乙酰氨基阿维菌素国家对照品的研制

以乙酰氨基阿维菌素为原料研制首批乙酰氨基阿维菌素国家对照品,并进行质量评价。采用高效液相色谱法和质谱法对原料进行结构确证,分装后的乙酰氨基阿维菌素对照品采用质量平衡法定值,同时采用高效液相色谱外标法加以佐证。结果显示,以质量平衡法计算乙酰氨基阿维菌素(B_1a+B_1b)含量为97.79%,液相色谱外标法测定含量为98.18%,两种方法测定结果基本一致。本次研制的乙酰氨基阿维菌素对照品可用于乙酰氨基阿维菌素及其制剂的鉴别与含量测定。     

The environmental safety of eprinomectin to earthworms

A study was conducted to assess the environmental safety of the endectocide eprinomectin to the earthworm Lumbricus terrestris under conditions mimicking typical product use on pasture. The LC50 value of eprinomectin in artificial soil after 28 days of exposure is higher than the levels expected in feces from dosed cattle or in soil fertilized with manure from dosed cattle, which indicates a wide margin of safety for this compound to earthworms. However, the no-observed-effect concentration has not been established. Therefore, the current study was conducted to determine whether there would be any effects on earthworms from feces from cattle treated with the commercial formulation of eprinomectin. Feces were collected rectally from grazing cattle on Day 0 before treatment and on Days 2, 4, 7 and 14 after treatment with EPRINEX (eprinomectin) Pour-On for Beef and Dairy Cattle (Merial Limited) at 0.5 mg eprinomectin per kg bodyweight. Assays of eprinomectin B1a (the major component of eprinomectin) were 0, 0.427, 0.152, 0.0512 and 0.00185 mg kg-1 wet weight of feces (equivalent to 0, 3.34, 1.19, 0.40 and 0.010 mg kg-1 on a dry weight basis, respectively). No significant differences (p>0.05) were observed at any day post-treatment in the survival or behavioral effects of any worms fed post-dose feces relative to the worms fed control feces. All post-dose comparisons of weight changes of living earthworms to the control group were not significantly different (p>0.05), indicating that treatment of cattle with EPRINEX (eprinomectin) Pour-On for Beef and Dairy Cattle did not affect feeding or weight gain of the earthworms. The LC50 value and the results of this study establish the wide margin of safety afforded to earthworms by eprinomectin under typical usage conditions.     

埃普利诺菌素浇泼剂对牦牛皮蝇幼虫驱除效果试验

应用埃普利诺菌素浇泼剂驱除牦牛皮蝇幼虫,并设埃普利诺菌素注射剂药物对照组和阳性对照组。结果：剖检埃普利诺菌素浇泼剂300μg/kg,400μg/kg,500μg/kg剂量组牦牛与药物对照埃普利诺菌素注射剂组及伊维菌素浇泼剂组牦牛,均未检出皮蝇1期幼虫,而阳性对照组牦牛皮蝇1期幼虫感染率35.0%,平均感染强度29.4（9～53）条。翌年3、5月份两次触摸检查牛背部皮下瘤疤和皮肤虫孔,4个药物试验组牦牛均未检出,而阳性对照组牦牛两次检查平均感染率45.16%,平均感染强度6.45个。试验证明埃普利诺菌素浇泼剂低、中、高3个剂量对寄生于牦牛的皮蝇幼虫驱净率、驱虫率均达100.0%,高效安全。     

Pharmacokinetics of Eprinomectin in Plasma and Milk following Subcutaneous Administration to Lactating Dairy Cattle

Eprinomectin is only available as a topically applied anthelmintic for dairy cattle. To determine whether eprinomectin can be applied as an injectable formulation in dairy cattle, a novel injectable formulation was developed and was subcutaneously delivered to four lactating dairy cattle at a dose rate of 0.2 mg/ kg. Plasma and milk samples were collected. The concentrations of eprinomectin in all samples were determined by HPLC. The peak plasma concentration (C_max)of 44.0±24.2 ng/ml occurred 39±19.3 h after subcutaneous administration, equivalent to the C_max (43.76±18.23 ng/ml) previously reported for dairy cattle after a pour-on administration of 0.5 mg/kg eprinomectin. The area under the plasma concentration–time curve (AUC) after subcutaneous administration was 7354±1861 (ng h)/ml, higher than that obtained after pour-on delivery (5737.68±412.80 (ng h)/ml). The mean residence time (MRT) of the drug in plasma was 211±55.2 h. Eprinomectin was detected in the milk at the second sampling time. The concentration of drug in milk was parallel to that in plasma, with a milk to plasma ratio of 0.16±0.01. The highest detected concentration of eprinomectin in milk was 9.0 ng/ml, below the maximum residue limit (MRL) of eprinomectin in milk established by the Joint FAO/WHO Expert Committee on Food Additives in 2000. The amount of eprinomectin recovered in the milk during this trial was 0.39%±0.08% of the total administered dose. This study demonstrates that subcutaneous administration of eprinomectin led to higher bioavailability and a lower dose than a pour-on application, and that an injectable formulation of eprinomectin may be applied in dairy cattle with a zero withdrawal period.     

Failure of ivermectin and eprinomectin to control Amblyomma parvum in goats: characterization of acaricidal activity and drug pharmacokinetic disposition

The therapeutic efficacies of ivermectin (subcutaneous injection) and eprinomectin (topical treatment) given at two different dosage levels to goats naturally infested with Amblyomma parvum were assessed. Treatments included subcutaneous injection of ivermectin at 0.2 and 0.4mg/kg and extra-label pour-on administration of eprinomectin at 0.5 and 1mg/kgb.w. Ivermectin and eprinomectin failed to control Amblyomma parvum on goats. Treatment with ivermectin resulted in a low number of engorged female ticks in relation to untreated control goats and, at the highest dose rate (0.4mg/kg), the female engorgement weights were significantly lower and the pre-oviposition period significantly longer than those observed in ticks recovered from untreated control goats. The tick efficacy assessment was complemented in a separate group of tick-free goats with a pharmacokinetic characterization of eprinomectin (topically administered at 0.5, 1.0 and 1.5mg/kg) and ivermectin (subcutaneous treatment given at (0.2 and 0.4mg/kg) in goats. Heparinized blood samples were taken between 0 and 21 days post-treatment. Higher and more persistent drug plasma concentrations were recovered after the subcutaneous treatment with ivermectin compared to those obtained for eprinomectin topically administered. The understanding of the relationship among the pattern of drug absorption, the kinetic disposition and the resultant clinical efficacy is relevant to improve the poor performance observed for ivermectin and eprinomectin against A. parvum on goats.     

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.     

Plasma kinetics,excretion in milk of eprinomectin,and its efficacy against Hypoderma spp. following topical administration in yaks

The plasma pharmacokinetics and mammary excretion of eprinomectin were determined in dairy yaks following topical administration at a dose of 0.5 mg/kg. The kinetics of plasma and milk concentrations were analyzed using a noncompartmental model. Plasma and milk concentrations of eprinomectin increased to reach maximal concentrations of 5.45 ± 2.84 and 2.29 ± 0.90 ng/mL at a T_max of 1.79 ± 0.57 and 2.00 ± 0.82 days, respectively. The concentration of eprinomectin in plasma was remained >0.5 ng/mL for more than 30 days after administration. The mean residence times of eprinomectin in plasma and milk were 14.73 ± 6.22 and 9.37 ± 2.81 days, respectively. The AUC value in plasma (55.89 ± 18.16 ng day/mL) was threefold greater than that in milk (18.02 ± 6.48 ng day/mL). The AUC milk/plasma ratio was 0.33 ± 0.08. The systemic availability of eprinomectin in yaks was lower than that observed value in other domestic bovines. The low level of eprinomectin excretion in milk suggests that eprinomectin can be used in yaks with zero milk‐withdrawal time. The efficacy of eprinomectin against naturally acquired larvae of Hypoderma spp. was also determined in yaks. Topically administrated eprinomectin at a dose of 0.5 mg/kg was 100% efficacious against larvae of Hypoderma bovis, H. lineatum, and H. sinense.     

Some Pharmacokinetic Parameters of Eprinomectin in Goats following Pour-on Administration

Some pharmacokinetic parameters of eprinomectin were determined in goats following topical application at a dose rate of 0.5 mg/kg. The plasma concentration versus time data for the drug were analysed using a one-compartment model. The maximum plasma concentration of 5.60±1.01 ng/ml occurred 2.55 days after administration. The area under the concentration–time curve (AUC) was 72.31±11.15 ng day/ml and the mean residence time (MRT) was 9.42±0.43 days. Thus, the systemic availability of eprinomectin to goats was significantly lower than that for cows. The low concentration of eprinomectin in the plasma of goats suggests that the pour-on dose of 0.5 mg/kg would be less effective in this species than in cows. Further relevant information about the optimal dosage and residues in the milk of dairy goats is needed before eprinomectin should be used in this species.     

Eprinomectin treatment of psoroptic mange in hunter/jumper and dressage horses: a prospective, randomized, double-blinded, placebo-controlled clinical trial

The purpose of this prospective, double-blinded, placebo-controlled clinical trial was to investigate the efficacy of topical eprinomectin for the treatment of psoroptic mange infestation in horses. 24 privately owned hunter/jumper and dressage horses were diagnosed with psoroptic mange infestation based on physical findings and skin scraping results were enrolled and randomly assigned to either topical eprinomectin pour-on solution (at a dose of 500mug/kg body weight weekly once for four applications) treatment group or a placebo group (purified water). Clinical evaluations and skin scrapings were done by the same veterinary investigator at the beginning, during and at the end of the treatment. Both owners and veterinary investigator were blinded to the allocation to the groups. The efficacy of eprinomectin was assessed both clinically and parasitologically by the presence or absence of viable mites. Horses were scraped for psoroptic mites on days 7, 14, 21, 28 and 40 for follow-up. Fisher's exact test was used to assess differences between the eprinomectin treatment and placebo in the number of horses without mites (cure rates) on each assessment date. It was found that significantly fewer eprinomectin treated horses had P. equi mites detected on skin scrapings (p<0.01) than the placebo group. In conclusion, eprinomectin was effective and safe therapy against natural infestations of P. equi in the horses included in this study.     

Efficacy of an injectable formulation of eprinomectin against Psoroptes cuniculi, the ear mange mite in rabbits

Thirty rabbits naturally infected with ear mange mite, Psoroptes cuniculi, were subcutaneously administrated with a single dose of eprinomectin at 100, 200 and 300 microg/kg body weight or vehicle on day 0. The extent of lesions was scored on day -6 (prior to treatment), day 0 (treated), days 7, 14, 21, 28 and 35, the ear scabs were collected simultaneously; mites in scabs were examined and counted. The results showed that a single dose of eprinomectin at 200 or 300 microg/kg body weight following subcutaneous administration was able to eliminate P. cuniculi infection in rabbits, and a dose of eprinomectin at 100 microg/kg could significantly reduce mites but was unable to eliminate P. cuniculi.     

Efficacy of topical administration of eprinomectin for treatment of ear mite infestation in six rabbits

Six rabbits naturally infested with Psoroptes cuniculi were treated topically on the skin at the base of the neck with 0.5 mg kg(-1) of 0.5% pour-on eprinomectin for cattle, twice at 14-day intervals. Efficacy of the drug was based on the disappearance of clinical signs and the absence of live mites for a period of 6 weeks. Clinical improvement was seen within 3 days of the first application; however, complete recovery of clinical signs and elimination of mites in 5/6 rabbits did not occur until the end of the study. No adverse reactions attributable to eprinomectin treatment were observed during the observation period. Results of this trial indicated that eprinomectin was partially effective in the treatment of psoroptic mange in rabbits.     

Field efficacy of minidosed eprinomectin against Hypoderma spp. in dairy cattle

A chemoprophylactic field trial was conducted to assess the efficacy of pour-on eprinomectin applied at the approximate dose of 50 mcg/kg to dairy cattle with naturally occurring hypodermosis. Two-hundred-eleven cattle, selected from two herds with a high prevalence of Hypoderma spp. infestation, were divided in three groups: Group A (N = 71) was treated with pour-on eprinomectin at the recommended dosage of 500 mcg/kg, Group B (N = 64) at the lower dose of 50 mcg/kg, a third group (Group C, N = 76) served as untreated control group. Treatments were performed in November-December 2002 and the animals were examined for the presence of warbles in the following April and June. No larvae emerged in the treated groups, whereas a variable number of warbles (ranging from 1 to 28) were found in control animals. Adverse reactions were not observed in any animal, and only minor side effects were observed. A larger field trial carried out in the following year (1064 treated and 131 untreated control cattle) confirmed the chemoprophylactic efficacy of minidosed eprinomectin against Hypoderma spp. Administration of eprinomectin minidoses in dairy cattle is interesting because of the low costs involved and no need for milk withdrawal.     

Field trials in New Zealand confirming the efficacy of eprinomectin applied topically to cattle

The efficacy and acceptability of eprinomectin in a topical formulation against gastro-intestinal nematodes in cattle was assessed under field conditions. Seven similar commercial dairy farms in the North and South Islands of New Zealand were included in the studies, involving 247 Holstein-Friesian, Jersey or Jersey-cross cattle. Cattle were confirmed by positive faecal nematode egg counts to have natural infections of gastro-intestinal nematodes and were held in separate treatment groups. In each replicate, four animals received eprinomectin (500 microg/kg body weight) and one animal received vehicle solution, all applied topically at 1 ml/10 kg body weight. Faecal samples were collected before, and 14 days after treatment, for faecal trongylid egg counts. Animals treated with eprinomectin had significantly lower (p < 0.05) Day 14 faecal strongylid egg counts than the controls. There were no significant differences (p > 0.10) between treated and control groups for pretreatment strongylid egg counts. No formulation runoff or adverse reactions were observed. These studies showed eprinomectin to be effective against gastro-intestinal nematode infections and safe for use in dairy cattle under natural field conditions.     

Field studies investigating anthelmintic resistance in young cattle on five farms in New Zealand

AIM: To investigate the efficacy of pour-on anthelmintics against field strains of parasitic nematodes in young cattle on five farms in New Zealand. METHODS: Faecal nematode egg count (FEC) reduction (FECR) tests were carried out on five calf-rearing farms using pour-on formulations of levamisole, ivermectin, eprinomectin, and the simultaneous administration of levamisole and ivermectin. Faecal samples were collected per rectum before treatment and about 7, 14, 21 and 28 days after treatment, for FEC and faecal nematode larval culture. RESULTS: Resistance (i.e. <95% reduction in FEC) of Cooperia oncophora to ivermectin and eprinomectin was identified on all five farms. There was limited evidence of possible emerging resistance in Ostertagia spp to ivermectin but not eprinomectin, in short-tailed larvae of Cooperia spp to ivermectin and eprinomectin, and in Trichostrongylus spp to ivermectin, eprinomectin and levamisole used separately. Levamisole was effective against C. oncophora, but had variable efficacy against Ostertagia spp in the calves in this study. Simultaneous treatment with levamisole and ivermectin pour-on formulations were effective against all genera on all farms. CONCLUSIONS: To effectively manage roundworm parasites in their calves farmers need to be aware of the resistance status of the parasites on their farms. Levamisole is likely to be an effective anthelmintic on most farms at times of the year when the impact of Ostertagia spp is not high. Simultaneous administration of levamisole and ivermectin pour-on anthelmintics to cattle is likely to control both ML-resistant C. oncophora and stages of Ostertagia spp that are not controlled by levamisole alone.     

乙酰氨基阿维菌素乳剂HPLC含量检测方法的建立

[目的]建立高效液相色谱法测定乙酰氨基阿维菌素乳剂含量的方法。[方法]采用C18（150×4．6mm,5μm）色谱柱,以乙腈-水（70：30）为流动相,流速为1．0mL/min,检测波长为245nm,进样量为20μL,柱温为25℃。[结果]乙酰氨基阿维菌素在0．1～20μg/mL浓度范围内呈现良好的线性关系,标准曲线方程为C=1．6015A-0．00206,r=1．000（n=5）,该方法的RSD在0．72％～1．40％,平均回收率在96．5％～100．5％。[结论]该方法灵敏度高、准确度高、重现性好、简便快速,可用于乙酰氨基阿维菌素乳剂和其他剂型的质量控制。     

An evaluation of the quality and physical properties of calf leather following topical application of eprinomectin

The gross and histological appearance of skins obtained from twelve 6-10 month-old Friesian X Hereford calves 14-15 days after they were treated with a topical formulation of 0.5% eprinomectin administered at 1 ml per 10 kg bodyweight was compared to that of skins from twelve untreated controls. No significant differences were observed and there were also no significant differences in the quality and physical properties of leather produced from the skins of treated and untreated groups, indicating that topical eprinomectin has no deleterious effects on the leather quality of calf skins.     

A comparison of the development and survival of the dung beetle, Onthophagus taurus (Schreb.) when fed on the faeces of cattle treated with pour-on formulations of eprinomectin or moxidectin

Faeces voided by 1-year old cattle at 3-70 days after treatment with a pour-on formulation of moxidectin had no detectable effects on development or survival of the common dung beetle Onthophagus taurus. In contrast, faeces voided by cattle treated with a pour-on formulation of eprinomectin were associated with high juvenile mortality during the first 1-2 weeks after treatment. Increased mortality also occurred among newly emerged beetles fed on faeces collected 3 days after eprinomectin treatment and there was evidence of suppressed brood production among those that survived. This effect was still apparent even after insects fed for a further 10 days on the faeces of untreated cattle. A model simulating the effects of drug residues on dung beetle populations suggests that in the absence of immigration a single treatment of eprinomectin is capable of reducing beetle activity in the next generation by 25-35%. Effects are likely to be greatest when treatment coincides with emergence of a new generation of beetles.     

Field efficacy of minidosed pour-on ivermectin and eprinomectin against goat warble fly infestation by Przhevalskiana silenus

The efficacy of minidose of pour-on ivermectin and eprinomectin formulations against first instar larvae of Przhevalskiana silenus was observed in naturally infested goats in the Jammu region, North India. The study was performed in mid August 2011. A total of 280 goats were randomly divided in to 7 groups of 40 each. Goats of the first three groups were treated with pour-on ivermectin at dosage of 2, 5, and 200 μg/kg body weight, respectively, whereas animals of the fourth to sixth groups were treated with pour-on eprinomectin at 25, 50, and 500 μg/kg body weight, respectively. Group VII animals were kept as untreated control. The results indicated that no warbles were recorded between December 2011 and March 2012 on back of animals treated with pour-on preparations of ivermectin at dosage of 5 and 200 μg/kg body weight, respectively, and eprinomectin at dosage of 50 and 500 μg/kg body weight, respectively. Thus, it is concluded that administration of minidose of pour-on ivermectin (5 μg/kg body weight) and eprinomectin (50 μg/kg body weight) is cost effective and so can be used for warble fly control campaign in Jammu region.     

Effect of eprinomectin treatment on milk yield and quality in dairy cows in South Tyrol, Italy

The effect of treatment with eprinomectin on milk yield, milk composition and somatic cell counts (SCCs) was studied in 105 dairy cows located on seven farms in South Tyrol, Italy. On each farm, half of the animals were treated with eprinomectin and the other half were used as an untreated control group. Three test day records per animal were obtained before treatment (days -117, -75 and -33) and another three test day records were obtained after treatment (days 22, 62 and 131). Test day records comprised milk yield, milk composition, SCC and days in milk. On the day of treatment, blood samples and faecal samples were taken for parasitological analysis. Cows with positive faecal egg counts yielded less milk. A significant effect of eprinomectin on milk yield was observed after treatment and was most pronounced on the second and the third test days after treatment (+1.90 kg [P=0.002] and +2.63 kg [P<0.001], respectively). Furthermore, a significant decrease in SCC was observed on the second test day after treatment.     

An evaluation of the quality and physical properties of calf leather following topical application of eprinomectin

The gross and histological appearance of skins obtained from twelve 6–10 month-old Friesian × Hereford calves 14–15 days after they were treated with a topical formulation of 0.5% eprinomectin administered at 1 ml per 10 kg bodyweight was compared to that of skins from twelve untreated controls. No significant differences were observed and there were also no significant differences in the quality and physical properties of leather produced from the skins of treated and untreated groups, indicating that topical eprinomectin has no deleterious effects on the leather quality of calf skins.