, R Mahoney, K Baker, K Vanhoff, K Spencer, C.a. Hall, R Debenedetti, G StrehlauAbstract:Abstract AIM: To demonstrate the clinical and reproductive safety in ewes and their offspring of repetitive oral doses of monepantel, an amino-Acetonitrile Derivative (AAD), when administered at three times the proposed maximum recommended dose (MRD) over an entire reproductive cycle. METHODS: A randomised controlled blinded study design was used. One hundred and twelve primi- or multi-parous ewes and 28 rams were randomly allocated into control and treated groups (n=56 for groups of ewes, n=14 for groups of rams). Two control ewes and two treated ewes were randomly selected to form 28 subgroups. A control or treated ram was then randomly allocated to each subgroup, to form control ram/treated ewe, control ram/control ewe, treated ram/treated ewe, and treated ram/control ewe ‘treatment/mating’ units. Control animals were treated with saline, and treated animals given three times the MRD (11.25 mg/kg) of monepantel. Treatments were administered orally every 5 days during an entire reproductive cycle, inclu...
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Safety of an amino-Acetonitrile Derivative ( AAD ), monepantel, in weaned lambs following repeated oral administration.
New Zealand veterinary journal, 2009Co-Authors: N Malikides, B.c. Hosking, R Helbig, Roth, A Alexander, G StrehlauAbstract:Abstract AIM: To demonstrate the safety in weaned lambs of repetitive oral doses of monepantel, an amino-Acetonitrile Derivative (AAD), when administered at the proposed maximum recommended dose (MRD) and three and five times the MRD over 24 weeks. METHODS: A randomised controlled blinded study design was used. Fifty-six weaned lambs were randomly allocated into a control group, the MRD (3.75 mg/kg) and three (11.25 mg/ kg) and five (18.75 mg/kg) times the MRD treatment groups (n=7 castrated males plus seven females each). Treatment doses of monepantel were calculated based on the MRD of 3.75 mg/ kg, and administered orally on eight occasions at intervals of approximately 21 days. Detailed recording at multiple time points were made of veterinary examinations, observations for adverse events, bodyweight measurements, faecal scores, and haematology, clinical chemistry and coagulation variables. Gross pathology (including measurement of organ weights) and histopathology were performed at the completion of t...
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Dose confirmation studies for monepantel, an amino-Acetonitrile Derivative, against fourth stage gastro-intestinal nematode larvae infecting sheep.
Veterinary Parasitology, 2008Co-Authors: B.c. Hosking, P A Stein, Wolfgang Seewald, D Mosimann, G Strehlau, R Kaminsky, D.p. Dobson, Beatrice Bapst, P. C. Mason, Heinz SagerAbstract:Monepantel is the first compound from the recently discovered amino-Acetonitrile Derivative (AAD) class of anthelmintics to be developed for use in sheep. Three dose determination studies were conducted in Australia and Switzerland to identify the minimum therapeutic dose of monepantel when formulated for the oral treatment of sheep to control fourth stage (L4) gastro-intestinal nematode larvae. In each study, sheep infected with the target nematodes (selected from Haemonchus contortus, Teladorsagia (Ostertagia) circumcincta, Teladorsagia trifurcata, Trichostrongylus axei, Trichostrongylus colubriformis, Trichostrongylus vitrinus, Cooperia curticei, Cooperia oncophora, Nematodirus battus, Nematodirus filicollis, Nematodirus spathiger, Chabertia ovina and Oesophagostomum venulosum) were treated with either 1.25, 2.5 or 5.0 mg monepantel/kg liveweight. Following euthanasia and worm counting, efficacy was calculated against worm counts from untreated control groups. Monepantel proved highly effective at 2.5 and 5.0 mg/kg, but was only moderately effective against some nematode species (L4 stage) at 1.25 mg/kg. The results also confirmed that monepantel will effectively control L4 stages of nematodes resistant to at least some of the currently available broad-spectrum anthelmintic classes (macrocyclic lactone resistant strains were not included in the studies). It was concluded that 2.5 mg/kg would be a suitable minimum dose rate for a commercial product. No adverse events related to treatment with monepantel were detected.
Barry C. Hosking - One of the best experts on this subject based on the ideXlab platform.
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The efficacy of monepantel, an amino-Acetonitrile Derivative, against gastrointestinal nematodes of sheep in three countries of southern Latin America
Parasitology Research, 2009Co-Authors: Miguel Bustamante, Pedro E. Steffan, Jorge Bonino Morlán, Flavio Echevarria, César A. Fiel, Herculano Cardozo, Daniel Castells, Barry C. HoskingAbstract:The efficacy of the novel anthelmintic, monepantel (an amino-Acetonitrile Derivative), was investigated in sheep naturally infected with gastrointestinal nematodes in five studies in Argentina, Brazil, and Uruguay. Monepantel, administered at 2.5 mg/kg liveweight, was highly effective (>99.7%) against Haemonchus contortus , Teladorsagia ( Ostertagia ) circumcincta , Trichostrongylus axei , Trichostrongylus c olubriformis , Cooperia curticei , Cooperia mcmasteri , Cooperia oncophora , Cooperia pectinata , Cooperia punctata , and Nematodirus spathiger , including strains resistant to the older broad-spectrum anthelmintics. Efficacy against C. mcmasteri , C. pectinata , and C. punctata is documented for the first time. The treatment with monepantel was well tolerated by the sheep.
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The effect of sheep breed, age, and gender on the pharmacokinetics and efficacy of monepantel, an amino-Acetonitrile Derivative
Parasitology Research, 2009Co-Authors: Barry C. Hosking, Heinz Sager, Wolfgang Seewald, Daniela Karadzovska, Jerome M. Giraudel, Jozef VercruysseAbstract: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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A pooled analysis of the efficacy of monepantel, an amino-Acetonitrile Derivative against gastrointestinal nematodes of sheep
Parasitology Research, 2009Co-Authors: Barry C. Hosking, Heinz Sager, Peter F. Rolfe, Wolfgang SeewaldAbstract: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.