The antiparasitic activity of ivermectin in horses

Parenteral administration of ivermectin (22,23-dihydroavermectin B₁) significantly reduced the numbers of adult large and small strongyles, the immature stages of small strongyles, pinworm and ascarid, the microfilariae of Onchocerca cervicalis and gastrophilid bots from naturally infected horses. Strongylus vulgaris, S. edentatus and S. equinus were effectively removed by 0.02 mg/kg. Adult small strongyles, Cyathostomum pateratum, C. catinatum, Cylicocyclus nassatus, C. leptostomus, Cyliostephanus minutus, C. longibursatus and C. goldi, were effectively removed by 0.1 mg/kg. Fourth stage small strongyles (cyathostomes), 4th stage Oxyuris equi, 5th stage Parascaris equorum and the microfilarie of Onchocerca cervicalis were significantly reduced by 0.1 mg/kg also. The stomach bots, Gastrophilus intestinalis and G. nasalis, were effectively removed by 0.02 mg of ivermectin/kg. Analysis of the dose response curves obtained for the nematode and larval dipteran parasites found in these naturally infected horses suggests that a parenteral dose of 0.2 mg/kg ivermectin would produce 95% or more removal of these parasites. The antiparasitic efficacies observed for ivermectin in this controlled trial were equivalent to the efficacies found in an abbreviated critical trial contained within the controlled trial. However, it was calculated that the man—day effort required for data collection from one critical trial horse was the same as for 6 controlled-trial horses.     

The pharmacokinetics of a slow-release theophylline preparation in horses after intravenous and oral administration

The pharmacokinetics of a slow-release theophylline formulation was investigated following intravenous and oral administration at 10 mg/kg in horses. A tricompartmental model was selected to describe the intravenous plasma profile. The elimination half-life (t1/2) was 16.91 ± 0.93 h, the apparent volume of distribution (V _d) was 1.35 ± 0.18 L/kg and the body clearance (Cl_B) was 0.061 ± 0.009 L kg^–1 h. After oral administration the half-life of absorption was 1.24 ± 0.30 h, and the calculated bioavailability was above 100%. Thet1/2 after oral administration was 18.51 ± 1.75 h, only a little longer than that after intravenous administration. The slow release formulation did not exhibit any advantage in prolonging thet1/2 of theophylline in the horse.     

Pharmacokinetics of potassium bromide in adult horses

OBJECTIVE: To determine the pharmacokinetics of potassium bromide (KBr) in horses after a single and multiple oral doses. ANIMALS: Twelve adult Standardbred and Thoroughbred mares. PROCEDURE: Horses were randomly assigned into two treatment groups. In Part 1 of the study, horses were given a single oral dose of 120 mg/kg KBr. Part 2 of the study evaluated a loading dose of 120 mg/kg KBr daily by stomach tube for 5 days, followed by 40 mg/kg daily in feed for 7 days. Serum concentrations of bromide were determined by colorimetric spectrophotometry following drug administration to permit determination of concentration versus time curves from which pharmacokinetic parameters could be calculated. Treated horses were monitored twice daily by clinical examination. Serum concentrations of sodium, potassium and chloride ions and partial pressures of venous blood gases were determined. RESULTS: Maximum mean serum bromide concentration following a single dose of KBr (120 mg/kg) was 284 +/- 15 microg/mL and the mean elimination half-life was 75 +/- 14 h. Repeated administration of a loading dose of KBr (120 mg/kg once daily for 5 days) gave a maximum serum bromide concentration of 1098 +/- 105 microg/mL. The administration of lower, maintenance doses of KBr (40 mg/kg once daily) was associated with decreased serum bromide concentrations, which plateaued at approximately 700 microg/mL. Administration of KBr was associated with significant but transient changes in serum potassium and sodium concentrations, and possible changes in base excess and plasma bicarbonate concentrations. High serum concentrations of bromide were associated with an apparent increase in serum chloride concentrations, when measured on an ion specific electrode. CONCLUSIONS AND CLINICAL RELEVANCE: A loading dose of 120 mg/kg daily over 5 days and maintenance doses of approximately 90-100 mg/kg of KBr administered once daily are predicted to result in serum bromide concentrations consistent with therapeutic efficacy for the management of seizures in other species. The clinical efficacy of this agent as an anticonvulsant medication and/or calmative in horses warrants further investigation.     

Alternative antiparasitic treatment of horses with pyrantel pamoate suspension and ivermectin oral solution compared with horses treated only with ivermectin

A practical parasite control program was evaluated in a 2-year clinical trial using pyrantel pamoate suspension (PYR) and ivermectin oral solution (IVM) in a seasonal rotation program, in comparison with continued use of IVM given at 2-month intervals. At least 15 horses in each of 2 treatment groups were distributed over 8 locations. In the alternation program, IVM was given twice (October, December) during the botfly (Gasterophilus spp.) season and again in April to treat against the lighter botfly season and to kill existing Onchocerca microfilariae prior to heavy Culicoides swarming. Pyrantel was given in February, June and August to continue suppression of strongyle infections and to treat against potentially developing Anoplocephala infections. In the program of IVM continuous use, the drug was given on the same schedule as either treatment on the alternation program.The course of strongyle infections was monitored by fecal sample analyses (EPG) at semimonthly intervals and by larval cultures of treatment pairs prepared at each treatment interval (alternation program) or at 4-month intervals (continuous IVM program). The strongyle egg count numbers were reduced to zero by the first IVM treatment, increased only slightly by the next treatment at 2 months, and repeated the reduced pattern with each treatment for 2 years. The alternation program in the first year had typical responses to each drug: IVM reducing strongyle EPG counts to zero which increased slightly at 2 months, followed by the PYR treatment, which reduced the strongyle egg counts for 4 weeks with rebound at 6 and 8 weeks. At the end of the first year and into the second, the IVM treatments of October and December established a zero or low strongyle EPG pattern which continued through the spring with PYR and IVM treatments. The second summer PYR treatments then maintained far better cyathostome control than had been reported for this drug. There may be a complementary or enhancing effect by prior treatment with ivermectin within the rotation protocol. The practical therapeutic compatibility between these 2 antiparasitics became obvious. Anoplocephala eggs were found in feces of some horses treated with IVM only, but no Anoplocephala eggs were found in post-treatment feces of horses treated on the alternation program.Strongyle larval cultures prepared as treatment pairs indicated high efficacy by ivermectin throughout the 2 years whether used alone or as a rotational drug, with improved cyathostome control by pyrantel pamoate. The combined use of EPG determinations and concurrent larval cultures in anthelmintic evaluations provide a greater spectrum of reliable results than from parasite egg counts alone.     

Cetirizine in horses: pharmacokinetics and effect of ivermectin pretreatment

The pharmacokinetics of the histamine H(1)-antagonist cetirizine and the effects of pretreatment with the antiparasitic macrocyclic lactone ivermectin on the pharmacokinetics of cetirizine were studied in horses. After oral administration of cetirizine at 0.2 mg/kg bw, the mean terminal half-life was 3.4 h (range 2.9-3.7 h) and the maximal plasma concentration 132 ng/mL (101-196 ng/mL). The time to reach maximal plasma concentration was 0.7 h (0.5-0.8 h). Ivermectin (0.2 mg/kg bw) given orally 1.5 h before cetirizine did not affect its pharmacokinetics. However, ivermectin pretreatment 12 h before cetirizine increased the area under the plasma concentration-time curve by 60%. The maximal plasma concentration, terminal half-life and mean residence time also increased significantly following the 12 h pretreatment. Ivermectin is an inhibitor of P-glycoprotein, which is a major drug efflux transporter in cellular membranes at various sites. The elevated plasma levels of cetirizine following the pretreatment with ivermectin may mainly be due to decreased renal secretion, related to inhibition of the P-glycoprotein in the proximal tubular cells of the kidney. The pharmacokinetic properties of cetirizine have characteristics which are suitable for an antihistamine, and this substance may be a useful drug in horses.     

Alternative antiparasitic treatment of horses with pyrantel pamoate suspension and ivermectin oral solution compared with horses treated only with ivermectin oral solution

A practical parasite control program was evaluated in a 2-year clinical trial using pyrantel pamoate suspension (PYR) and ivermectin oral solution (IVM) in a seasonal rotation program, in comparison with continued use of IVM given at 2-month intervals. At least 15 horses in each of 2 treatment groups were distributed over 8 locations. In the alternation program, IVM was given twice (October, December) during the botfly (Gasterophilus spp.) season and again in April to treat against the lighter botfly season and to kill existing Onchocerca microfilariae prior to heavy Culicoides swarming. Pyrantel was given in February, June and August to continue suppression of strongyle infections and to treat against potentially developing Anoplocephala infections. In the program of IVM continuous use, the drug was given on the same schedule as either treatment on the alternation program.The course of strongyle infections was monitored by fecal sample analyses (EPG) at semimonthly intervals and by larval cultures of treatment pairs prepared at each treatment interval (alternation program) or at 4-month intervals (continuous IVM program). The strongyle egg count numbers were reduced to zero by the first IVM treatment, increased only slightly by the next treatment at 2 months, and repeated the reduced pattern with each treatment for 2 years. The alternation program in the first year had typical responses to each drug: IVM reducing strongyle EPG counts to zero which increased slightly at 2 months, followed by the PYR treatment, which reduced the strongyle egg counts for 4 weeks with rebound at 6 and 8 weeks. At the end of the first year and into the second, the IVM treatments of October and December established a zero or low strongyle EPG pattern which continued through the spring with PYR and IVM treatments. The second summer PYR treatments then maintained far better cyathostome control than had been reported for this drug. There may be a complementary or enhancing effect by prior treatment with ivermectin within the rotation protocol. The practical therapeutic compatibility between these 2 antiparasitics became obvious. Anoplocephala eggs were found in feces of some horses treated with IVM only, but no Anoplocephala eggs were found in post-treatment feces of horses treated on the alternation program.Strongyle larval cultures prepared as treatment pairs indicated high efficacy by ivermectin throughout the 2 years whether used alone or as a rotational drug, with improved cyathostome control by pyrantel pamoate. The combined use of EPG determinations and concurrent larval cultures in anthelmintic evaluations provide a greater spectrum of reliable results than from parasite egg counts alone.     

伊维菌素在樱桃谷鸭体内证治药物动力学研究

本试验利用证治药动学的方法,研究了伊维菌素在樱桃谷鸭体内药物动力学变化,旨在验证黄曲霉毒素B1中毒后中药制剂＂保肝护肾脱霉素＂的药理作用。将117只健康1日龄的樱桃谷鸭随机平均分成3组,Ⅰ组（正常组）饲喂健康饲料,饲喂28d。Ⅱ组（病理组）前7d饲喂健康饲料,8-21d饲喂含有黄曲霉毒素B1的霉变饲料,22-28d饲喂健康饲料。Ⅲ组（中药反证组）前7d饲喂健康饲料,8-22d饲喂含黄曲霉毒素B1的霉变饲料,22-28d饲喂健康饲料,与此同时对每只鸭子每天口服保肝护肾脱毒素液5mL,口服7d,第29天,给上述3组试验鸭口服伊维菌素溶液,分别在给药前（0h）和给药后时间点从鸭的颈静脉采血,采用高效液相荧光色谱法进行检测。结果显示,黄曲霉毒素B1造成的病理损伤,能改变伊维菌素内服在鸭体内的药动学特征,表现出吸收减慢,吸收程度减弱,消除速率减弱的药动学特征。经过中药制剂＂保肝护肾脱霉素＂反证后,伊维菌素的吸收及消除速度都有不同程度地增加。试验结果表明,从药动学角度说明中药制剂＂保肝护肾脱霉素＂对黄曲霉毒素B1造成的病理损伤有修复作用。     

Fexofenadine in horses: pharmacokinetics, pharmacodynamics and effect of ivermectin pretreatment

The pharmacokinetics and the effects on inhibition of histamine-induced cutaneous wheal formation of the histamine H1-antagonist fexofenadine were studied in horse. The effect of ivermectin pretreatment on the pharmacokinetics of fexofenadine was also examined. After intravenous infusion of fexofenadine at 0.7 mg/kg bw the mean terminal half-life was 2.4 h (range: 2.0-2.7 h), the apparent volume of distribution 0.8 L/kg (0.5-0.9 L/kg), and the total body clearance 0.8 L/h/kg (0.6-1.2 L/h/kg). After oral administration of fexofenadine at 10 mg/kg bw bioavailability was 2.6% (1.9-2.9%). Ivermectin pretreatment (0.2 mg/kg, p.o.) 12 h before oral fexofenadine decreased the bioavailability to 1.5% (1.4-2.1%). In addition, the area under the plasma concentration-time curve decreased 27%. Ivermectin did not affect the pharmacokinetics of i.v. administered fexofenadine. Ivermectin may influence fexofenadine absorption by interfering in intestinal efflux and influx pumps, such as P-glycoprotein and the organic anion transport polypeptide family. Oral and i.v. fexofenadine significantly decreased histamine-induced wheal formation, with a maximal duration of 6 h. A pharmacokinetic/pharmacodynamic link model indicated that fexofenadine in horse has antihistaminic effects at low plasma concentrations (EC50 = 16 ng/mL). However, oral treatments of horses with fexofenadine may not be suitable due to the low bioavailability.     

Pharmacokinetics,metabolism and excretion of celecoxib,a selective cyclooxygenase‐2 inhibitor,in horses

Celecoxib, a nonsteroidal anti‐inflammatory drug, is frequently used to treat arthritis in humans with minimal gastrointestinal side effect compared to traditional NSAIDs. The primary aim of this study was to determine the pharmacokinetic profile of celecoxib—a selective cyclooxygenase‐2 (COX‐2) inhibitor in horses. Six horses were administered a single oral dose of celecoxib at 2 mg/kg (body weight). After oral dosing, the drug reached a maximum concentration (mean ± SD) in blood of 1,088 ± 324 ng/ml in 4.58 hr. The elimination half‐life was 13.60 ± 3.18 hr, and the area under the curve was 24,142 ± 1,096 ng hr ml^?1. The metabolism of celecoxib in horses was via a single oxidative pathway in which the methyl group of celecoxib is oxidized to a hydroxymethyl metabolite and is further oxidized to form a carboxylic acid metabolite. Celecoxib is eliminated mainly through faeces as unchanged drug and as metabolites in urine. Therefore, instructions for a detection time following therapeutic dosing of celecoxib can be set by the racing practitioner and veterinarians to control illegal use in horse racing based on the results of this study.     

Pharmacokinetics of single doses of maropitant citrate in adult horses

The neurokinin‐1 (NK) receptor antagonist, maropitant citrate, mitigates nausea and vomiting in dogs and cats. Nausea is poorly understood and likely under‐recognized in horses. Use of NK‐1 receptor antagonists in horses has not been reported. The purpose of this study was to determine the pharmacokinetic profile of maropitant in seven adult horses after single intravenous (IV; 1 mg/kg) and intragastric (IG; 2 mg/kg) doses. A randomized, crossover design was performed. Serial blood samples were collected after dosing; maropitant concentrations were measured using LC‐MS/MS. Pharmacokinetic parameters were determined using noncompartmental analysis. The mean plasma maropitant concentration 3 min after IV administration was 800 ± 140 ng/ml, elimination half‐life was 10.37 ± 2.07 h, and volume of distribution was 6.54 ± 1.84 L/kg. The maximum concentration following IG administration was 80 ± 40 ng/ml, and elimination half‐life was 9.64 ± 1.27 hr. Oral bioavailability was variable at 13.3 ± 5.3%. Maropitant concentrations achieved after IG administration were comparable to those in small animals. Concentrations after IV administration were lower than in dogs and cats. Elimination half‐life was longer than in dogs and shorter than in cats. This study is the basis for further investigations into using maropitant in horses.     

Comparative pharmacokinetic and pharmacodynamic response of single and double intraruminal doses of ivermectin and moxidectin in nematode-infected lambs

Abstract

AIMS: To compare the pharmacokinetics, distribution and efficacy (pharmacodynamic response) of intraruminal ivermectin (IVM) and moxidectin (MXD) administered at 0.2 and 0.4?mg/kg to naturally nematode-infected lambs, and to determine the ex vivo accumulation of these anthelmintics by Haemonchus contortus.

METHODS: Romney Marsh lambs, naturally infected with IVM-resistant H. contortus, were allocated to treatment groups based on faecal nematode egg counts. They received 0.2 or 0.4?mg/kg IVM or MXD (n=10 per group), or no treatment (Control; n=6), on Day 0. Samples from four animals from each treatment group, including abomasal parasites, were obtained on Day 1. Plasma samples were also collected from Day 0 to 14, and a faecal egg count reduction test (FECRT) and a controlled efficacy trial were carried out on Day 14. Concentrations of IVM and MXD in plasma, in abomasal and intestinal tissues and in H. contortus were evaluated by high-performance liquid chromatography. Additionally, the ex vivo drug accumulation of IVM and MXD by H. contortus was determined.

RESULTS: Peak plasma concentrations and the area under the concentration vs. time curve for both IVM and MXD were higher for 0.4 than 0.2?mg/kg treatments (p<0.05), but there were no differences for other parameters. Concentrations of IVM and MXD in the gastrointestinal target tissues and in H. contortus were higher compared to those measured in plasma. Concentrations of both drugs in H. contortus were correlated with those observed in the abomasal content (r=0.86; p<0.0001). The exposure of H. contortus to IVM and MXD was related to the administered dose. Mean FECRT and efficacy for removal of adult H. contortus was 0% for IVM at 0.2 and 0.4?mg/kg. For MXD, FECRT were >95% for both treatments, and efficacy against H. contortus was 85.1% and 98.1% for 0.2 and 0.4?mg/kg, respectively. The ex vivo accumulation of IVM and MXD in H. contortus was directly related to the drug concentration present in the environment and was influenced by the duration of exposure.

CONCLUSION: Administration of IVM and MXD at 0.4 compared with 0.2?mg/kg accounted for enhanced drug exposure in the target tissues, as well as higher drug concentrations within resistant nematodes. The current work is a further contribution to the evaluation of the relationship between drug efficacy and basic pharmacological issues in the presence of resistant parasite populations.     

An ivermectin tablet for sheep: Efficacy against gastro-intestinal nematodes and a bioavailability comparison with a liquid ivermectin formulation

An ivermectin tablet for o ral administration to sheep was developed for use in countries where it is customary to treat sheep with anthelmintic tablets. Tablets require no special administration equipment, and offer convenience for storage and transport. The ivermectin tablet, which delivers 10 mg of ivermectin (200 μg kg⁻¹ in a 50 kg sheep), had similar bioavailability to a liquid formulation of ivermectin (IVOMEC^® Liquid for Sheep) as determined by peak plasma ivermectin concentrations and area under the concentration curve in plasma (P>0.10). In dose confirmation trials in which nematode infections were induced in helminth-naive sheep, animals treated with the ivermectin tablet had significantly fewer adult and fourth-stage larval nematodes than untreated control sheep P<0.01 with efficacies >99% against all nematode species tested. In six field trials evaluating the efficacy of the ivermectin tablet in 240 Merino sheep, the reductions in faecal nematode egg counts ranged between 98 and 100%, as determined by comparison of pre- and post-treatment counts for the ivermectin-treated group.     

Intravenous tramadol: effects, nociceptive properties, and pharmacokinetics in horses

ObjectiveTo determine the optimal dose, serum concentrations and analgesic effects of intravenous (IV) tramadol in the horse.Study designTwo-phase blinded, randomized, prospective crossover trial.AnimalsSeven horses (median age 22.5 years and mean weight 565 kg).MethodsHorses were treated every 20 minutes with incremental doses of tramadol HCl (0.1–1.6 mg kg^?1) or with saline. Heart rate, respiratory rate, step frequency, head height, and sweating, trembling, borborygmus and head nodding scores were recorded before and up to 6 hours after treatment. In a second study, hoof withdrawal and skin twitch reflex latencies (HWRL and STRL) to a thermal stimulus were determined 5 and 30 minutes, and 1, 2, 4 and 6 hours after bolus IV tramadol (2.0 mg kg^?1) or vehicle. Blood samples were taken to determine pharmacokinetics.ResultsCompared to saline, tramadol caused no change in heart rate, step frequency or sweating score. Respiratory rate, head height, and head nodding and trembling scores were transiently but significantly increased and borborygmus score was decreased by high doses of tramadol. Following cumulative IV administration of 3.1 mg kg^?1 and bolus IV administration of 2 mg kg^?1, the elimination half-life of tramadol was 1.91 ± 0.33 and 2.1 ± 0.9 hours, respectively. Baseline HWRL and STRL were 4.16 ± 1.0 and 3.06 ± 0.99 seconds, respectively, and were not significantly prolonged by tramadol.Conclusion and clinical relevanceIV tramadol at cumulative doses of up to 3.1 mg kg^?1 produced minimal transient side effects but 2.0 mg kg^?1 did not provide analgesia, as determined by response to a thermal nociceptive stimulus.     

Antiparasitic activity of an ivermectin and praziquantel combination paste in horses

Modern anthelmintic use in horses has decreased the prevalence of the large strongyles, which has in turn shifted the focus of parasitologists to the pathogenic importance of the small strongyles, tapeworms, and other parasites. These studies show that a combination product containing ivermectin and praziquantel allowed efficacious treatment of horses for nematode, cestode, and bot infections. The use of this combination product may be of special benefit to horses that are mainly kept outdoors and on grazing pastures.     

Postoperative pharmacokinetics of meloxicam in horses after surgery for colic syndrome

NSAID s are often used in horses with colic syndrome during the postoperative period, due to their ability to contrast endotoxemia and to promote an analgesic and anti‐inflammatory effect. As the pharmacokinetics of a drug are often modified in unhealthy animals compared to healthy subjects, the aim of this study was to evaluate the pharmacokinetic profile of meloxicam after i.v. administration in horses undergoing laparotomy for colic syndrome. Eight horses received 0.6 mg/kg of meloxicam i.v. towards the end of surgery. Blood samples were taken at scheduled time points during the following 24 hr. The serum concentration of the drug was determined by HPLC . Terminal half‐life (6.88 ± 2.96 hr), volume of distribution at steady‐state (186.53 ± 61.20 ml/Kg) and clearance (27.91 ± 5.72 ml kg^?1 hr^?1) were similar to those reported in literature for healthy horses. This result suggests that no adjustment of the approved dose should be necessary when meloxicam is used to treat horses in the immediate postoperative period after surgery for colic syndrome.     

敌百虫和伊维菌素对近邻剑水蚤的急性毒性

鱼苗孵化用水经常会滋生桡足类,严重影响育苗的成活率。本文通过水生生物急性毒性试验方法,研究敌百虫和伊维菌素对淡水常见桡足类近邻剑水蚤（Cyclops vicinus）的急性毒性。根据预试验的结果,敌百虫浓度梯度设置为0.3、0.6、1.2、2.4、4.8 mg/L,伊维菌素浓度梯度设置为0.01、0.04、0.16、0.64、2.56μg/L。每个浓度组设置3个平行,每个平行放10只桡足类,试验在20℃光照培养箱中进行。结果表明,敌百虫对桡足类的24 h LC50和48 h LC50分别为1.862、1.183 mg/L,而伊维菌素对桡足类的24 h LC50和48 h LC50分别为0.404μg/L、0.1644μg/L。伊维菌素的毒性远远大于敌百虫,生产上选用伊维菌素效果更好。与此同时,敌百虫和伊维菌素对桡足类的安全浓度分别为0.1432 mg/L、0.00816μg/L,可以为生物监测环境农药污染提供重要依据。     

Plasma pharmacokinetics and faecal excretion of ivermectin (Eqvalan paste) and doramectin (Dectomax, 1%) following oral administration in donkeys

Ivermectin (IVM- Eqvalan paste, 1.87%) and doramectin (DRM-Dectomax 1%) were each administered orally to donkeys at 200 microgkg(-1) bodyweight. Blood and faecal samples were collected at predetermined times over 30 days and plasma pharmacokinetics and faecal excretion determined. Maximum plasma concentrations (C(max)) of IVM (23.6 ngml(-1)) and DRM (33.9 ngml(-1)) were obtained at (t(max)) 19.2 and 24h, respectively. The area under the concentration curve (AUC) of DRM (228.9 ngdayml(-1)) was significantly larger than that of IVM (119.3 ngdayml(-1)) and mean residence time (MRT) was 6.5 days for IVM and 9.1days for DRM. The highest (dry weight) faecal concentrations (9.33 microgg(-1) - IVM, 12.12 microgg(-1) - DRM) were detected at 55.9 and 48.0 h, respectively and each compound was detected (0.05 microgg(-1)) in faeces between 11h and 9 days following oral administration in donkeys.     

Plasma pharmacokinetics and faecal excretion of ivermectin, doramectin and moxidectin following oral administration in horses

The present study was carried out to investigate whether the pharmacokinetics of avermectins or a milbemycin could explain their known or predicted efficacy in the horse. The avermectins, ivermectin (IVM) and doramectin (DRM), and the milbemycin, moxidectin (MXD), were each administered orally to horses at 200 microg/kg bwt. Blood and faecal samples were collected at predetermined times over 80 days (197 days for MXD) and 30 days, respectively, and plasma pharmacokinetics and faecal excretion determined. Maximum plasma concentrations (Cmax) (IVM: 21.4 ng/ml; DRM: 21.3 ng/ml; MXD: 30.1 ng/ml) were obtained at (tmax) 7.9 h (IVM), 8 h (DRM) and 7.9 h (MXD). The area under the concentration time curve (AUC) of MXD (92.8 ng x day/ml) was significantly larger than that of IVM (46.1 ng x day/ml) but not of DRM (53.3 ng x day/ml) and mean residence time of MXD (17.5 days) was significantly longer than that of either avermectin, while that of DRM (3 days) was significantly longer than that of IVM (2:3 days). The highest (dry weight) faecal concentrations (IVM: 19.5 microg/g; DRM: 20.5 microg/g; MXD: 16.6 microg/g) were detected at 24 h for all molecules and each compound was detected (> or = 0.05 microg/g) in faeces between 8 h and 8 days following administration. The avermectins and milbemycin with longer residence times may have extended prophylactic activity in horses and may be more effective against emerging and maturing cyathostomes during therapy. This will be dependent upon the relative potency of the drugs and should be confirmed in efficacy studies.     

Clinical trial of efficacy of ivermectin pour‐on against gastrointestinal parasitic nematodes in silvopasturing horses

The aim of this study was to assess, by a clinical trial, the efficacy of an ivermectin‐based pour‐on treatment against gastrointestinal parasitic nematodes in naturally infected horses using 2 groups of mature indigenous Pura Raza Galega grazing mares. Faecal and blood samples were collected individually over a 21 week period. Faeces were analysed by the coprological flotation, sedimentation and migration techniques. Changes in circulating blood cells were monitored over the study period. The administration of the ivermectin suppressed the eggelimination of ascarids and pinworms throughout the study and no strongyle‐eggs were observed in the treatment group between the 3rd and 10th weeks. The numbers of red cells increased significantly after the anthelmintic therapy, and a statistical reduction in circulating leucocytes was recorded. No side effects were observed. The pour‐on ivermectin formulation was highly successful against gastrointestinal nematodes and appears to be a useful therapeutic routine for large groups of horses.