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1.
Ivermectin, the antiparasitic drug from the macrocyclic lactones class raises attention due to its high efficiency against nematodes and arthropods and very specific toxic and side effects that it may produce in host. Dominant clinical symptoms of adverse effects and toxicity of ivermectin in animals are tremor, ataxia, CNS depression and coma which often results in mortality. In our study increasing intravenous doses of ivermectin, (6 or more times higher than therapeutic dose: 1.25, 2.5, 3.75, 5.0, 6.25 and 7.5 mg/kg), caused dose-dependent disturbance of motor coordination in treated rats. The median effective dose (ED50) that was able to impair the rota-rod performance in rats treated 3 min before testing was 2.52 mg/kg. This effect weakens over time, while in the rats treated 60 min before the rota-rod test, ED50 of ivermectin was 4.21 mg/kg. Whereas, all tested doses of ivermectin did not cause any other clinical symptoms of toxicity. Ivermectin has no effect on the contractions of isolated diaphragm caused by the EFS, which effectively blocked mecamylamine (100 μM) and pancuronium (1 and 2 μM). Effect on motor coordination is the first detectable clinical symptom of ivermectin toxicity and apparently is a result of its central effects.  相似文献   

2.
Ivermectin is considered a very safe drug; however, there are reports of toxic effects in particularly sensitive populations or due to accidental overdose. The aim of this study was (1) to further characterize the central and peripheral toxic effects of ivermectin in animals and (2) to determine possible therapeutic strategies for use in cases of ivermectin poisoning. We tested the effects of experimental doses of ivermectin previously reported to cause various intensities of CNS depression. However, in our study, ivermectin at 2.5, 5.0 and 7.5 mg/kg i.v. did not produce visible CNS depression in rats and 10 mg/kg resulted in sleepiness and staggering 10 to 40 min after application, while a dose of 15 mg/kg caused CNS depression very similar to general anesthesia. Ivermectin dose-dependently potentiates thiopentone-induced sleeping time in rats. Flumazenil (0.2 mg/kg), the benzodiazepine antagonist, did not affect the action of thiopentone; however, it significantly reduced sleeping time in rats treated with a combination of ivermectin (10 mg/kg) and thiopentone (25 mg/kg; from 189.86 ± 45.28 min to 83.13 ± 32.22 min; mean ± SD). Ivermectin causes an increase in the tonus (EC(50)=50.18 μM) and contraction amplitude (EC(50)=59.32 μM) of isolated guinea pig ileum, very similar to GABA, but without the initial relaxation period. These effects are dose-dependent and sensitive to atropine. Our results confirm the central and peripheral GABAergic properties of ivermectin in mammals and also indicate involvement of the cholinergic system in its toxicity. In addition, the results suggest that flumazenil and atropine have potential clinical roles in the treatment of ivermectin toxicity.  相似文献   

3.
探讨伊维菌素对雄性动物生殖功能的影响,为临床用药安全和动物繁殖提供依据。试验选取成年雄性大白鼠,按照0.17 mg/kg（低剂量组）,3 mg/kg（中剂量组）,5 mg/kg（高剂量组）的剂量分别进行灌胃,对照组以生理盐水代替药物进行灌胃。末次给药后24 h处死大鼠,取睾丸、附睾进行生殖系统毒性检查。试验结果表明：当伊维菌素用药剂量达到3 mg/kg以上就呈现出一定的生殖毒性,睾丸系数、附睾系数下降,精子密度和精子活率下降,但对精子活力并没影响,4个试验组均未显示与剂量的相关性。  相似文献   

4.
Ivermectin is one of the most commonly used drugs in pharmacotherapy of parasitic diseases in domestic and wild animals caused by parasitic nematodes and arthropods. However, ivermectin and other avermectins very often produce side-effects in hosts. The most dominant clinical symptom of ivermectin toxicity in domestic and wild animals is CNS depression. In nematodes, the target site of ivermectin’s action is glutamate-gated chloride-channel receptor and GABA receptor. The depressive effect of ivermectin in mammals might include more than one mechanism; therefore, the anticonvulsive effect of ivermectin against convulsions caused by lidocaine and strychnine was evaluated. Ivermectin antagonized lidocaine- and strychnine-induced convulsions in rats, although these have different mechanisms. In the present study, the anticonvulsive ED50 of ivermectin for lidocaine-induced convulsions was 2.44 mg/kg (95% CL 1.67 to 3.57 mg/kg), whereas for convulsions induced by strychnine it was higher at 4.25 mg/kg (95% CL 2.32 to 3.78 mg/kg). At the same time, both anticonvulsive doses are significantly lower then the observed LD50 of ivermectin (18.20 mg/kg). Furthermore, flumazenil (0.1 and 0.2 mg/kg), an antagonist of benzodiazepine receptors, antagonizes just one part of these anticonvulsive effects of ivermectin. Our results show the significant anticonvulsive properties of ivermectin and support the findings that ivermectin in the CNS of mammals produces multiple inhibitory effects, probably through participation in the function of GABA-sensitive and GABA-insensitive chloride channels.  相似文献   

5.
Ivermectin administered cutaneously at dosages of 2 mg/kg of body weight eliminated nematode infections in leopard frogs. Three clinical trials were conducted. In the first trial, 5 groups of 11 frogs were given ivermectin IM at dosages of 0, 0.2, 0.4, 2, or 20 mg/kg. All frogs given ivermectin IM at dosages of 2.0 mg/kg or greater died. In trial 2, 44 frogs, allotted to 5 groups, were given ivermectin cutaneously at 0, 0.2, 2, or 20 mg/kg. Cutaneously administered ivermectin was not toxic at dosages up to 20 mg/kg. In trial 3, nematode infections were eliminated in all 10 frogs treated cutaneously with ivermectin at 2.0 mg/kg.  相似文献   

6.
伊维菌素脂质体的急性毒性试验   总被引：2，自引：0，他引：2  
为了解伊维菌素脂质体的毒性，将伊维菌素脂质体给试验小鼠按一定浓度一次腹腔注射，连续观察7-14d，用改良寇氏法计算半数致死量（LD50）及95％的可信限，并在同一方法和条件下与伊维菌素注射剂相比较。结果表明，伊维菌素脂质体（脂质体组）的LD50（92．1516mg／kg．BW）显著高于伊维菌素注射剂（原药组）的LD50（24．2493mg／kg．BW），是原药组的3．80倍。证明伊维菌素脂质体的毒性更低，刺激性更小，安全范围更广。  相似文献   

7.
Ivermectin, a mixture of 22,23-dihydroavermectin B1a (80%) and B1b (20%), is produced by Streptomyces avermectilis, an actinomycete. It is a macrocyclic lactone disaccharide, a member of the avermectin family, and is used as an antiparasitic drug. Previous studies performed in our laboratory showed that doramectin, another avermectin drug, interferes with GABAergic-related behaviours, leading to anxiety and seizures. The objective of the present study was to examine the effects of ivermectin (0.5 and 1.0 mg/kg) on the central nervous system of rats, using behavioural models related to GABAergic neurotransmission. A known anxiolytic drug, diazepam, was used as a positive control. Open field and elevated plus-maze behaviours, as well as conflict behaviour to a conditioned response, were assessed. The effects of ivermectin and diazepam in reversing the anxiety induced by picrotoxin was studied. The protective effects of ivermectin on pentylenetetrazole- and picrotoxin-induced seizures were also investigated. In the open field, 1.0 mg/kg ivermectin decreased locomotion frequency at 15 and 60 min of observation, rearing behaviour showed a biphasic effect at 15 and 30 min and duration of immobility was increased in all sessions after 1.0 mg/kg ivermectin. These data suggest anxiolytic or sedative effects. Ivermectin and diazepam both had a tendency to cause an increase both in the number of entries into the open arms and on the time spent in the open arms of an elevated plus-maze. Picrotoxin on its own reduced the number of entries as well as the time spent in the open arms. Both diazepam and ivermectin reversed these effects of picrotoxin. In conflict behaviour analysis, ivermectin and diazepam gave the classic effect of an anxiolytic drug, reversing the conditioned response to shock. Ivermectin protected rats from the convulsant effects of pentylenetetrazole but not from those of picrotoxin. Thus, ivermectin had the pharmacological profile of an anxiolytic drug with GABAergic properties. The lack of effect on seizures induced by picrotoxin suggests that the action of ivermectin is different from that of the benzodiazepine drugs.  相似文献   

8.
Ivermectin (IVM) is an antiparasitic drug, widely used in domestic animals. In mammals, IVM act as a GABA agonist. This neurotransmitter has an important role in the regulation of sexual behavior. Thus, this study sought to investigate the effects of various medically relevant doses IVM on the sexual behavior of male rats. In particular, we also wished to examine if previous sexual experience modulated responses to IVM. In the first experiment, the sexual behavior of inexperienced male rats was analyzed after they received 0.2, 0.6, 1.0 or 2.0 mg/kg IVM, 15 min prior to behavioral testing. In the second experiment, the effects of four previous sexual experiences on IVM treated rats (1.0 or 2.0 mg/kg, 15 min prior to the 5th session) were assessed. The standard therapeutic dose (0.2 mg/kg) did not impair the sexual behavior of inexperienced male rats. At a more concentrated dose (0.6 mg/kg), which is still within the therapeutic range, the appetitive phase of sexual behavior of inexperienced male rats was impaired. Likewise, 1.0 mg/kg impaired the appetitive phase. Previous sexual experience blocked almost entirely this sexual impairment, suggesting that previous sexual experience exerts a positive effect in attenuating the sexual impairment produced by IVM treatment. Therefore, the standard therapeutic dose of IVM can be used without producing side effects on sexual behavior. Use of more concentrated therapeutic doses is not recommended during reproductive periods, unless the animals have had previous sexual experience.  相似文献   

9.
The efficacy of ivermectin against Heligmosomoides polygyrus was investigated in 5 mouse strains (CFLP, NIH, C57Bl10, BALB/c and CBA) using a variety of dose levels, and subcutaneous and oral administration. Heligmosomoides polygyrus were not completely eliminated when 5 mg kg-1 of ivermectin was given 6 days after infection, but 10 mg kg-1 was totally effective. Significant mouse-strain variation in drug efficacy was detected, NIH mice requiring treatment with higher doses than CFLP mice in order to bring about a comparable level of larvicidal activity. Ivermectin was more effective when given subcutaneously than when given orally, regardless of the dose administered or the strain of mouse tested. The anthelmintic effect of the treatment was more persistent in CFLP mice given 20 mg kg-1 subcutaneously than in NIH mice or in mice treated orally, and a 20-day interval between administration and infection was insufficient to prevent inhibition of parasite survival. Ivermectin was shown to be totally effective at 20 mg kg-1 given subcutaneously in killing immune arrested larvae of H. polygyrus.  相似文献   

10.
Ivermectin and piperazine toxicoses in dogs and cats   总被引：1，自引：0，他引：1  
Review of all reports involving anthelmintics in dogs and cats to the IAPIC between January 1, 1986 and August 10, 1988, revealed that ivermectin (extra-label use) and piperazine accounted for over 50% of the calls assessed as toxicoses and suspected toxicoses. Both ivermectin and piperazine are gamma-aminobutyric acid (GABA) agonists and their major effects appear to be on the central nervous system. Ivermectin toxicoses at estimated doses of greater than or equal to 100-less than 500 micrograms/kg were reported more than once only in the collies (n = 25) and Australian shepherds (n = 10); these two breeds accounted for 46% (69 of 150) of the toxicoses and suspected toxicoses calls in dogs. Ataxia, behavioral disturbances, tremors, mydriasis, weakness/recumbency, apparent blindness, hypersalivation/drooling (dogs only), and coma were the most commonly reported clinical signs in dogs and cats with suspected ivermectin toxicoses. Shock, dyspnea, vomiting, and ataxia were the most common clinical signs attributed to the microfilaricidal activity of ivermectin. Piperazine was the anthelmintic with the greatest number of reports of toxicoses and suspected toxicoses in cats. Piperazine neurotoxicity in cats and dogs usually was manifested by muscle tremors, ataxia, and/or behavioral disturbances within 24 hours after estimated daily dose(s) between 20 and 110 mg/kg.  相似文献   

11.
Twenty adult dogs (11 Cocker spaniels and 9 miniature Poodles) with naturally occurring cheyletiellosis were treated twice, at a three-week interval, with subcutaneous injections of ivermectin at the dose rate of 300 μg/kg. Ivermectin proved to be very effective against Cheyletiella yasguri infestation in dogs. All treated animals were completely cured after one or two treatments. No adverse reactions were noted. Ivermectin should be avoided in Collies and Collie crosses.  相似文献   

12.
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.  相似文献   

13.
为观察伊维菌素浇泼剂、注射剂对牦牛皮蝇蛆病的防治示范效果,选择放牧饲养的牦牛,伊维菌素浇泼剂按0.5mg/kg体重剂量沿背中线浇泼给药,伊维菌素注射剂按0.2mg/kg体重剂量颈部皮下注射给药,同时留未防治的对照群,分别在3、5月份采用触摸法抽样进行防治效果检查。结果:伊维菌素浇泼剂防治示范组牦牛2次检查的皮蝇蛆感染率在1.61%~3.23%之间,平均感染率2.42%,查出瘤疱和皮肤虫孔总数7个,平均感染强度1.75个,感染范围0~2个。2次检查未防治的对照组牦牛皮蝇蛆感染率在33.33%~38.89%之间,平均感染率为36.11%,查出瘤疱和皮肤虫孔总数152个,平均感染强度4.22个,感染范围0~14个。结果表明:伊维菌素浇泼剂防治示范组牦牛皮蝇蛆病治愈率为98.39%,驱虫率99.08%~99.54%,平均驱虫率99.31%;伊维菌素注射剂防治示范组牦牛皮蝇蛆病治愈率在98.39%~100.0%之间,平均治愈率为99.20%,驱虫率98.62%~100.0%,平均驱虫率99.31%。2种剂型的推荐剂量均达到了高效安全,可在高寒牧区牦牛皮蝇蛆病防治中推广应用。  相似文献   

14.
The distribution and some pharmacokinetic parameters of ivermectin in pigs   总被引：4，自引：0，他引：4  
Ivermectin was injected subcutaneously into five pigs at the usual dose rate of 300 µg/kg and found to distribute well to all tissues and body fluids which were sampled 24 h post-injection. Ivermectin was detected in the contents and mucus at all levels of the gastrointestinal tract. The drug was excreted in bile, with high concentrations of the drug in the intestines and faeces. High concentrations of ivermectin were measured in skin, ears and ear wax, suggesting that the drug should be effective in the treatment of ectoparasitic infestations, particularly ear mites. The high lipid solubility of the drug may explain the high concentrations found in ear wax and skin. Ivermectin was also detected in the body fluids and tissues of an untreated pig penned with the treated animals. Direct contact appeared to be necessary for transfer of ivermectin from the treated to the untreated pig but coprophagia or urine drinking is a possible explanation.The pharmacokinetics of ivermectin administered subcutaneously at a dose rate of 300 µg/kg to six pigs were studied. There was marked individual variation in the pharmacokinetics of ivermectin. In one pig the area under the plasma concentration-time curve was particularly high. This may reflect individual variation in uptake and excretion of the drug. The mean elimination half-life of the drug was 35.2 h, suggesting that the drug is cleared slowly from pigs with drug detectable in plasma for 6–10 days. This persistence should allow a short period of protection before re-infection with parasites.  相似文献   

15.
The pharmacodynamics of ivermectin in sheep and cattle   总被引：8，自引：0，他引：8  
The concentrations of ivermectin in the gastrointestinal tract of sheep and cattle were determined after subcutaneous administration of ivermectin. Ivermectin was not detected (limit of detection 1 ng/ml) in abomasal and ruminal fluids either after a normal therapeutic dose of 200 micrograms/kg or even at an increased dose of 2000 micrograms/kg. It was also not detected in abomasal and ruminal fluids of a sheep infected with the abomasal parasite Ostertagia circumcincta. However, ivermectin was detectable at similar concentrations in abomasal mucus and in small intestinal mucus. Excretion of ivermectin was high in bile but the concentrations in small intestinal mucus, distal and proximal to the bile duct opening, were similar. It is hypothesized that the low efficacy of ivermectin against small intestinal nematodes compared with abomasal nematodes is not due to differences in ivermectin concentrations in the predilection sites but is probably due to tachyphylaxis in the nematodes allowing the small intestinal nematodes to re-establish before they have left their predilection site. Ivermectin was excreted in the milk of ewes at concentrations similar to those in plasma. Lambs suckling ivermectin-treated ewes received about 4% of a normal therapeutic dose (200 micrograms/kg) via the milk.  相似文献   

16.
The efficacy of ivermectin was evaluated against Melophagus ovinus in Darab ecotype goats of Iran. Twenty-four healthy Iranian crossbreed male goats were randomly divided into three equal groups (n = 8). An experimental infestation was induced in all animals of the three groups with 100 M. ovinus on the body of each animal. Groups 1 and 2 were treated with 1% ivermectin solution at a dosage of 0.5 mg/kg of body weight applied as a pour-on along the dorsal midline and 0.2 mg/kg subcutaneously, respectively; while group 3 was kept as control group. Seven days after infestation ivermectin was administered then the goats were observed for a period of 7 days. Body surface of each goat of three groups was inspected daily and decreases in M. ovinus were recorded. The rate of elimination in keds was assessed on the basis of decrease in keds count on the skin and hairs. The results revealed that complete absence of keds were observed in 6 and 7 days post-treatment with injection and pour-on routes, respectively. The results of present study showed that subcutaneous injection of ivermectin more rapidly eliminated M. ovinus than pour-on route. Both routes were 100% effective against this parasite in the goats. Ivermectin can be a drug of choice against M. ovinus in long-hair Iranian goats due to its high efficacy, easy applicability and wide safety margin.  相似文献   

17.
为了探讨复方伊维菌素乳液在动物体内的药物代谢,为兽医临床提供用药参考。试验选取7只山羊,每只山羊按0.1 mL/kg (伊维菌素0.2 mg/kg, 阿苯达唑10 mg/kg)剂量口服,给药后0.5、1、2、3、4、6、8、12、16、24、36、48、60 h颈静脉采血5 mL,分离血清,-20 ℃保存,用高效液相色谱仪检测样品血药浓度。试验结果表明,①伊维菌素在山羊体内的代谢情况为：0.5 h,0.112151 μg/mL; 第1次达峰时间为4 h, 0.302702 μg/mL;第2次达峰时间为16 h,0.258284 μg/mL;60 h,0.011118 μg/mL。②阿苯达唑在山羊体内的代谢情况为：0.5 h, 0.049285 μg/mL;第1次达峰时间为8 h,4.95283 μg/mL ;第2次达峰时间为16 h,5.694551 μg/mL;60 h,0.06434 μg/mL。复方伊维菌素中的伊维菌素和阿苯达唑在山羊体内代谢时间短,第60小时已达到很低的血药浓度。  相似文献   

18.
The tissue concentration and efficacy of ivermectin after per os and subcutaneous administration were compared in goats experimentally infected with Trichostrongylus colubriformis (ivermectin-susceptible strain, INRA). Infected goats (n = 24) were treated per os (n = 9) or subcutaneously (n = 9) with ivermectin, 0.2 mg/kg, or kept as not treated controls. The faecal egg counts and small intestine worm counts were determined. Ivermectin concentration was measured in the plasma, gastrointestinal tract, lung, skin or hair, liver and adipose tissues at 0, 2, 7 and 17 days post-treatment. The efficacy of ivermectin against T. colubriformis infection in goat was 98.7 and 99.9% for subcutaneous and oral administration, respectively. Ivermectin concentration declined with time and only residual concentration was measured at 17 days post-treatment in plasma and gastrointestinal tract. Ivermectin concentration was higher after subcutaneous compared to per os injection in most of the tissue examined. In skin, hair and subcutaneous adipose tissue ivermectin persisted at significant concentrations 17 days post-treatment for both routes of administration. In our experimental conditions, ivermectin provides similar efficacy against T. colubriformis after subcutaneous or per os administration in goat. However, the lower ivermectin levels in tissues after per os administration suggest that the lasting of efficacy may be shortened after per os compared to subcutaneous administration especially in animals with poor body condition in pasture where re-infection occurs quickly after anthelmintic treatment.  相似文献   

19.
Ivermectin resistance in the nematode Haemonchus contortus has been reported in many parts of the world and many ivermectin resistant isolates have been found to have reduced sensitivity to moxidectin. However, it is unclear whether parasites that are selected with moxidectin would demonstrate reduced sensitivity to ivermectin. In this study, the effects of moxidectin and ivermectin on an unselected strain and a strain of H. contortus derived from the unselected strain but selected over 14 generations with moxidectin, were compared in jirds. The recovery of adult worms and fourth stage (L4) larvae following treatment were compared between strains and anthelmintics. Moxidectin-selected H. contortus showed reduced sensitivity to ivermectin as well as to moxidectin. Doses of 0.1 mg/kg of moxidectin and 0.4 mg/kg of ivermectin were necessary to obtain an efficacy of 95% or above against the moxidectin-selected strain of H. contortus compared with 0.025 mg/kg for moxidectin and 0.1 mg/kg for ivermectin required for a similar efficacy in the unselected strain.  相似文献   

20.
Treatment protocols for demodicosis: an evidence-based review   总被引：4，自引：3，他引：1  
Publications discussing the treatment of demodicosis in the dog and cat are reviewed. Based on the evidence in the literature, amitraz rinses at 0.025-0.06% every 7-14 days, and oral daily ivermectin at 300 micro g kg(-1), milbemycin at 2 mg kg(-1) and moxidectin at 400 micro g kg(-1), respectively, can all be recommended for the treatment of generalized canine demodicosis. Ivermectin and moxidectin should be initiated at lower doses and patients monitored for possible adverse effects during therapy. In cats, 2% lime sulfur dips and amitraz rinses at 0.0125-0.025% have been used successfully.  相似文献   

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