Review of monensin toxicosis in horses

Results of experimental studiesindicate that horses are much more sensitive to monensin toxicity than cattle. Single dose studies by gavage with mycelial monensin resulted in an estimated LD₅₀ of 1.38 mg/kg of body weight. Subacute feeding studies indicate that horses will tolerate the highest use level for cattle of 33 ppm without any evidence of toxicity. Evidence of intoxication was apparent with the highest use level for chickens of 121 ppm.In pasture supplement studies, horses ate supplement containing high levels of nonensin upon initial exposure which resulted in toxicity and/or death. Following initial exposure to sublethal levels, consumption of monensin containing supplements was negligible.The clinical signs of toxicity includedpartial to complete anorexia, colicky pain, sweating and tachycardia, uneasiness, polyuria, progressive ataxia, recumbency with frequent attempts to rise and thrashing of the limbs followed by death. Examination at necropsy of animals that die soon after initial exposure to monensin may show no significant lesions, otherwise hemorrhage and pale areas in the heart with transudation into body cavities may be seen. Evidence of degenerative cardiomyopathy and congestive heart failure may be observed on histopathologic examination. Increased activities of muscle origin enzymes may also be found.The results of controlled studiesand evidence from field reports indicated that the greatest risk of intoxication was upon initial exposure to feed or supplement containing monensin. Feed mistakes and mixing errors were the two most common causes of monensin toxicity in field cases.     

Long‐term assessment of horses and ponies post exposure to monensin sodium in commercial feed

Reasons for performing study: Acute monensin intoxication in equids is well described; however, the long‐term effects of sublethal intoxication and ability to return to previous use are less well understood. Long‐term observations may allow improved estimation of prognosis in cases of sublethal intoxication. Objectives: To assess horses and ponies exposed to sublethal amounts of monensin for evidence of chronic sequelae and ability to return to prior/intended use. Methods: Twenty‐nine horses and 8 ponies were assessed utilising serum biochemistry, treadmill exercise stress testing, electrocardiography, and pre‐ and post exercise echocardiography ≥6 weeks after ingestion of monensin‐contaminated feed. Animals with evidence of monensin‐induced cardiomyopathy were re‐examined after a period of rest of ≥11 months. Follow‐up information was obtained by owner telephone interview ≥52 months after exposure. Results: During resting echocardiography, 11 animals had reduced/low‐normal left ventricular fractional shortening (FS); an increase in FS in 8 of these animals was measured ≥11 months later. Six animals had reduced or low‐normal FS during post exercise echocardiography. Two horses had ventricular premature depolarisations during exercise. Follow‐up information was available for 35 animals: 21 returned to athletic/reproductive use, 13 were retired immediately and one died. Mean FS increased significantly (P<0.001) between initial and second examination in 15 animals that underwent resting echocardiography on 2 occasions. Conclusions: Some equids exposed to sublethal doses of monensin may not develop permanent myocardial disease and a return to athletic/reproductive use is possible. Potential relevance: Exercise stress testing, echocardiography and electrocardiography may be useful for detection and monitoring of cardiac dysfunction in equids exposed to monensin and determining whether a return to athletic/reproductive use is possible.     

Pyrrolizidine alkaloid-induced liver disease in horses: an early diagnosis

Nine adult horses were fed alfalfa hay cubes containing approximately 10% Senecio vulgaris until all horses had consumed approximately the same amount of toxic components of S vulgaris, pyrrolizidine alkaloids (PA). The amount of PA consumed was determined by the amount that induced clinical signs of PA toxicosis in 3 horses. The 6 other horses were given similar amounts per kilogram of body weight. An initial decrease of feed intake was observed when horses' diets were changed from alfalfa cubes to alfalfa/Senecio cubes, and feed intake was decreased further over 89 to 98 days. From 50 to 159 days, body weight decreased in all horses. Liver disease was induced in all 9 horses after they ate an average of 233 +/- 9.2 mg of PA/kg of body weight. Eight horses died or were euthanatized. Treatment with branched chain amino acids had no effect on mortality, but appeared to reduce neurologic problems. Clinical signs of PA-induced liver disease included ataxia, head pressing, and decreased feed intake. Other clinical signs of toxicosis were observed individual horses, but did not develop in most horses. Megalocytic hepatopathy developed. Liver abnormalities proceeded as PA was consumed and were severe in 8 of 9 horses before clinical signs of toxicosis appeared. Sulfobromophthalein sodium clearance did not decrease until PA-induced liver disease was advanced. Bile acid (BA) concentrations increased to greater than or equal to 50 mumol/L, in the 8 horses that died. One horse had hepatopathy and increased BA concentration, but survived. In this horse, BA concentration peaked at 33 mumol/L and then decreased.(ABSTRACT TRUNCATED AT 250 WORDS)     

Control of bovine coccidiosis with monensin: in nonresistant newborn calves

Newborn Holstein male calves were purchased within 3 days after birth and were removed from the local farms to the Dixon Springs Agricultural Research Center. They were hand-fed for 7 weeks and then weaned to a prepared feed. Eight groups, each of 4 calves, were housed in separate pens. In each of 4 pens (pens 2 to 5), 1 calf was inoculated with sporulated oocysts of Eimeria bovis (and was not medicated); 1 calf was inoculated and given feed with added monensin at the dosage level of 10 g/906 kg of feed; and 2 calves were inoculated and given medicated feed with added monensin at the dosage level of 20 g/906 kg or 30 g/906 kg. In the 4 other pens (6 to 9), the calves were inoculated with E zuernii and otherwise were given feed without or with added monensin as in pens 2 through 5. Another group of 5 calves (all kept in 1 pen), served as noninoculated, nonmedicated controls. At 14 days after inoculations with E bovis, the single calves in each of the 4 pens that were given the nonmedicated feed began to show clinical signs of coccidiosis and discharged increasing numbers of oocysts. The other inoculated calves (given monensin) had fewer clinical signs and discharged fewer oocysts in the feces as the level of medication in the feed increased. The calves inoculated with E zuernii developed only moderately severe infections when compared with those inoculated with E bovis. Inoculated (with E bovis) nonmedicated calves had severe reductions in feed consumption and weight, and 3 of 4 died.(ABSTRACT TRUNCATED AT 250 WORDS)     

Ionophores alter hepatic concentrations of intermediary carbohydrate metabolites in steers

The effects of ionophores on liver weight and function were determined in finishing steers (n = 24; avg weight 440 kg). Steers were group-fed one of three treatments (control, lasalocid or monensin at 33 mg/kg feed) for 46 d prior to slaughter. Three days prior to slaughter, blood was collected for the determination of serum Ca and Mg. At slaughter, the liver was removed, weighed, sampled, frozen in liquid nitrogen and subsequently analyzed for concentrations of carbohydrate metabolites and minerals. Liver weight (5.9 kg) was unaffected by treatment. Serum and hepatic Ca and Mg were not affected by ionophore treatment. Hepatic glycogen levels in steers fed ionophores were unaffected by treatment. Fructose 1,6-bisphosphate was 21% lower (P less than .10) in hepatic tissue of steers fed ionophores, whereas dihydroxyacetone phosphate was 15 to 37% greater in hepatic tissue of steers fed monensin (P less than .20) or lasalocid (P less than .10). Glyceraldehyde 3-phosphate was elevated more extensively by lasalocid than by monensin with increases of 72 (P less than .05) and 132% (P less than .001), respectively, over controls. Glycerol 3-phosphate levels were 37% (P less than .05) and 12% (NS) greater with these ionophores. Hepatic levels of pyruvate were elevated 12 (NS) to 36% (P less than .17) for monensin and lasalocid. Fructose 2,6-bisphosphate levels were 25% lower (P less than .25) in hepatic tissue of steers fed ionophores than in hepatic tissue from control steers. Other metabolites of carbohydrate metabolism in hepatic tissue were not altered appreciably. Changes in levels of intermediary metabolites of carbohydrate metabolism suggest alterations in hepatic carbohydrate metabolism favoring gluconeogenesis in steers fed ionophores.     

Comparison of the oral bioavailability and tissue disposition of monensin and salinomycin in chickens and turkeys

Henri, J., Maurice, R., Postollec, G., Dubreil‐Cheneau, E., Roudaut, B., Laurentie, M., Sanders, P. Comparison of the oral bioavailability and tissue disposition of monensin and salinomycin in chickens and turkeys. J. Vet. Pharmacol. Therap.  35 , 73–81. The current study describes the pharmacokinetic parameters of two carboxylic polyether ionophores: monensin in turkeys and salinomycin in chickens. These data can be used to understand and predict the occurrence of undesirable residues of coccidiostats in edible tissues of these animal species. Special attention is paid to the distribution of residues between the different edible tissues during and at the end of the treatment period. For the bioavailability studies, monensin was administered to turkeys intravenously, in the left wing vein, at a dose of 0.4 mg /kg and orally at a dose of 20 mg /kg. Salinomycin was administered to chickens intravenously, in the left wing vein, at a dose of 0.25 mg /kg and orally at a dose of 2.5 mg /kg. Residue studies were carried out with supplemented feed at the rate of 100 mg /kg of feed for monensin in turkeys and 70 mg /kg for salinomycin in chickens, respectively. Coccidiostats had a low bioavailability in poultry (around 30% for monensin in chickens, around 1% for monensin in turkeys and around 15% for salinomycin in chickens). Monensin in chickens had a longer terminal half‐life (between 3.07 and 5.55 h) than both monensin in turkeys (between 1.36 and 1.55 h) and salinomycin in chickens (between 1.33 and 1.79 h). The tissue /plasma partition coefficients showed a higher affinity of both monensin and salinomycin for fat, followed by liver and muscle tissue. The depletion data showed a fairly rapid elimination of coccidiostats in all the tissues after cessation of treatment. According to the results of depletion studies, a withdrawal period of 1 day seems sufficient to avoid undesirable exposure of consumers.     

Effect of dental correction on voluntary hay intake,apparent digestibility of feed and faecal particle size in horse

Summary In nine adult Warmblood horses with mild to moderate dental findings (no signs of discomfort during chewing), voluntary hay intake before and after dental correction was examined. In a second experiment, digestibility of feed and faecal particle size were determined (3 days of total faecal collection) before and after dental correction. During both digestion trials including a 3‐day adaptation period, the amount of hay and concentrate (mixture of oats, barley and maize) was kept constant in each individual horse before and after dental correction. Voluntary hay intake in individual horses ranged from 11 to 22 g DM/kg BW/day and did not differ before and after dental treatment. Apparent digestibility of DM, energy, crude fibre and Nfe increased significantly after dental correction (energy digestibility before dental correction 46.8 ± 7.4%, after dental correction 51.5 ± 8.5%). Apparent digestibility of feed was higher in horses eating more concentrates than in those eating less concentrates. Improvement of digestibility was more marked in horses eating larger amounts of grain. There was no relationship between severity or type of dental alterations and improvement of apparent feed digestibility. Dental correction had no effect on faecal particle size.     

Effects of supplemental feed with or without ionophores on lambs and Angora kid goats on rangeland

Effects of supplemental feed and of ionophore concentration in supplemental feed on gastrointestinal rate parameters, forage intake and weight gain were measured in individually supplemented grazing lambs and Angora kid goats. The 12 dietary treatments included negative control (NC; grazed forage only), positive control (PC; grazing plus 13.6 g supplement DM/kg.75), and PC plus monensin or lasalocid, each at 33, 66, 99, 132 or 165 mg/kg in the supplement. Gastrointestinal fill, retention time, turnover rate and fecal output were estimated by applying a single-compartment model to the fecal excretion of a single dose of ytterbium. Forage digestibility was estimated from forage and fecal concentrations of indigestible fiber. Supplemental feed increased digestibility of forage and total intake in sheep but had no effect on forage intake. In goats, supplemental feed did not increase digestibility of forage but decreased forage intake. Supplemental feed increased weight gain in both species. Increasing the monensin concentration in supplemental feed reduced supplement intake greatly in sheep and slightly in goats. Lasalocid did not affect intake of supplement by either sheep or goats. Overall, ionophores had minimal effects on the response criteria. Because feed intake and digestibility were not affected, any increase in gain or efficiency in lambs or kid goats on rangeland from consumption of ionophores must be a result of their therapeutic value or of improved physiological efficiency.     

Evaluation of lasalocid as a coccidiostat in calves: titration, efficacy, and comparison with monensin and decoquinate

Two experiments were conducted to evaluate lasalocid as a coccidiostat in Holstein calves and to compare lasalocid with monensin and decoquinate. In experiment 1, calves in 3 groups (6 calves/group) were each inoculated with 500,000 sporulated oocysts, 88% of which were Eimeria bovis and 12% were E zuernii. Calves in each group were given lasalocid-medicated feed at 0.50 (group 3), 0.75 (group 4), or 1 mg/kg (group 5) of body weight/day for 45 days. Two control groups (6 calves/group) were also evaluated; calves in control group 2 were inoculated and nontreated, and calves in control group 1 were noninoculated and nontreated. At 0.50, 0.75, or 1 mg/kg/day, lasalocid was equally effective in preventing induced coccidiosis (E bovis and E zuernii) in calves. Compared with inoculated nontreated controls, treated calves had significantly (P less than 0.05) fewer oocysts in feces and had fewer clinical signs of coccidiosis from days 16 to 30 after inoculation. Experiment 2 was conducted to compare the effectiveness of monensin, lasalocid, and decoquinate for the prevention of experimentally induced coccidiosis. Calves (n = 48) were allotted into 4 groups (12 calves/group); each was inoculated orally with 275,000 sporulated oocysts, predominantly E bovis and E zuernii, and each was given nonmedicated feed (group 6) or feed medicated with 33 mg of lasalocid (group 7), decoquinate (group 8), or monensin (group 9)/kg of feed for 46 days. Calves given medicated rations had significantly (P less than 0.05) fewer oocysts in their feces and fewer clinical signs of coccidiosis than did calves given nonmedicated rations.(ABSTRACT TRUNCATED AT 250 WORDS)     

Ionophore taste preferences of dairy heifers

Two taste preference studies were conducted using six Holstein heifers in each experiment to determine preferences for no ionophore, lasalocid, or monensin in the diet. In Exp. 1, individually penned (approx. 5 mo old; 220 +/- 14 kg BW) heifers were fed a basal total mixed ration containing 46% corn silage, 46% grass haylage, and 8% soybean meal (DM basis). There were five treatments (mg/kg BW(-1)*d(-1)): 0 ionophore (control), 1 lasalocid (1L), 2 lasalocid (2L), 1 monensin (1M), or 2 monensin (2M). Ionophores were provided as part of the mineral mix that had been added to the control diet and through an ionophore-grain by-product mix to make the 2L and 2M treatments. All five diets were offered for 7 d, with the first 2 d for adaptation and the last 5 d for measurement of feed intake. The most preferred diet was then removed and the study continued with the four remaining diets. The most preferred diets were again eliminated sequentially, so that only two diets remained on d 13 and 14. Each feeding segment ranking of treatment preferences was determined based on the weight of feed refused at the end of each feeding segment. In Exp. 2, six 6-wk-old heifers (75 +/- 5 kg of BW) were individually fed either 0, 1L, or 1M in a study similar to Exp. 1, except that the most preferred diet was removed after 4 d, with the first day for adaptation and the last 3 d for measurement of feed intake. In Exp. 1, orthogonal contrasts indicated that heifers preferred the 1L and 2L diets over the 1M and 2M diets. Preferences between diet concentrations of ionophores (1 and 2 mg/kg of BW; Exp. 1) and the control and ionophore treatments did not differ, nor was there an interaction between ionophores and their concentration. Dairy heifers previously fed lasalocid prefer lasalocid over monensin when given a choice; however, heifers without previous exposure to an ionophore did not indicate a preference (Exp. 2).     

Chronic lead poisoning in horses

Lead acetate was fed to 4 groups of 2 horses each to study chronic lead intoxication. A 5th group of 3 horses was maintained as controls. The leas was fed in capsules, with the minimum dosage of 6.25 mg/kg/day of lead as lead acetate (group I). The dose was increased from group I through group IV in an approximate geometric series, with each group being given about 125% of the dose given the previous group. These doses were given for 105 days, a period designated as phase 1. Since clinical signs were not observed after 105 days, the doses were increased and fed for an additional 190 days (days 106 to 295). This period was designated phase 2. The smallest daily dose in phase 2 was set at about 125% of the largest daily dose in phase 1. The doses in each group was increased by about 125% of that of the previous group, as was done in phase 1. Seven horses died or were euthanatized after 18 to 190 days of phase 2 (123 to 295 days after the 1st dose). One horse in group I did not develop any clinical signs of intoxication. Dose-related responses were unnoticed with doses larger than 15.3 mg/kg/day. All horses given lead had increased blood lead and serum iron concentrations. During phase 2, the hematocrit (erythrocyte volume) and hemoglobin contents were depressed. The lead concentration in kidney, liver, spleen, pancreas, brain, bone, and heart was increased in the treated horses. The dose level required to produce lead intoxication was greater than that reported for cattle and that estimated in epizootiologic studies of horses.     

Lasalocid toxicity in cattle: acute clinicopathological changes

Thirty-six steers (148 to 500 kg) divided into six equal groups were used in a toxic syndrome study of lasalocid and monensin given as a single oral dose. One group was given a placebo, a second group received monensin (25 mg/kg body weight) and the other four groups received lasalocid at 1, 10, 50 or 100 mg/kg body weight (bw). No toxic signs developed in cattle given placebo or lasalocid at 1 or 10 mg/kg bw dose. The earliest toxic signs were muscle tremors, tachycardia and rumen atony. After 24 h, the cattle were dehydrated, anorectic and had diarrhea. Deaths occurred between d 1 and 22.5 in the groups receiving lasalocid at 50 and 100 mg/kg bw and monensin. Altered values in blood leucocytes, erythrocytes, hemoglobin, hematocrit, total protein, albumin, creatinine, urea nitrogen, total bilirubin, creatine kinase, lactic dehydrogenase, calcium, chloride and inorganic phosphate occurred 1 d after dosing: urine pH and specific gravity also changed 1 d after dosing. Maximum changes occurred at d 3. Most of the changes were indicative of dehydration rather than specific organ damage.     

Oocyst Discharge, Rumen Metabolism and Performance of Early Weaned Lambs with Naturally Occurring Coccidiosis Fed Monensin

Ninety-six 9.5 kg early-weaned lambs with naturally occurring coccidiosis were fed monensin either at 0, 11, 22, or 33 mg/kg of feed for 105 days. Fecal oocyst discharge during the first three days was highest with monensin 22 mg, lowest with monensin 33 mg and averaged 149.6 × 10³ oocysts per gram feces for all lambs. Monensin at 22 mg/kg of feed reduced Eimeria ninakohlyakimovae and E. ahsata oocyst discharge.

Organic matter and crude protein digestibilities were highest (P ≤ 0.05) in lambs fed monensin 22 mg/kg of feed. Monensin increased (P ≤ 0.01) rumen ammonia and propionic acid and decreased (P ≤ 0.01) acetic acid. Feeding monensin 33 mg decreased (P ≤ 0.05) feed intake by 5% and had no effect on gain or feed efficiency. Optimal responses were observed with monensin at 11 mg, feed consumption was not affected, gains were 8% higher (P ≤ 0.05) and feed was utilized 9% more efficiently (P ≤ 0.05) than the controls. In conclusion, monensin was an effective therapeutic agent against naturally occurring coccidial infections in early weaned lambs. Performance responses were largest with monensin fed at the rate of 11 mg/kg of feed.

     

Monensin toxicosis in swine: potentiation by tiamulin administration and ameliorative effect of treatment with selenium and/or vitamin E

Modulation of acute monensin toxicosis in swine was evaluated in 2 studies. In study 1, 56 weanling male pigs were allotted to 14 groups of 4 each. Pigs in 7 groups were given tiamulin in the drinking water (to supply 7.7 mg/kg of body weight/day) for 3 days before and for 2 days after monensin administration. Monensin was given as a single oral dose (at 0, 7.5, 15, 25, 50, 75, or 100 mg/kg) to pigs in groups with or without tiamulin exposure. Prominent acute clinical signs of monensin toxicosis (hypermetria, hind limb ataxia, paresis, knuckling of hind limbs, and recumbency) developed by 2 to 6 hours after dosing in pigs given 15 or 25 mg of monensin/kg with tiamulin exposure, but not in pigs given the 15 or 25 mg of monensin/kg without tiamulin exposure. Also, the extent of monensin-induced skeletal muscle damage at 4 days after monensin dosing was enhanced in pigs given 7.5, 15, or 25 mg of monensin/kg and exposed to tiamulin. In study 2, 48 weanling male pigs were allotted to 8 groups of 6 each. Four groups of pigs were given 20 mg of monensin/kg orally, and 4 groups were given 100 mg of monensin/kg orally. For each monensin dose, a group was treated 24 hours before monensin administration with (i) selenium (Se)-vitamin E preparation, 0.25 mg of Se and 68 IU of d-alpha-tocopheryl acetate (vitamin E)/kg, IM; (ii) vitamin E only, 68 IU of d-alpha-tocopheryl acetate/kg; (iii) Se only, 0.25 mg of Se/kg; or (iv) vehicle.(ABSTRACT TRUNCATED AT 250 WORDS)     

The effect of tiamulin administered by different routes and at different ages to turkeys receiving monensin in their feed

Healthy turkeys receiving 80 ppm monensin in their feed were injected at 26, 40 and 61 days of age with tiamulin at dosages of 12.5 and 25 mg/kg body weight. The aim of the study was to develop a regime for medicating with tiamulin turkeys receiving monensin in their feed, and which would circumvent the known toxicity created by the simultaneous administration of the two drugs. One injection of 12.5 mg/kg tiamulin up to the age of 61 days or 2 injections of 12.5 mg/kg tiamulin up to 40 days of age caused no mortality or adverse reaction.     

Studies on the toxic interaction between monensin and tiamulin in rats: toxicity and pathology

The characteristics of the toxic interaction between monensin and tiamulin were investigated in rats. A three-day comparative oral repeated-dose toxicity study was performed in Phase I, when the effects of monensin and tiamulin were studied separately (monensin 10, 30, and 50 mg/kg or tiamulin 40, 120, and 200 mg/kg body weight, respectively). In Phase II, the two compounds were administered simultaneously to study the toxic interaction (monensin 10 mg/kg and tiamulin 40 mg/kg b.w., respectively). Monensin proved to be toxic to rats at doses of 30 and 50 mg/kg. Tiamulin was well tolerated up to the dose of 200 mg/kg. After combined administration, signs of toxicity were seen (including lethality in females). Monensin caused a dose-dependent cardiotoxic effect and vacuolar degeneration of the skeletal muscles in the animals given 50 mg/kg. Both compounds exerted a toxic effect on the liver in high doses. After simultaneous administration of the two compounds, there was a mild effect on the liver (females only), hydropic degeneration of the myocardium and vacuolar degeneration of the skeletal muscles. The alteration seen in the skeletal muscles was more marked than that seen after the administration of 50 mg/kg monensin alone.     

Comparative toxicology of monensin sodium in laboratory animals

The toxicology of monensin has been studied in several laboratory animal species. There was considerable species variation in acute oral LD50 values. The consistent signs of acute toxicity were: anorexia, hypoactivity, skeletal muscle weakness, ataxia, diarrhea, decreased weight gain and delayed deaths. The 3-mo study in rats fed diets containing 0, 50, 150 or 500 ppm monensin resulted in no effects at the lowest dose level, slight reduction of body weight gain in the middle-dose group and severe depression in body weight gain, skeletal and cardiac lesions, and deaths in the highest dose group. The 3-mo study in dogs given daily oral doses of 0, 5, 15 or 50 mg/kg monensin resulted in no effects at the lowest dose level. Dogs in the 15 and 50 mg/kg groups developed, during test wk 1 to 4, anorexia, weakness, ataxia, labored respiration, body weight loss, increased serum muscle enzyme values, severe skeletal muscle degeneration and necrosis with less severe heart lesions and deaths. Mice fed diets containing 0, 37.5, 75, 150 or 300 ppm monensin for 3 mo had reduced body weight gain in all test groups but no other physical signs. Serum creatine phosphokinase (CPK) values were increased in mice in the two highest dose groups and minimal heart lesions were found in the highest dose group. Dogs given daily oral doses of 0, 1.25, 2.5, 5 or 7.5 mg/kg monensin for 1 yr survived with no evidence of toxicity in the two lowest dose groups.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of long-term administration of an injectable enrofloxacin solution on physical and musculoskeletal variables in adult horses

OBJECTIVE: To evaluate clinical safety of administration of injectable enrofloxacin. DESIGN: Randomized controlled clinical trial. ANIMALS: 24 adult horses. PROCEDURES: Healthy horses were randomly allocated into 4 equal groups that received placebo injections (control) or IV administration of enrofloxacin (5 mg/kg [2.3 mg/lb], 15 mg/kg [6.8 mg/lb], or 25 mg/kg [11.4 mg/lb] of body weight, q 24 h) for 21 days. Joint angles, cross-sectional area of superficial and deep digital flexor and calcaneal tendons, carpal or tarsal osteophytes or lucency, and midcarpal and tarsocrural articular cartilage lesions were measured. Physical and lameness examinations were performed daily. Measurements were repeated after day 21, and articular cartilage and bone biopsy specimens were examined. RESULTS: Enrofloxacin did not induce changes in most variables during administration or for 7 days after administration. One horse (dosage, 15 mg/kg) developed lameness and cellulitis around the tarsal plantar ligament during the last week of administration. One horse (dosage, 15 mg/kg) developed mild superficial digital flexor tendinitis, and 1 horse (dosage, 25 mg/kg) developed tarsal sheath effusion without lameness 3 days after the last administration. High doses of enrofloxacin (15 and 25 mg/kg) administered by bolus injection intermittently induced transient neurologic signs that completely resolved within 10 minutes without long-term effects. Slower injection and dilution of the dose ameliorated the neurologic signs. Adverse reactions were not detected with a 5 mg/kg dose administered IV as a bolus. CONCLUSIONS AND CLINICAL RELEVANCE: Enrofloxacin administered IV once daily at the rate of 5 mg/kg for 3 weeks is safe in adult horses.     

Clinical and epidemiologic features of an epizootic of equine leukoencephalomalacia

A herd of 15 mature riding horses with a history of anorexia, weight loss, and lethargy was examined. The animals had been fed a 50/50 mixture of commercial sweet feed and corn screenings contaminated with a heavy growth of Fusarium moniliforme. Thirteen of the horses had one or more neurologic signs. The most characteristic signs were profound depression and mild ataxia. Over the 19-day course of the epizootic, the horses had increasing severe neurologic deficits, including unilateral blindness and delirium. Despite the clinical appearance of dehydration, 12 horses had low PCV (16 to 27%), hematocrit (21.2 to 31.0%; determined by automated cell counter), and RBC counts (3.76 to 5.5 x 10(6) RBC/microliters). White blood cell counts were variable (4,900 to 17,000 WBC/microliters). Necropsy findings included diffuse malacia of the white matter of the frontal cortex and severe multifocal perivascular hemorrhage in the white matter of the temporal cortex, basal ganglia, anterior medulla, and pons. One horse had a hepatic lesion consisting of a mixed inflammatory cell infiltrate and bile duct proliferation. The attack rate of this epizootic was 100%. The course of disease was unusually long in some animals. In an experiment, the fusarium-infected corn screenings were fed to horses and did not cause clinical signs or alterations in blood or serum biochemical values.     

Serum,milk, and tissue monensin concentrations in cattle with adequate and potentially toxic dietary levels of monensin: pharmacokinetics and diagnostic interpretation

Used in both beef cattle and dairy cows, monensin can provide many health benefits but can, when unintended overexposures occur, result in adverse effects. Information on serum and tissue concentrations following overexposure and/or overt toxicosis which may aid in diagnostics and clinical outcome is lacking. The aim of this study was to determine concentrations of monensin in biological specimens following oral exposure for 10 days to an approved dose (1 mg/kg) and a higher dose (5 mg/kg) of monensin given daily on a body weight basis to 10 dairy cows. No deaths were reported; cows receiving 5 mg/kg showed early signs of toxicosis including depression, decreased feed intake, and diarrhea after 4 days of exposure. Histopathological findings were minimal in most cows. Pharmacokinetic modeling of the detected serum concentrations for the 1 and 5 mg/kg dose groups determined the C_max, T_max, and t_1/2λ to be 0.87 and 1.68 ng/mL, 2.0 and 1.0 h, and 1.76 and 2.32 days, respectively. Mixed regression models showed that the dose level and days since last dose were significantly associated with monensin concentrations in all four tissues, and with cardiac troponin levels. The high dose resulted in a significant elevation of monensin in tissues at approximately 4.7 times compared to the monensin concentrations in the tissues of animals from the low‐dose group. The cTnI concentrations in the high‐dose group were 2.1 times that of cTnI in the low‐dose group. Thus, the ability to diagnose monensin overexposure and/or toxicosis will improve from knowledge of biological monensin concentrations from this study.