Efficacy of ivermectin as an anthelmintic in leopard frogs.

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.     

Efficacy of ivermectin and moxidectin against Otostrongylus circumlitus and Parafilaroides gymnurus in harbour seals (Phoca vitulina)

Verminous bronchopneumonia caused by infection with Otostrongylus circumlitus and Parafilaroides gymnurus is an important cause of death during the rehabilitation of harbour seals (Phoca vitulina). During the winter of 2000/01, 35 juvenile harbour seals with severe clinical signs of verminous bronchopneumonia were treated with either 0.2 mg/kg ivermectin orally or 0.2 mg/kg moxidectin subcutaneously, and monitored for 30 days. The efficacy of the anthelmintics was determined by the pattern of larval excretion (Baermannisation) and the progress of the clinical signs. Both anthelmintics had reduced larval excretion by at least 99 per cent after 10 days, but the seals' rapid breathing rate and and dyspnoea returned to normal more quickly in the animals treated with moxidectin. The pharmacokinetics of the anthelmintics were determined by solid-phase extraction, and high-performance liquid chromatography with fluorescence detection. Moxidectin had a mean (sd) residence time of 9.04 (2.12) days compared with 4.83 (1.14) days for ivermectin.     

Plasma bile acid concentrations in response to feeding in peregrine falcons (Falco peregrinus).

A significant post-prandial increase of plasma bile acid concentration (PBAC) was observed in peregrine falcons (Falco peregrinus). In order to avoid physiological food-induced elevations in PBAC, which can complicate interpretation of plasma chemistry results in birds of prey, it is recommended that blood samples be obtained after a fasting period of at least 24 hours.     

Effect of dietary exposure to aflatoxin B1 on resistance of young chickens to organophosphate pesticide challenge

White leghorn chickens were placed on a diet containing 0, 1000, or 3000 ppb aflatoxin B1 for 7 weeks. At the end of that time, the birds were challenged orally with the organophosphate pesticide malathion. A malathion dose of 215 mg/kg resulted in significant clinical signs of cholinergic poisoning in 4/10, 5/10, and 8/10 birds fed 0, 1000, and 3000 ppb aflatoxin B1, respectively, and the chickens required antidotal atropine 40 min later. Activity of brain cholinesterase was significantly lower than control levels in all birds given this dose of malathion, with activities being 28% +/- 6, 21% +/- 2, and 15% +/- 2 of control values (Mean +/- standard error, N = 5) if fed 0, 1000, and 3000 ppb aflatoxin B1, respectively. Plasma cholinesterase values paralleled those of brain, with significantly more inhibition in samples from birds given 1000 and 3000 ppb aflatoxins with malathion. Brain and plasma cholinesterase activities in birds fed aflatoxins and given a dose of malathion below the threshold for cholinergic signs (125 mg/kg) were also lower than activities in birds given malathion alone. Although aflatoxin alone had no direct effect on the activities of these enzymes, it appears that this mycotoxin may contribute to the esterase inhibition that is a manifestation of the acute toxic effects of malathion in chickens.     

Serologic evidence of exposure of raptors to influenza A virus

Serum or plasma samples from raptors that prey or scavenge upon aquatic birds were tested by a commercially available blocking enzyme-linked immunosorbent assay for the evidence of antibodies to influenza A virus. Samples were taken from birds (n = 616) admitted to two rehabilitation centers in the United States. In addition, samples from 472 migrating peregrine falcons (Falco peregrinus) trapped on autumnal and vernal migrations for banding purposes were also tested. Only bald eagles were notably seropositive (22/406). One each of peregrine falcon, great horned owl (Bubo virginianus), and Cooper's hawk (Accipiter cooperi) from a total of 472, 81, and 100, respectively, were also positive. None of the turkey vultures (n = 21) or black vultures (n = 8) was positive. No clinical signs referable to avian influenza were seen in any bird at the time of capture. These data indicate that, among raptors, bald eagles do have exposure to influenza A viruses.     

Iohexol-based measurement of intestinal permeability in birds

Background: Iohexol has been successfully used as a marker to assess intestinal permeability in humans and various other mammals. The objective of this study was to evaluate the use of oral iohexol as an intestinal permeability marker in four anatomically and nutritionally diverse bird species. Methods: Three dosages (1 ml/kg, 2 ml/kg, 4 ml/kg) of iohexol (755 mg/ml) were administered orally to each six clinically healthy pigeons and chickens at two-week intervals. Iohexol plasma concentration was determined 45, 90 and 180 minutes after administration. A comparative study was performed by administering iohexol twice to each six clinically healthy cockatiels and falcons, and determining iohexol plasma concentration at 45 or 90 minutes after administration. Results: The recommended iohexol dosage for permeability testing in birds was determined to be 1 ml/kg. Median plasma iohexol concentrations were 27.77 µg/ml in pigeons, 12.97 µg/ml in chickens, 14.24 µg/ml in cockatiels, and 47.81 µg/ml in falcons, 45 minutes after this dosage was administered. At 90 minutes after administration, median plasma iohexol concentrations were 40.68 µg/ml in pigeons, 21.59 µg/ml in chickens, 32.03 µg/ml in cockatiels, and 55.96 µg/ml in falcons. Conclusions and clinical relevance: Oral iohexol was a safe and feasible marker for intestinal permeability assessment in birds. Further investigations are warranted to establish species-specific reference intervals in larger numbers of healthy birds, and to examine the use of iohexol as a permeability marker in birds with disorders associated with altered intestinal permeability.     

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.     

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.     

Ketoconazole increases the plasma levels of ivermectin in sheep

The parasiticide ivermectin and the antifungal drug ketoconazole are drugs that interact with P-glycoprotein. We have tested the ability of ketoconazole at a clinical dose to modify the pharmacokinetics of ivermectin in sheep. Lacaune lambs were administered with a single oral dose of ivermectin alone at 0.2mg/kg (n=5) or in combination with a daily oral dose of ketoconazole (10mg/kg) given for 3 days before and 2 days after the ivermectin (n=5). The plasma kinetics of ivermectin and its metabolite were followed over 15 days by HPLC analysis. Co-administration of ketoconazole induced higher plasma concentrations of ivermectin, leading to a substantial increase in the overall exposure of the animals to the drug. Ketoconazole did not reduce the production of the main ivermectin metabolite but it may rather act by inhibiting P-glycoprotein, and thus increasing the absorption of ivermectin. The use of a P-gp reversing agent such as ketoconazole could be useful tool to optimize antiparasitic therapy in the face of the worldwide development of anthelmintic resistance.     

Efficacy of ivermectin in the treatment of induced Parascaris equorum infection in pony foals

Eighteen pony foals inoculated with 1,500 +/- 109 infective Parascaris equorum eggs were given 0.02 ml of ivermectin vehicle (liquid)/kg of body weight, PO, (control); 0.2 mg of ivermectin paste/kg, PO; or 0.2 mg ivermectin liquid/kg, PO, on postinoculation day (PID) 28. Foals were euthanatized on PID 42, and the small intestinal contents were examined for P equorum larvae. The mean number of fourth-stage P equorum larvae in foals treated with ivermectin paste and liquid were 3.5 and 6, respectively. Significantly (P less than 0.01) higher mean numbers of larvae (1,250) were detected in foals treated with ivermectin vehicle. Larvae recovered from foals treated with ivermectin vehicle were of significantly (P less than 0.002) longer mean length than those from foals treated with ivermectin paste or liquid. Gross examination of lungs and liver revealed similar pathologic changes from the migration of P equorum in all foals. Adverse reaction to treatment was not observed.     

Pharmacokinetics of ivermectin in pregnant and nonpregnant sheep

The plasma kinetic profile of ivermectin during the last trimester of pregnancy was studied in ewes after a single subcutaneous administration of 0.2 mg/kg body weight (BW). Sheep were randomly distributed into two groups. Ewes in group 1 (control, n=6) were left unmated, whereas in group 2 (pregnant, n=6) ewes were estrus-synchronized and mated with rams. Both groups were housed under similar conditions of management and feeding. At 120 days of pregnancy, both groups were given a subcutaneous injection of 0.2 mg/kg BW of ivermectin. Blood samples were taken by jugular puncture according to a fixed protocol between 1 h and 40 days post-treatment. After plasma extraction and derivatization, samples were analyzed by high performance liquid chromatography with fluorescence detection. A computerized pharmacokinetic analysis was performed, and the data were compared by means of the Student t-test. The results showed that plasma concentrations of ivermectin remained longer in the pregnant than in the control group. The mean values of pharmacokinetic parameters C(max), t(max), and area under the concentration-time curve (AUC) were similar for both groups of sheep. The mean residence time (MRT) values for the pregnant group (8.8+/-1.4 days) were higher (P<0.05) than those observed in the control group (5.3+/-1.9 days). It can be concluded that pregnancy increases the residence time of ivermectin in the plasma of pregnant sheep when it is administered subcutaneously.     

Safety and efficacy of ivermectin against ear mites (Otodectes cynotis) in ranch foxes

Efficacy of ivermectin at a dosage of 0.2 mg/kg of body weight was evaluated against naturally acquired ear mite (Otodectes cynotis) infestation in commercially raised ranch foxes (Vulpes fulva). Efficacy of ivermectin given sc twice at 3-week intervals was 97.4%. Toxicosis associated with drug treatment was not observed. Increased dosage of 1.0 mg/kg was given sc to 5 foxes each week for 6 consecutive weeks, and signs of toxicosis or illness were not observed after treatment.     

Plasma chemistry reference values in hybrid falcons in relation to their species of origin

Twenty-one blood chemistry parameters were determined in 127 peregrine falcons (Falco peregrinus), 79 gyr-peregrine hybrids and 166 gyr-saker hybrids. These parameters, together with those previously established in 53 gyr falcons (Falco rusticolus) and 234 saker falcons (Falco cherrug), were compared. There were statistically significant differences in 15 of the parameters between the saker and peregrine falcons; the saker and gyr falcons; the saker and gyr-saker hybrids; the peregrine and gyr falcons; and the peregrine and gyr-peregrine hybrids, but not between the gyr falcons and the gyr-saker falcon hybrids.     

Plasma enzyme activities indicative of liver cell damage in laying fowl given a diet containing 20 per cent of rapeseed meal

The effects of a diet containing a high proportion of rapeseed meal on the activity of certain plasma enzymes were studied in laying birds. The enzymes studied were alkaline phosphatase (AP), aspartate transaminase (AST), L-gamma-glutamyl-transferase (gamma-GT), isocitrate dehydrogenase (ICDH), leucine arylamidase (LAP), malate dehydrogenase (MDH) and sorbitol dehydrogenase (SDH). No notable differences were observed between the plasma AP, LAP or SDH activities of the birds given the rapeseed meal and the birds receiving a soyabean meal control diet throughout the experiment. However, the plasma AST and gamma-GT activities of the treated birds showed slight elevations while their plasma ICDH and MDH activities showed more marked elevations, which are indicative of liver damage, in response to the diet. Macroscopic observations of the livers of the birds at the end of the experiment were in fairly good accord with the elevation in plasma ICDH and MDH activities noted for the individual birds.     

The curative and antioxidative efficiency of ivermectin and ivermectin + vitamin E-selenium treatment on canine <Emphasis Type="Italic">Sarcoptes scabiei</Emphasis> infestation

The objective of the present study was to investigate the curative and antioxidative efficacy of ivermectin and ivermectin + vitamin E-selenium, and the influence of these agents on oxidative stress parameters in canines infested by Sarcoptes scabiei. Twenty two sarcoptic mites infested dogs and nine healthy dogs of 6 months to 2 years of age were divided into three groups. Group I comprised of healthy dogs (n = 9) whereas animals in group II (n = 11) and III (n = 11) were positive for scabies. Group II animals were treated with only 1% ivermectin @ 0.2 mg/kg SC whereas group III were additionally treated with Vitamin E and selenium (tocopherol 50 mg + Se 1.5 mg/ml) @0.5 ml/20 kg IM at weekly intervals for three times. Blood samples were collected on day 0 and 28 post therapy. The values for hemato-biochemical parameters and activities of antioxidant enzymes were significantly decreased (P < 0.05) whereas level of lipid peroxidation was significantly increased in all the infested dogs in comparison to the healthy dogs on day 0 which approached normalcy by day 28 post therapy. The dogs of group III showed better clinical recovery in comparison to group II at the end of therapy. Thus, administration of vitamin E and selenium in addition to standard therapy can alleviate these alterations hastening the clinical recovery of diseased dogs and can be recommended as an adjunct therapy with miticides for canine sarcoptic mange.     

Central and peripheral neurotoxic effects of ivermectin in rats

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.     

A possible relationship between bumblefoot responsive to potassium arsenite and micrococci in the blood of three birds of prey

Pododermatitis (bumblefoot) is a major health problem of falcons world-wide because healing processes in the talons are difficult and lengthy. A peregrine (Falco peregrinus), a merlin (Falco columbarius) and a saker falcon (Falco cherrug) with bumblefoot at different stages ranging from III to V, were all found to be carriers of micrococcus-like organisms in the blood and two of them were successfully treated with 0.5% potassium arsenite in low dosage given intravenously. A number of considerations are made on the immune dysfunction aspects of bumblefoot in birds of prey and on the emerging role of arsenic-based medicaments in the treatment of animal and human immune dysfunction syndromes.     

Anthelmhntic effects of injectable and oral paste formulations of ivermectin against 28-day infections of parascaris equorum

Efficacy of ivermectin treatment (0.2 mg/kg) against 28-day experimental infections of Parascaris equorum was determined in 18 pony foals6–17.5 weeks old. There were 6 foals in each group: nontreated control, ivermectin injectable or oral paste. In comparison with larvae found in the nontreated controls, ivermectin injectable or paste was 96.0% and 99.9% efficacious. There was a distinct difference in drug effect against the larger (ca 26mm.) vs the smaller (13–19mm) larvae by the 2 formulations of ivermectin. There were no adverse signs related to treatment of the young foals.     

伊维菌素泼背剂对牦牛寄生虫的驱除效果试验

为选择适应于高寒牧区放牧牦牛大群驱除体内外寄生虫的理想荆型,在青海大通种牛场通过粪检选60头牦牛,随机分为3组,每组20头,试验1组用伊维菌素泼背荆接0.5 mg/kg体重剂量经背部皮肤浇泼给药,试验2组用伊维菌素注射剂按0.2 mg/kg体重剂量经皮下注射给药,试验3组为空白对照组.分析了三组不同寄生虫卵转率、虫卵减少率及驱虫率指标的变化,同时对药物的安全性进行了观察.结果试验1组消化道线虫虫卵转阴率、减少率分别为90%和99.1%,原圆科线虫幼虫转阴率、减少率分别为80%和92.8%;线虫成虫、寄生阶段幼虫的总计驱虫率分别为99.3%和98.8%;试验2组相应指标分别为90%和98.7%、80%和92.9%、99.4%和99.2%;1.2组对牛颚虱杀虫率均达100%,但对莫尼茨绦虫无效,对照组体内外寄生虫均无明显变化.表明伊维菌素泼背剂0.5 mg/kg剂量安全,驱虫效果可信,可在青海高寒地区牦牛体内外寄生虫驱虫工作中推广应用.     

The normal electrocardiogram of the unanesthetized peregrine falcon (Falco peregrinus brookei)

The mean duration and amplitudes of the lead II electrocardiogram were determined in the peregrine falcon (Falco peregrinus brookei) using 10 birds ranging in age from 1 to 5 yr. Electrocardiograms were performed on unanesthetized falcons in order to avoid the anesthesia effect on the electrocardiogram, by a method which seems to induce a tonic immobility-like reaction. All the falcons had a normal sinus rhythm, with a mean heart rate of 268 beats per minute. Mean durations of PR, ST, QT, and RR intervals were higher (but not statistically significant) in females than in males, except for the ST segment, with similar values in both sexes. P-wave deflections were positive in I, II, III, aVL, and aVF and negative in aVR. The normal patterns of wave forms of the QRS complexes in all leads were of QS and rS types, except for aVR and aVL, which presented an R configuration. The mean electrical axis was negative, with an average of -99.9 degrees. T-wave deflections were positive in I, II, III, and aVF leads II and negative in aVR and aVL. The data collected in this study may serve as a guide for electrocardiographic monitoring of peregrine falcons.