Letteratura scientifica selezionata sul tema "Eprinomectine"

Abstract Eprinomectin, moxidectin, abamectin, doramectin, and ivermectin are drugs used to control parasitic infections in both meat-producing and nonmeat-producing animals. A number of analytical methods are available to analyze these anthelmintic drugs individually. A multiresidue screening method was developed for these drugs; however, the initial attempt to derivatize eprinomectin following the method published by Merck scientists was unsuccessful because the eprinomectin derivatization reaction was temperature- and time-dependent. The optimum time and temperature for the completion of eprinomectin derivatization were 90 min and 65°C, respectively, without appreciable effect on the remaining 4 drugs. Beef liver samples were fortified with 0, 25, 50, and 100 ppb mixed standards of eprinomectin, moxidectin, abamectin, doramectin, and ivermectin. Each set of 4 levels of recoveries was repeated 10 times with all 5 compounds. The average of 10 recoveries of 5 compounds at all 4 levels of fortification was > 70%; the coefficient of variation was < 20%.

The distribution of eprinomectin in goat milk and cheeses (cacioricotta, caciotta, caprilisco) with different ripening times following a pour-on administration at a single dose rate (500 μg/kg of body weight) and a double dose rate (1,000 μg/kg of body weight) to goats with naturally occurring infections of gastrointestinal nematodes was studied. Milk residues of eprinomectin reached a maximum of 0.55 ± 0.18 μg/kg and 1.70 ± 0.31 μg/kg at the single and double doses, respectively. The drug concentrations decreased progressively until the fifth day after treatment, when they were less than the detection limit at both dose rates. The eprinomectin levels measured in all cheese types (both treatments) were higher than those recovered in milk at all the sampling times. In caciotta cheeses, the eprinomectin residues levels were constantly higher than other cheeses. With the exception of cheeses made with milk the first day after treatment, eprinomectin concentrations were nearly constant up to the fourth day then decreased by the fifth and sixth days after treatment. In all cases, at both the single and double dosages, the maximum level of eprinomectin residues in goat milk and cheeses remained below the maximum residual level of 20 μg/liter permitted for lactating cattle.

Abstract Objective To assess the nematocidal efficacy of eprinomectin in naturally infected cattle. Animals 62 (31 eprinomectin-treated and 31 control) beef mixed-breed or Holstein cattle, either 6 to 11 or 48 to 96 months old. Procedure Cattle were housed 21 to 27 days before treatment to allow parasites to reach maturity. Animals were grouped by sex, ranked by weight, and randomly assigned to treatment group. Fecal flotation was done to identify cattle with intestinal nematode infections. Treatment groups were: 1—eprinomectin topical vehicle (1 ml/10 kg) and 2—eprinomectin topical solution (1 ml/10 kg). Cattle were euthanatized by replicate on day 14 or 15, and standard procedures were used to recover of pulmonary, abomasal, small intestinal, and large intestinal nematodes. Results Eprinomectin efficacy across all trials was 100% against adult Trichostrongylus axei, Haemonchus placei, Oesophagostomum radiatum, and Dictyocaulus viviparus, as well as fourth-stage larval Oes radiatum, Ostertagia ostertagi, Nematodirus helvetianus, and Cooperia spp. Efficacy against adult O ostertagi, Cooperia oncophora, C punctata, C surnabada, C spatulata, N helvetianus, Trichuris sp, and Trichuris fourth-stage larvae was 99.9, 99.8, 99.6, 98.9, 98.3, 99.7, 97.8, and 84.3%, respectively. All results were significant (P < 0.01) except those for C spatulata. Adverse reactions were not observed. Conclusion and Clinical Relevance Eprinomectin is a safe and effective nematocide against naturally acquired nematode infections in cattle when administered at a dosage of 500 μg/kg. Milk and meat withholding is not necessary when using this product. (Am J Vet Res 1997;58:612–614)

Abstract Macrolide endectocides (abamectin, doramectin, emamectin, eprinomectin, ivermectin, and moxidectin) are used to treat animals against a variety of parasites. They are approved for use with food animals, but require long withdrawal times. Two compounds, eprinomectin and moxidectin, are approved for use with lactating cattle and have established maximum residue limit values of 20 and 40 g/kg, respectively. The remaining compounds may appear in milk if there is off-label or accidental use. This method is capable of quantitating and confirming the presence of six of the macrolide endectocides over the concentration range 160 g/kg (parts per billion). Selamectin is used as the internal standard. The compounds are extracted with C18 solid-phase extraction under basic conditions and quantitated by negative ion LC-MS/MS using one selected reaction monitoring transition, with a second transition used for verification. The limits of detection were determined from between-day experiments as 0.14, 0.14, 0.18, 0.24, 0.25, and 0.25 g/kg for abamectin, doramectin, emamectin, eprinomectin, ivermectin, and moxidectin, respectively. The detection capability CC for eprinomectin was measured as 28.5 g/kg, and 50.0 g/kg for moxidectin using five milk matrices.

SUMMARY Objective To determine the efficacy of a topical formulation of eprinomectin against natural infestations of first (L1)-stage, and second and third (L2/L3)-stage larvae of Hypoderma spp. Animals 140 approximately 6- to 18-month-old cattle of various breeds. Procedure Cattle, selected from herds with high prevalence of Hypoderma infestation, were treated in 4 experiments: within each replicate, 1 animal received eprinomectin at a dosage of 500 μg/kg of body weight against first-stage larvae (L1). The second animal received the same treatment against second or third-stage larvae (L2/L3). The third animal served as an untreated control. In a fifth experiment, visible warbles were treated on half of the cattle. Remaining cattle served as vehicle-treated controls. In 1 experiment, warbles were examined from time of treatment until all lesions were resolved. In 4 experiments, emerging Hypoderma larvae were recovered, speciated, and enumerated, and viability was determined. Results Eprinomectin (500 μg/kg) efficacy was complete against L1. Hypoderma L2/L3 eradication approached 100% efficacy (1 live larva was recorded). Warbles in treated cattle resolved in a significantly shorter time than did those in controls. Adverse reactions related to treatment were not observed in any of the trials. Conclusions Eprinomectin (500 μg/kg) applied topically was safe and highly efficacious for treatment of all larval stages of Hypoderma spp in these trials. Clinical Relevance Attributes of eprinomectin besides antiparasite efficacy allow treatment of all classes of cattle with no need for meat or milk withdrawal. (Am J Vet Res 1998;59:56–58)

AbstractThe efficacy of eprinomectin on Dictyocaulus filaria and Cystocaulus ocreatus in naturally infected sheep was evaluated in the present study. In total, 30 infected sheep were randomly divided into two groups: treated (n = 15) and untreated (n = 15). A single pour-on dose of eprinomectin (0.5 mg/kg) was administered to the treated group. No medication was used in the untreated group. Faecal larval counts were performed on pre-treatment (day 0) and post-treatment (days 7, 14, 21 and 42) days. Eprinomectin was found to be 100% effective against D. filaria on day 7 post-treatment when compared with the untreated group and it maintained this effect on days 14, 21 and 42. However, the decrease in faecal larval count of C. ocreatus was found to be 86, 86 and 91%, on days 14, 21 and 42, respectively.

Esafoxolaner, a purified enantiomer of afoxolaner with insecticidal and acaricidal properties, is combined with eprinomectin and praziquantel in NexGard®Combo, a novel topical endectoparasiticide formulation for cats. The parasiticide potencies of topical esafoxolaner, eprinomectin and praziquantel, are based on transcutaneous absorption, systemic distribution, and exposure of respective target parasites. For each compound, the pharmacokinetic profile, non-interference, dose linearity/proportionality after one administration, and the accumulation and time to reach a steady state after repeated monthly administrations of the novel formulation, were investigated. After one topical application of NexGard®Combo at the minimum recommended dose, the mean plasma concentration of esafoxolaner immediately reached (and remained at) a level supporting rapid onset and sustained efficacy against ectoparasites for at least 1 month. The meanCmax,Tmax,T1/2, and the topical bioavailability of esafoxolaner were 130 ng/mL, 7.1 days, 21.7 days and 47.2%, respectively, and the plasma profiles of eprinomectin and praziquantel supported their known endoparasiticide properties. No relevant interference between the three compounds was observed. Dose proportionality was demonstrated for the three compounds over a range of 0.5× to 2× the minimum recommended dose. Steady state after repeated monthly administrations was reached by the second dose for praziquantel and by the fifth dose for esafoxolaner and eprinomectin. Accumulation was limited and drug plasma concentrations were maintained within a safe level.

Abstract A simple multiresidue analysis method was developed for the confirmation and quantification of eprinomectin, abamectin, doramectin, and ivermectin in cattle liver. The target analytes were extracted with acetonitrile and cleaned up with C18 and C8 solid-phase extraction cartridges before analysis by liquid chromatography combined with positive ion electrospray tandem mass spectrometry. The residue mean recoveries of the 4 drugs were 64.1699.53%. The limit of detection was 2.5 ng/g for eprinomectin, abamectin, doramectin, and ivermectin.

AbstractPour-on formulations of four endectocide products were compared to assess the effect of faecal residues on insects developing in naturally-colonized dung of treated cattle. In each of three independent experiments, suppression of insects was associated with application of doramectin, eprinomectin and ivermectin, but no effect was observed for moxidectin. When data were combined across experiments to increase sample sizes, suppression of insects was observed for each compound, with the least effect being observed for moxidectin. Based on the number of species affected and duration of suppression, doramectin > ivermectin > eprinomectin ≫ moxidectin were ranked in descending order of adverse effect. A second set of three independent experiments was performed to assess the effect of endectocide treatment on dung degradation. Delayed degradation was observed for dung of cattle treated with doramectin, eprinomectin and moxidectin in the first experiment. No effect of treatment was detected in the second experiment. An effect of moxidectin was detected in the third experiment, but differences could not be detected with subsequent post-hoc tests. When data were combined across experiments to increase sample sizes, delayed degradation was detected only for eprinomectin. The apparent discrepancy between the low effect of moxidectin on insects versus its effect of dung degradation suggests the confounding action of other unidentified factors. Results of the current study indicate that use of moxidectin is least likely to affect the natural assemblage of insects associated with cattle dung.

Abstract The avermectin and milbemycin families of compounds are derived from naturally occurring yeasts. They have proven to be potent preventatives against a variety of pests such as insects and parasites. Only eprinomectin and moxidectin are currently approved for use on lactating cattle with tolerances in milk of 12 μg/kg for eprinomectin and 40 μg/kg for moxidectin. Detection of misuse or inadvertent contamination in milk requires a sensitive and definitive analytical method. A method has been developed for the determination of 5 avermectins and 1 milbemycin in milk using a simple liquidliquid extraction and liquid chromatography/tandem mass spectrometry (LC/MS/MS) analysis. Ivermectin (IVR), doramectin (DOR), abamectin (ABA), eprinomectin (EPR), emamectin (EMA), and moxidectin (MOX) were extracted from whole milk by partitioning into acetonitrile with a subsequent solvent exchange into methanolwater. Simultaneous confirmation and quantification were achieved with LC separation, positive electrospray ionization (ESI+), and MS/MS. The limits of detection ranged from 16 pg/g (ppt) for EMA to 1.7 μg/g (ppb) for MOX.

Au pâturage, les ovins sont inévitablement exposés aux strongles gastro-intestinaux (SGI). L’infection par ces parasites peut fortement impacter leur santé et leur bien-être, et peut donc générer des pertes de productions importantes. Au cours des 60 dernières années, ces impacts ont été limités par l’utilisation de molécules anthelminthiques (AH). Le développement au niveau mondial de résistances des principaux SGI pathogènes envers toutes les familles d’AH remet en question la durabilité d’une gestion reposant uniquement sur ces molécules. Ce questionnement est particulièrement important en brebis laitière : la lactation dure entre 6 et 8 mois, et la pharmacocinétique de certaines molécules empêche leur utilisation pendant cette phase, ou impose un temps d’attente couteux pour l’éleveur. Jusque 2014, les benzimidazoles étaient largement utilisés pendant la lactation. Cependant, les résistances croissantes à cette famille et un changement de temps d’attente de 0 jour à minimum 4 a suscité un report massif sur l’éprinomectine (EPN). Cette lactone macrocyclique a initialement été développée pour les bovins laitiers, puis pour les ovins et caprins en 2016 et 2020 en France, pour les formes pour-on et injectables respectivement. Les premières suspicions de perte d’efficacité de l’EPN dans les élevages ovins laitiers en France a motivé des Tests de Réduction de l’Excrétion Fécale (TREF ou FECRT), complétés d’un dosage de la concentration sérique de la molécule pour confirmer la présence de résistance et exclure une éventuelle sous-exposition, ce qui constitue la première partie de ce travail. Le nombre croissant de suspicions de perte d’efficacité, provenant toutes initialement du département des Pyrénées Atlantiques, a motivé une étude sur les facteurs de risque d’apparition de la résistance, et constitue le deuxième volet de cette thèse. Nous avons démontré l’importance de la transhumance dans la diffusion de la résistance aux AH, en soulevant de plus la question de la compatibilité croissante d’Haemonchus contortus aux conditions environnementales en estive à l’aune du réchauffement climatique. Les nombreuses recherches sur les stratégies favorisant les refuges pour limiter l’apparition de résistances lors de traitement AH n’ont pas toujours été traduites en protocoles applicables sur le terrain. Nous avons évalué une stratégie de Traitement Ciblé Sélectif (TCS) sur 5 exploitations dans les 2 principaux bassins de production de brebis laitière français. En traitant les brebis en première lactation et les brebis multipares qu’ils estimaient en mauvais état corporel, les éleveurs ont pu diminuer significativement la charge parasitaire dans leur cheptel tout en maintenant de 13 à 80% des brebis en refuge. Dans 4 des 5 élevages, la principale espèce infectant les brebis était Haemonchus contortus, mais dans les 2 zones les intensités d’excrétion fécales d’œufs étaient différentes. Le traitement sélectif des brebis n’a pas eu d’impact sur la fertilité dans les élevages des Pyrénées Atlantiques. Les brebis non traitées produisaient en moyenne 8 (PA) à 9% (RR) de lait en moins que les brebis traitées. Cette perte de production est à mettre en regard du coût de la résistance, incluant la perte de production pouvant subvenir lorsque le traitement utilisé n’est pas efficace, et en regard des bénéfices d’une d’impact environnementale du traitement. L’efficacité de l’EPN a été maintenue sur la durée de l’étude, quand elle était initialement bonne. L’utilisation d’un AH en TCS doit faire partie d’une gestion intégrée du parasitisme ayant pour objectif un élevage plus résilient, en prenant en l’importance de l’alimentation, de l’immunité de l’hôte et de la gestion du pâturage dans son ensemble
Grazing sheep are inevitably exposed to gastro-intestinal nematodes (GIN). Infection by these parasites can seriously impact their health and well-being, and therefore can also have repercussions upon the production for which they are raised. For the last 60 years, these impacts have mainly been limited using anthelmintic (AH) drugs. However, the increasing worldwide development of resistance of the major pathogenic GIN species to all AH classes brings into question the sustainability of relying solely on chemical solutions. This question is particularly important in dairy sheep: lactations lasts 6 to 8 months, and milk distribution of some drugs makes them banned, or usable only with a withdrawal period that comes at a cost for the producer. Until 2014, benzimidazoles were widely used during the lactation period. The increasing prevalence of resistance to this AH class and an increase of the withdrawal period from 0 to a minimum of 4 days led to a massive report towards eprinomectin (EPN). This macrocyclic lactone was initially developed and marketed for dairy cattle, then for sheep and goats in 2016 and 2020 in France, for the topical and pour-on formulas respectively. The first suspicions of loss of efficacy of EPN in dairy sheep in France motivated Fecal Egg Count Reduction Tests (FECRT) completed with dosage of serum drug concentration to confirm resistance and dismiss under-exposition, and is described in the first part of this work. The increasing number of suspicions of lack of efficacy, all emanating at first from the Pyrénées Atlantiques (PA) département, led to the study in the second part of this work. We highlighted the importance of transhumance in the spread of AH resistance, and we bring into question to which extent changing environmental conditions at high altitudes allow for the increasing importance of Haemonchus contortus in summer grazing pastures. The important focus on research in refugia-based strategies to delay the appearance of resistance has not always been translated into pratical field guides. Working on 5 farms of the 2 main dairy sheep production areas in France, 3 in the Roquefort Region (RR) and 2 in the PA, we evaluated a targeted selective treatment (TST) protocol. By treating the first lactating ewes and the ones they estimated were in bad body condition, farmers significantly reduced the overall parasite load in their flock while leaving 13 to 80% of ewes as refugia. 4 out of the 5 farms were mainly infected with Haemonchus contortus, yet in both areas farms were not facing the same intensity in GIN infection. Selective treatment of ewes didn’t impact their fertility in the PA. Ewes left untreated in both areas produced 8 (PA) to 9% (RR) less milk than their treated counterparts. This production loss should be balanced with the cost of resistance, i.e. the production loss when treating using an inefficient AH, and with the benefits of reducing the environmental impact of the treatment. EPN efficacy was maintained over the duration of the study when initial efficacy was high. Use of AH in a TST should be part of an integrated management plan to make GIN control more resilient, taking into account feed, immunity development, and pasture management

Um total de 168 machos Bos indicus foram abatidos depois de 8, 15, 35, 49, 63, 91, 120 e 154 dias após a aplicação de eprinomectina e ivermectina (convencional e longa ação), e 18 diferentes tecidos comestíveis foram avaliados quanto à concentração de resíduos dessas moléculas para verificar se o período de carência estabelecido garante o esgotamento em todos eles, em níveis abaixo dos limites máximos estabelecidos por agências reguladoras internacionais, com o objetivo de abordar questões relacionadas à barreiras técnico-comerciais entre países. Além disso, visou analisar se a concentração desses resíduos é afetada pelo processamento térmico, para avaliar a coerência de se considerar para produtos enlatados, os mesmos limites determinados para produtos crus. As análises de concentração de resíduos foram feitas por HPLC (sistema LC-MS/MS). Os dados foram transformados para escala \"logaritmo natural\" e foi realizada análise de variância, teste de comparação múltipla, análises de regressão e de correlação. Os resultados demonstraram que os níveis de eprinomectina encontrados foram abaixo de todos os limites máximos de resíduos (LMR), ao longo de todos os períodos e tecidos avaliados. Com relação à ivermectina, padrões diferenciados de distribuição foram observados, porém ao final do período de carência, dos 18 tecidos avaliados, 17 apresentaram concentrações dentro dos LMR, com exceção do sítio de aplicação, em que se observou alto nível de dispersão e valores acima de alguns LMR, mesmo após cumprido o período de carência indicado na bula. Foram observadas correlações significativas (P<0,01) entre concentrações residuais em fígado e em tecidos musculares, sendo que as equações obtidas podem ser úteis em programas de vigilância. O processamento térmico afetou os resultados de concentração de resíduos de ivermectina em alguns músculos testados, que apresentaram concentração significativamente mais elevada (P<0,05) após a esterilização. Conclui-se que a eprinomectina é mais recomendada que a ivermectina, no que tange ao propósito de se evitar violações de LMR; que foram distintos os padrões de distribuição de resíduos em cada tecido avaliado, mas que se respeitado o período de carência, praticamente todos os tecidos estarão abaixo dos LMR estabelecidos internacionalmente, exceto pelo sítio de aplicação; portanto, que o tempo de depleção de resíduos do sítio de aplicação (até abaixo dos LMR) deveria ser considerado para a determinação do período de carência dos medicamentos; e que é fundamental haver uma harmonização dos LMR em esfera global. Além disso, observou-se que o processamento térmico a que os enlatados são submetidos provoca níveis discrepantes (mais elevados) de resíduos em relação aos produtos crus e isso deve ser levado em consideração nas análises de vigilância, pois pode gerar incertezas quanto à possibilidade de violação em mercados importadores.
A total of 168 Bos indicus males were slaughtered after 8, 15, 35, 49, 63, 91, 120 and 154 days post-application of eprinomectin and ivermectin (conventional and long-acting), and 18 different edible tissues were evaluated for the residue concentration of these molecules to verify if the established withdrawal period guarantees depletion in all of them, at levels below the maximum limits established by regulatory agencies around the world, in order to address issues related to technical trade barriers between countries. In addition, it aimed to analyze if the concentration of these residues is affected by thermal processing, to evaluate the consistency of considering for canned goods, the same limits determined for raw products. Residue concentration analyzes were performed using HPLC (LC-MS / MS system). Data were converted into \"natural logarithm\" scale and analysis of variance, multiple comparison test, regression and correlation analysis were performed. Results showed that eprinomectin levels were found to be below all maximum residue limits (MRL) throughout all periods and tissues evaluated. Regarding ivermectin, differentiated distribution patterns were observed, but at the end of the withdraw period, 17 of the 18 tissues evaluated had concentrations within the MRLs, except for the injection site, where a high level of dispersion was observed and values above some of MRLs recommended by the main international regulations, even after having been completed the withdraw period indicated in the instructions. Significant correlations (P <0.01) were observed between residual concentrations in liver and muscle tissues, and the equations obtained may be useful in surveillance programs. The thermal processing affected ivermectin concentration results in some tested muscle types, which had a significantly higher residue concentration (P <0.05) after sterilization. It was concluded that eprinomectin is more recommended than ivermectin for the purpose of avoiding MRL violations; that the residue distribution patterns in each tissue were different, but if the withdrawal period is met, almost all tissues will be below internationally established MRLs except for the application site; therefore, that the depletion time of injection site residues (to below the MRL) should be considered for the determination of the drug withdrawal period; and that harmonization of MRLs is essential in the global sphere. In addition, it has been observed that the thermal processing to which the canned products are subjected causes discrepant (higher) levels of residues in relation to the raw products and this must be taken into account in surveillance analyzes, since it may generate uncertainties as to the possibility of violation in importers markets.

Orientação: Manuel Pequito
A Naturasin® é uma empresa que comercializa cosméticos provenientes de leite de burra. O seu efectivo é constituído pela Raça Asinina de Miranda, em que o seu efectivo é reduzido em Portugal. Considerando o maneio que esta empresa efectua no seu efectivo, estudou-se qual a eficácia dos desparasitantes doramectina em regime extensivo e eprinomectina em regime semi-intensivo em parasitas gastrointestinais. Durante 5 meses efectuaram-se recolhas de fezes para estudos parasitológicos com a aplicação das técnicas de McMaster modificada, Willis, sedimentação e coprocultura. O efectivo estudado era composto por 18 burras das quais 11 estavam em regime extensivo e desparasitadas com doramectina, grupo D1 e 8 em regime semi-intensivo e desparasitadas com eprinomectina, grupo D2. O estudo observou uma diminuição de 66 vezes o OPG no grupo das burras D1, sendo comprovada a eficácia da doramectina neste grupo em regime extensivo. No grupo das burras aleitantes D2, a diminuição do OPG após aplicação da eprinomectina foi de apenas 1,2 vezes, comprovando a não eficácia deste desparasitante neste grupo. Foi observada uma prevalência de 100% de Cyathostomum nas coproculturas. Conclui-se a elevada prevalência de Cyathostomum em asininos associados a estes desparasitantes com os respectivos regimes. Recomenda-se mais estudos nesta área.
Naturasin® is a company that sells cosmetics derived from donkey's milk. Its cash is made up of the Race Assina de Miranda, in which its cash is reduced in Portugal. Considering the management that this company does in its herd, we studied the efficacy of desparasitizer, doramectin in an extensive regimen and eprinomectin in a semiintensive regimen in grastaintestins parasites. In 5 months, stool samples were collected for parasitological studies with the application of the modified McMaster, Willis test, sedimentation and coproculture techniques. The studied population consisted in 18 donkeys, of which 11 were in extensive regimen and dewormed with doramectin, group D1 and 8 in semi-intensive regime and dewormed with eprinomectin, group D2. The study observed a 66-fold decrease in OPG in the D1 donkey group, and the efficacy of doramectin in this extensive group was demonstrated. In the group of D2 motile dams, the decrease in OPG after application of eprinomectin was only 1,2 fold, demonstrating the non-efficacy of this deparasite in this semi-intensive group. A prevalence of 100% of Cyathostomum in coprocultures was observed. The high prevalence of Cyathostomum in asinines associated with these dewormer with the respective regimens is connived. Further studies in this area are recommended.

The term “macrocyclic lactones” refers to a group of drugs typified by the avermectins and milbemycins. The former group includes abamectin, ivermectin, eprinomectin, doramectin, selamectin and emamectin benzoate, while the latter group comprises moxidectin and milbemycin oxime. They are widely used as antiparasitic agents in veterinary medicine, but ivermectin has been widely used in humans for the prophylaxis and treatment of filariasis, onchocerciasis and loiasis, in addition to other parasitic conditions; while more recently, moxidectin has been authorized for the treatment of onchocerciasis. These drugs have excellent safety profiles in routine toxicity tests at low-to-moderate dosages, but at high doses, neurotoxicity, typified by mydriasis, tremors, convulsions, ataxia and locomotor abnormalities and neurodegeneration, occurs. A specific strain of mouse, the CF-1 mouse, is more susceptible to the toxic effects of macrocyclic lactones than other strains. The CF-1 mouse is deficient in P-glycoprotein in the intestinal epithelium and brain endothelium when compared to non-sensitive animals, permitting greater intestinal absorption of these drugs and higher brain exposure. P-glycoprotein is an efflux pump encoded by the ABCB1 gene. Deficiency or disruption of this gene leads to higher toxicity of the macrocyclic lactones and other drugs in this mouse strain. Some dogs, notably but not exclusively the collie, have defective ABCB1 genes, leading to a greater susceptibility to the neurotoxic effects of some macrocyclic lactones. There is no evidence to suggest that these drugs may pose undue risks to humans when used at the recommended therapeutic doses.