排序方式： 共有7条查询结果，搜索用时 15 毫秒
1
1.
Pharmacokinetic assessment of the monepantel plus oxfendazole combined administration in dairy cows 
下载免费PDF全文
下载免费PDF全文 M. Ballent P. Viviani F. Imperiale P. Dominguez S. Halwachs H. Mahnke W. Honscha C. Lanusse G. Virkel A. Lifschitz 《Journal of veterinary pharmacology and therapeutics》2018,41(2):292-300
Monepantel (MNP) is a novel anthelmintic compound launched into the veterinary pharmaceutical market. MNP is not licenced for use in dairy animals due to the prolonged elimination of its metabolite monepantel sulphone (MNPSO2) into milk. The goal of this study was to evaluate the presence of potential in vivo drug‐drug interactions affecting the pattern of milk excretion after the coadministration of the anthelmintics MNP and oxfendazole (OFZ) to lactating dairy cows. The concentrations of both parent drugs and their metabolites were measured in plasma and milk samples by HPLC. MNPSO2 was the main metabolite recovered from plasma and milk after oral administration of MNP. A high distribution of MNPSO2 into milk was observed. The milk‐to‐plasma ratio (M/P ratio) for this metabolite was equal to 6.75. Conversely, the M/P ratio of OFZ was 1.26. Plasma concentration profiles of MNP and MNPSO2 were not modified in the presence of OFZ. The pattern of MNPSO2 excretion into milk was also unchanged in animals receiving MNP plus OFZ. The percentage of the total administered dose recovered from milk was 0.09 ± 0.04% (MNP) and 2.79 ± 1.54% (MNPSO2) after the administration of MNP alone and 0.06 ± 0.04% (MNP) and 2.34 ± 1.38% (MNPSO2) after the combined treatment. The presence of MNP did not alter the plasma and milk disposition kinetics of OFZ. The concentrations of the metabolite fenbendazole sulphone tended to be slightly higher in the coadministered group. Although from a pharmacodynamic point of view the coadministration of MNP and OFZ may be a useful tool, the presence of OFZ did not modify the in vivo pharmacokinetic behaviour of MNP and therefore did not result in reduced milk concentrations of MNPSO2. 相似文献
2.
概述了一种新型氨基乙腈衍生物类驱虫药莫奈太尔的理化性质、作用机制、药代动力学、药效学等特点,以期为该药在兽医临床应用提供参考。 相似文献
3.
The recent registration in New Zealand of the first new class of broad-spectrum anthelmintic, for use against nematode parasites of ruminants, in nearly three decades has raised the possibility that parasite management practices could be improved to minimise the emergence of resistance to the new drug. A review of knowledge pertaining to the selection of anthelmintic resistance in nematode parasites of sheep highlights a number of management practices which could be altered to achieve this. A number of previously common practices such as whole-flock treatment of adult ewes around lambing, and treatment of lambs as they are moved onto pastures with low parasite contamination have been clearly identified as high risk for selecting resistant parasites. Once high-risk practices have been identified steps can be taken to either eliminate their use or mitigate the associated risk. Much of the focus on the management of resistance around the world is on the retention of susceptible genotypes in refugia. While approaches to retaining unselected parasites are likely to vary around the world, empirical studies indicate that the practice is likely to be effective at slowing the development of resistance. The challenge for farmers and advisors will be to strike a balance between retaining sufficient susceptible para-sites to usefully delay the development of resistance while not unduly compromising animal performance and farm profitability. The merits of combining different classes of anthelmintic in order to slow the development of resistance remains somewhat contentious in some countries. However, the attributes of oral anthelmintics are such that they seem likely to meet most, if not all, of the criteria for combinations to be highly effective at slowing the build-up of resistance in nematode parasites. It is evident that considerable progress has been made in understanding the factors involved in selecting anthelmintic-resistant nematodes since the last broad-spectrum anthelmintic class was released in the early 1980s. Therefore, it should be possible to manage a new class of anthelmintic in such a way as to significantly extend its effective life. The challenge is likely to be in convincing farmers of the merits of adopting such pro-active strategies. 相似文献
4.
Objective To evaluate the safety of monepantel and its major metabolite for dung fauna. Monepantel is a new oral anthelmintic drug for use in sheep at a dose of 2.5 mg active ingredient/kg body weight. Hazard (toxicity) is related to the expected exposure. Design The methodology was based on the Organisation for Economic Cooperation and Development (OECD) draft guideline for testing of chemicals, so dung from cattle, not sheep, and eggs of the dung fly, Scathophaga stercoraria and larvae of the dung beetle Aphodius constans were used. Procedures Monepantel or its sulfone metabolite were mixed into bovine faeces in which either dung fly eggs or dung beetle larvae were placed and their development observed. The primary endpoint was survival. Real exposure data (faecal concentrations) for comparison with the generated laboratory data were taken from a kinetics study in sheep dung. Results The no-observed effect concentration (NOEC) for monepantel was >1000 mg/kg substrate for dung flies and 250 mg/kg for dung beetles. The sulfone metabolite was slightly more toxic, with a NOEC of 500 mg/kg for dung flies and 125 mg/kg for dung beetles. Conclusion A comparison of the results to the maximum concentrations of 15 mg monepantel and 4.5 mg sulfone per kg dung observed under an exaggerated dosing regime in sheep indicates that monepantel poses no risk to insect dung fauna when used as recommended. The study is considered valid because representatives of both genera were able to develop in bovine or ovine dung. 相似文献
5.
BC Hosking TM Griffiths RG Woodgate RB Besier AS Le Feuvre P Nilon C Trengove KJ Vanhoff BG Kaye-Smith W Seewald 《Australian veterinary journal》2009,87(11):455-462
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. 相似文献
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. 相似文献
6.
Dobson RJ Hosking BC Besier RB Love S Larsen JW Rolfe PF Bailey JN 《Australian veterinary journal》2011,89(5):160-166
Objective To compare the risk of different treatment scenarios on selecting for anthelmintic resistance on Australian sheep farms. Design A computer simulation model predicted populations of Trichostrongylus colubriformis, Haemonchus contortus or Teladorsagia (Ostertagia) circumcincta, and the frequency of anthelmintic resistance genes. Method Nematode populations and the progression of drug resistance for a variety of treatment options and management practices in sheep‐rearing areas of Western Australia (WA), Victoria (VIC) and New South Wales (NSW) were simulated. A scoring system was devised to measure the success of each option in delaying resistance to each anthelmintic and in controlling nematode populations. Results The best option at all sites was combining the new anthelmintic (monepantel) with a triple mixture of benzimidazole, levamisole and abamectin (COM). The next best option was: in NSW, rotation at each treatment between monepantel, moxidectin and COM; in VIC, rotation at each treatment between monepantel and COM; and in WA, rotation at each treatment between monepantel (used in winter) and COM or moxidectin (used in summer–autumn). In WA, rapid selection for resistance occurred as a consequence of summer–autumn treatments; however, if a small percentage of adult stock were left untreated then this selection could be greatly reduced. Despite purposely assuming relatively high resistance to benzimidazole and levamisole, COM was still effective in controlling worms and delaying resistance. Conclusions Because of cost constraints, it may not be feasible or profitable for producers to always use the combination of all drugs. However, the second‐ and third‐best options still considerably slowed the development of anthelmintic resistance. 相似文献
7.
Dobson RJ Barnes EH Tyrrell KL Hosking BC Larsen JW Besier RB Love S Rolfe PF Bailey JN 《Australian veterinary journal》2011,89(6):200-208
Objective Develop a computer simulation model that uses daily meteorological data and farm management practices to predict populations of Trichostrongylus colubriformis, Haemonchus contortus and Teladorsagia (Ostertagia) circumcincta and the evolution of anthelmintic resistance within a sheep flock. Use the model to explore if increased refugia, provided by leaving some adult sheep untreated, would delay development of anthelmintic resistance without compromising nematode control. Procedures Compare model predictions with field observations from a breeding flock in Armidale, NSW. Simulate the impact of leaving 1–10% of adult sheep untreated in diverse sheep‐grazing systems. Results Predicted populations of Tr. colubriformis and T. circumcincta were less than those observed in the field, attributed to nutritional stress experienced by the sheep during drought and not accounted for by the model. Observed variation in faecal egg counts explained by the model (R2) for these species was 40–50%. The H. contortus populations and R2 were both low. Leaving some sheep untreated worked best in situations where animals were already grazing or were moved onto pastures with low populations of infective larvae. In those cases, anthelmintic resistance was delayed and nematode control was maintained when 1–4% of adult stock remained untreated. Conclusions In general, the model predicted that leaving more than 4% of adults untreated did not sufficiently delay the development of anthelmintic resistance to justify the increased production risk from such a strategy. The choice of a drug rotation strategy had an equal or larger effect on nematode control, and selection for resistance, than leaving 1–10% of adults untreated. 相似文献
1