Efficacy of an oxibendazole-trichlorfon paste formulation against third stage larvae of Gasterophilus intestinalis and its safety in horses

A paste formulation containing 14.3 per cent of oxibendazole and 44 per cent of trichlorfon was administered to 33 ponies and horses. The dose rate used was equivalent to 10 mg and 30 mg/kg bodyweight, of oxibendazole and trichlorfon respectively. After treatment 25 animals passed between one and 82 third stage larvae of Gasterophilus intestinalis in their faeces. Dosing with 0.2 mg ivermectin/kg bodyweight three weeks later resulted in six animals expelling between one and four bots. The efficacy of the oxibendazole-trichlorfon paste was on average 96.2 per cent. This drug combination given to 52 ponies and horses at the indicated dose rate and to six ponies at twice that dose was tolerated without side effects except transient softening of the faeces in several animals and mild symptoms of colic in two horses.     

Critical tests and safety studies on trichlorfon as an antiparasitic agent in the horse.

Three series of critical tests were completed on a combined total of 46 horses to determine the efficacy of single doses of trichlorfon against bots, ascarids, pinworms, and large strongyles. Different formulations of trichlorfon were administered by tubing intragastrically, mixing with the daily grain ration, injecting intramuscularly, or pouring on the back at dose rates between 20 and 100 mg/kg. Administration by feeding tended to be more efficacious for removal of bots and less toxic to the horese than administration by stomach tube. In many of the tests, trichlorfon was given in the grain ration at the dose rate of 40 mg/kg of body weight, and the aggregate average removals of 2nd and 3rd instars of Gastrophilus intestinalis and Gasterophilus nasalis in the 3 series of tests were between 97 and 100%. Removal of Parascaris equorum was equally efficacious with both the intubation and the grain feeding methods of dosing, and at the dose rate of 40 mg/kg, the aggregate averages were 99 and 100% in the 3 series. Removal of Oxyuris equi was variable--aggregate averages were between 11 (1 infected horse in the initial series) and 96 (5 infected horses in the 3rd series) to 100% (7 infected horses in the 2nd series). Large strongyles, Strongylus vulgaris and Strongylus edentatus were almost completely refractory to the 40-mg/kg dose rate of trichlorfon. Dose rates of 40 mg/kg and less were generally well tolerated by the critical test horses. Higher dose rates (60 and 80 mg/kg) administered by stomach tube induced moderately severe to severe colic and diarrhea, whereas a dose of 80 mg/kg given in the feed resulted in only a transient softening of the feces. Likewise, 5 consecutive doses, 1 week between doses, of a bolus formulation given at the rate of 80 mg/kg to 4 horses were well tolerated. Clinical trials involving a total of 2,294 treatments of trichlorfon at dose rate of 35 to 40 mg/kg in pregnant and nonpregnant mares, stallions, suckling and weanling foals, yearlings, and horses in training on 38 farms in central Kentucky did not cause notable adverse clinical effects.     

Critical tests of morantel-trichlorfon paste formulation against internal parasites of the horse

Critical tests were completed on six horses to evaluate the antiparasitic activity of a paste formulation mixture of morantel citrate and trichlorfon, administered intraorally at the dose rate of 6 mg morantel base kg-1 and trichlorfon at 30 mg kg-1. Aggregate average removals were: 78% for two horses infected with 2nd instar Gasterophilus intestinalis; 100% for one infected with 2nd instar G. nasalis; 96% for six infected with 3rd instar G. intestinalis; 100% for four infected with 3rd instar G. nasalis; 100% for five infected with Parascaris equorum; 100% for one infected with mature Oxyuris equi; 100% for five infected with Strongylus vulgaris; 72% for five infected with S. edentatus; and partial removal (25%) of Anoplocephala perfoliata infection from one infected animal. Pre- and post-treatment EPG and LPG data indicated a reduction of 97% of the mature small strongyle infections. Evidence of toxicosis was not observed in any of the horses.     

Prevalence and Treatment of Tapeworms in Horses

A study was initiated to determine the prevalence of tapeworms in horses in Southern Ontario and to investigate the efficacy of pyrantel pamoate, niclosamide and mebendazole. Fecal samples were taken from 580 horses of various breeds, ages and sexes in 24 locations and Anoplocephala perfoliata was found in 13.6%. This was regarded as a minimum, the true rate being probably significantly higher and the reasons for this are discussed. A brief review of the life cycle and effects of tapeworms in horses and a comparison of two flotation techniques for the diagnosis of A. perfoliata eggs in feces is given.Pyrantel pamoate, niclosamide and mebendazole were compared for efficacy in field and critical trials. In field trials, pyrantel base and niclosamide at 6.6 and 50 mg/kg respectively were found to be effective, but in critical trials their efficacy was poor, 15 and 5.6% respectively. These anthelmintics at these dose rates caused only an elimination of the terminal egg bearing segments and were without significant effect on the entire tapeworm. When pyrantel base was administered at 13.2 and 19.8 mg/kg (twice and three times the therapeutic dose rate for nematodes respectively) the efficacy was 97.8 and 100%. It would appear that pyrantel pamoate administered at 13.2 mg pyrantel base/kg is an effective therapeutic dose for tapeworms in horses. Further dose titration studies are needed for niclosamide. Mebendazole was without effect at up to four (35.2 mg/kg) times the therapeutic dose for nematodes.     

Comparison of paste and suspension formulations of omeprazole in the healing of gastric ulcers in racehorses in active training

OBJECTIVE: To compare effects of a commercially available omeprazole paste and a compounded omeprazole suspension on healing of gastric ulcers in Thoroughbred racehorses in active training. DESIGN: Randomized controlled trial. ANIMALS: 32 horses with gastric ulcers. PROCEDURE: Horses were assigned to 2 groups on the basis of endoscopic gastric ulcer severity. Group-1 horses were treated with omeprazole suspension for 30 days and with omeprazole paste for an additional 30 days. Group-2 horses were treated with omeprazole paste for 30 days and omeprazole suspension for an additional 30 days. Serum omeprazole concentrations were measured in 4 additional healthy horses after administration of a single dose of each formulation. In all instances, omeprazole was administered at a dose of 4 mg/kg (1.8 mg/lb), p.o.. RESULTS: Ulcer severity scores on day 0 were not significantly different between groups. On day 30, ulcer severity score was significantly decreased, compared with day-0 score, in group-2 but not in group-1 horses. On day 60, ulcer severity score was significantly decreased, compared with day-0 and day-30 scores, in group-1 horses. In group-2 horses, ulcer severity score on day 60 was significantly lower than the day-0 score but was not significantly different from the day-30 score. Maximum observed serum omeprazole concentration and area under the concentration-time curve were significantly higher after administration of the paste versus the suspension formulation. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that although administration of the commercially available paste omeprazole formulation was effective in promoting healing of gastric ulcers in these horses, administration of the compounded omeprazole suspension was ineffective.     

The persistence of benzimidazole-resistant cyathostomes on horse farms in Ontario over 10 years and the effectiveness of ivermectin and moxidectin against these resistant strains

Three clinical trials with fecal egg count reduction tests and coproculture were conducted on 2 standardbred farms in Ontario. On Farm A, the treatment groups were mebendazole and ivermectin in trial 1, and fenbendazole and moxidectin in another. On Farm B, treatment groups were mebendazole and ivermectin. All horses treated with mebendazole or fenbendazole were subsequently treated with ivermectin or moxidectin. Strongyle eggs/g feces were estimated pre- and post-treatment using the Cornell-McMaster dilution and Cornell-Wisconsin centrifugal flotation techniques. After treatment, there was no change in the arithmetic mean eggs/g feces for horses given mebendazole, and a reduction of only 49.1% for those given fenbendazole. All horses receiving ivermectin or moxidectin had their egg counts reduced to 0. Only cyathostomes were found on culture. On both farms the benzimidazole resistant strains appeared to have persisted for at least 10 years. Development of and monitoring for anthelmintic resistance are briefly discussed.     

Target animal safety and tolerance study of pyrantel pamoate paste (19.13% w/w pyrantel base) administered orally to horses

Pyrantel pamoate paste (19.13% w/w pyrantel base) for the treatment of tapeworm, Anoplocephala spp was evaluated for target animal safety and tolerance in horses treated orally at 0, 1, 3, 5, and 10 times the clinical dose of 13.2 mg pyrantel base/kg body weight administered daily for six consecutive days. Parameters evaluated included clinical signs, food and water consumption, body weights, physical examinations, clinical pathology (hematology, coagulation, serum chemistry, urinalyses, and fecal examinations), complete necropsy, organ weights, and histopathology. No adverse events or test article-related effects were observed in any treatment group during daily clinical observations of the test animals. Statistically significant changes (P < .05) lacked a dose- and/or time-dependent trend and were considered incidental. Administration of pyrantel pamoate paste did not produce any macroscopic or microscopic tissue effects in any dose group of either sex. The no-observed-effect-level (NOEL) for pyrantel pamoate paste, when administered orally to horses once daily for 6 consecutive days, was determined to be 132 mg/kg/day. Pyrantel pamoate paste (19.13% w/w pyrantel base) can be safely administered orally to horses at 13.2 mg of pyrantel base/kg for the treatment of Anoplocephala infestations.     

Efficacy of mebendazole against Dictyocaulus arnfieldi in the donkey.

In a controlled trial in naturally infected donkeys the efficacy of mebendazole against Dictyocaulus arnfieldi infection was evaluated. A powder formulation of mebendazole given orally at a dosage rate of 4.3 to 5.7 mg per kg per day for five days had no apparent effect on existing lungworm burdens. However a paste formulation of mebendazole given orally at a higher dosage rate of 15.2 to 20.0 mg per kg per day for five days was 75 to 100 per cent effective in the removal of lungworms from individual animals.     

Effectiveness of administration of phenylbutazone alone or concurrent administration of phenylbutazone and flunixin meglumine to alleviate lameness in horses

OBJECTIVE: To determine the effectiveness of administering multiple doses of phenylbutazone alone or a combination of phenylbutazone and flunixin meglumine to alleviate lameness in horses. ANIMALS: 29 adult horses with naturally occurring forelimb and hind limb lameness. PROCEDURES: Lameness evaluations were performed by use of kinematic evaluation while horses were trotting on a treadmill. Lameness evaluations were performed before and 12 hours after administration of 2 nonsteroidal anti-inflammatory drug (NSAID) treatment regimens. Phenylbutazone paste was administered at approximately 2.2 mg/kg, PO, every 12 hours for 5 days, or phenylbutazone paste was administered at approximately 2.2 mg/kg, PO, every 12 hours for 5 days in combination with flunixin meglumine administered at 1.1 mg/kg, IV, every 12 hours for 5 days. RESULTS: Alleviation of lameness was greater after administration of the combination of NSAIDs than after oral administration of phenylbutazone alone. Improvement in horses after a combination of NSAIDs did not completely mask lameness. Five horses did not improve after either NSAID treatment regimen. All posttreatment plasma concentrations of NSAIDs were less than those currently allowed by the United States Equestrian Federation Inc for a single NSAID. One horse administered the combination NSAID regimen died of acute necrotizing colitis during the study. CONCLUSIONS AND CLINICAL RELEVANCE: Administration of a combination of NSAIDs at the dosages and intervals used in the study reported here alleviated the lameness condition more effectively than did oral administration of phenylbutazone alone. This may attract use of combinations of NSAIDs to increase performance despite potential toxic adverse effects.     

Effect of drug formulation and feeding on the pharmacokinetics of orally administered quinidine in the horse

Quinidine is the drug of choice for the treatment of cardiac arrhythmias in horses. The plasma concentrations vs. time profiles following oral administration of two formulations of quinidine sulphate, an oral solution and an oral suspension paste, were evaluated in nine horses. They received multiple administrations of the oral solution under fed and non-fed conditions and of the paste under non-fed conditions. A loading dose of 20 mg.kg_-1 and a maintenance dose of 10 mg.kg^-1 quinidine with dosing interval of 6 h were used. The relative bioavailability of the oral solution under fed conditions in comparison to the solution under non-fed conditions was 75.0 ± 10.2% for the loading dose and 97.18 ± 31.66% after the fourth dose. For the paste formulation the relative bioavailability values are not reported, as steady-state levels were not reached. There was a large variation in plasma quinidine levels when the paste formulation was administered. Feeding conditions had a significant influence on the C_max, values after administration of the loading dose. The T ^max values were not affected by food intake. It was concluded that an oral solution has to be preferred because of the variable drug bioavailability from the paste formulation and the poor acceptability of the paste by the horse.     

Physiological, biochemical and haematological effects on horses of a phenylbutazone paste

Five matched pairs of horses were used to investigate the biochemical, haematological and general clinical effects of a new dosage schedule of a phenylbutazone paste administered under controlled feeding conditions. One group of horses received a loading dose (8.8 mg/kg) on day 1, followed by doses of 3.3 mg/kg daily on days 2 to 8, 10 and 12 with no treatment on days 9 and 11. The second group received equivalent doses of a placebo paste. Bodyweight, skin temperature, respiratory rate, glutamate dehydrogenase activity, packed cell volume, mean corpuscular volume and neutrophil count were altered significantly in the drug-treated but not in the placebo-treated animals. From the direction and magnitude of the changes in these variables, it was concluded that they did not reflect toxic actions of phenylbutazone. Several variables were unaffected by either treatment both during and after dosing and others were significantly altered in both groups of horses. These changes were considered to be toxicologically insignificant.     

Influence of formulation on the pharmacokinetics and bioavailability of racemic ketoprofen in horses

The bioavailability of S(+) and R(-) ketoprofen (KTP) in six horses was investigated after oral administration of the racemic (rac) mixture. Two oral formulations were studied, an oil-based paste containing micronised rac-KTP and powder from the same source in hard gelatin capsules, each at a dose rate of 2.2 mg/kg. For the oil-based paste two feeding schedules were used; horses were either allowed free access to food or access to food was restricted for 4 h before and 5 h after dosing. The drug in hard gelatin capsules was administered to horses with restricted access to food. After intravenous administration of rac-KTP, S(+) enantiomer concentrations exceeded those of the R(-) enantiomer. For S(+) and R(-)KTP. respectively, pharmacokinetic parameters were, t_1/2β 0.99 ± 0.14 h, 0.70 ±0.13 h;C/_B 0.56±0.09,0.92±0.20 L/h/kg; V_d(ss), 0.53 ±0.11.0, 61±0.10L/kg. Following oral administration of rac-KTP as the oil-based paste to horses with free access to food, there were no detectable concentrations in plasma in three animals at any sampling time, while a fourth animal showed very low concentrations at two sampling times only. In the two remaining horses very low but detectable concentrations were present for 5 h. In the horses with restricted access to food, rac-KTP paste administration produced higher concentrations in plasma. However, bioavailability was very low, 2.67 ± 0.43 and 5.75 ± 1.48% for R(-) and S(+)KTP, respectively. When administered as pure drug substance in hard gelatin capsules, absorption of KTP was fairly rapid, but incomplete. Bioavailability was 50.55 ± 10.95 and 54.17 ±9.9% for R(-) and S(+)KTP, respectively. This study demonstrates that rac-KTP had a modest bioavailability when administered as a micronised powder in hard gelatin capsules to horses with restricted access to food. When powder from the same source was administered as an oil-based paste, it was for practical purposes not bioavailable, regardless of the feeding schedule.     

Verification of ineffectual activity of ivermectin against adult Onchocerca spp in the ligamentum nuchae of horses

Ivermectin paste formulation (200 micrograms/kg) was administered orally to 27 horses (13 Thoroughbreds and 14 of mixed breeding) to evaluate activity against adult Onchocerca spp in the ligamentum nuchae. Ages, known or estimated, of the horses ranged from 1 to 22 years. Single or multiple doses (1 to 5) of the drug were given to each horse. When multiple doses were administered, the intervals between treatments ranged from 7 to 92 days. At 27 to 171 days after initial treatment (single dose or first of multiple doses), the horses were killed. Some of the horses treated more than once were killed as soon as 7 days after the last treatment. At necropsy, Onchocerca spp were found in the ligamentum nuchae of 24 (89%) of the 27 horses. All of the specimens were pieces of worms, apparently adult, which appeared to be alive. The only noninfected horses were 2 to 3 years old. In 18 (75%) of the 24 infected horses, microfilariae, most being obviously viable, were found in the worm specimens or ligamentum nuchae.     

Critical tests and clinical trials on oxibendazole in horses with special reference to removal of Parascaris equorum.

The efficacy of oxibendazole given at dose level of 10 mg/kg of body weight was determined by 10 critical tests in foals and by 2 clinical trials in 20 foals (16 treated, 4 nontreated), with special interest in the drug activity against Parascaris equorum. The drug was uniformly efficacious (100%) against P equorum in the 10 critical-test foals, each having between 22 and 236 ascarids. Posttreatment reductions of ascarid egg counts in fecal samples were also 100% in suckling foals treated with oxibendazole given as a drench. Ascarid eggs did not reappear in fecal samples until the 8th week after foals were treated. A paste formulation of oxibendazole at 10 mg/kg also eliminated ascarid eggs from feces of 12 suckling foals. Strongyle EPG were markedly reduced by oxibendazole in the 10 critical-test foals and in 16 treated sucklings in the clinical trials. Egg and larval count data on foals in both the critical tests and the clinical trials also indicated oxibendazole was active against Strongyloides westeri. Untoward effects of treatment with oxibendazole were not observed.     

Benzimidazole resistance of equine strongyles: critical tests of several classes of compounds against population B strongyles from 1977 to 1981

From 1977 to 1981, critical tests were conducted on 10 horses naturally infected with population B strongyles. Drugs tested were: oxibendazole (OBZ), 10 mg/kg of body weight (n = 1); albendazole, 10 mg/kg (n = 1); a mixture of thiabendazole (TBZ), 44 mg/kg and trichlorfon, 40 mg/kg (n = 1); a mixture of TBZ at 44 mg/kg with piperazine (PPZ) at 55 mg of base/kg (n = 1); febantel (FBT), 6 mg/kg (n = 3), 12 mg/kg (n = 1), or 24 mg/kg (n = 1); and pyrantel (PRT) pamoate, 6.6 mg of base/kg (n = 1). Large strongyles, Strongylus vulgaris (9 horses) and S edentatus (5 horses), were effectively removed (100%) by each compound and mixture. Five species of small strongyles (Cyathostomum catinatum, Cyathostomum coronatum, Cylicocyclus nassatus, Cylicostephanus goldi, and Cylicostephanus longibursatus), previously singled out in this population as resistant to 5 benzimidazoles (TBZ, mebendazole, cambendazole, fenbendazole, and oxfendazole), but not OBZ, were efficaciously removed by OBZ, albendazole, the mixture of TBZ plus PPZ, FBT (24 mg/kg), or PRT. These 5 small strongyle species were resistant to FBT (6 mg/kg) in 3 foals and Cylicostephanus minutus was also resistant in 2 of 3 foals to FBT (6 mg/kg). Doubling the dose of FBT to 12 mg/kg increased the average removal of the 5 basic species plus Cylicostephanus minutus to 88%. The mixture of TBZ and trichlorfon was relatively ineffective against 3 species (C catinatum, C coronatum, and Cylicostephanus longibursatus), but unexpectedly efficacious (86% to 99%) for 2 species (Cylicocyclus nassatus and Cylicostephanus goldi).(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of intravenously administrated omeprazole on gastric juice pH and gastric ulcer scores in adult horses

The study was performed to evaluate the efficacy of omeprazole powder in sterile water, administered intravenously, on gastric juice pH in adult horses with naturally occurring gastric ulcers. Omeprazole (0.5 mg/kg, IV) was administered once daily for 5 days to 6 adult horses with gastric ulcers. Gastric juice was aspirated through the biopsy channel of an endoscope and pH was measured before and 1 hour after administration of omeprazole on day 1, and then before and after administration of omeprazole on day 5. Gastric ulcer scores were recorded on day 1 before administration of omeprazole and on day 5, 23 hours after the 4th daily dose. Gastric juice pH and ulcer scores were compared between the times. When compared with the pre-injection value (2.01 +/- 0.42), mean +/- SD gastric juice pH was significantly higher when measured 1 hour after administration of the initial dose (4.35 +/- 2.31), and before (5.27 +/- 1.74) and 1 hour after (7.00 +/- 0.25) administration of omeprazole on day 5. Nonglandular gastric ulcer number score significantly decreased from a mean +/- SD of 3.2 +/- 0.80 to 2.0 +/- 1.1, but nonglandular gastric ulcer severity score remained the same. Few glandular ulcers were seen in the study, and scores did not change. Because of its potent and long duration of action on gastric juice pH, this intravenous formulation of omeprazole may show promise for treatment of equine gastric ulcer syndrome (EGUS) in horses with dysphagia, gastric reflux, or other conditions that restrict oral intake of omeprazole paste. Aspiration of gastric juice and measurement of pH can be of use to determine whether the desired pH > 4.0 has been reached after omeprazole treatment.     

Pharmacokinetics and pharmacodynamics of three formulations of firocoxib in healthy horses

The objectives of this study were to compare the pharmacokinetics and COX selectivity of three commercially available formulations of firocoxib in the horse. Six healthy adult horses were administered a single dose of 57 mg intravenous, oral paste or oral tablet firocoxib in a three‐way, randomized, crossover design. Blood was collected at predetermined times for PGE₂ and TXB₂ concentrations, as well as plasma drug concentrations. Similar to other reports, firocoxib exhibited a long elimination half‐life (31.07 ± 10.64 h), a large volume of distribution (1.81 ± 0.59L/kg), and a slow clearance (42.61 ± 11.28 mL/h/kg). Comparison of the oral formulations revealed a higher C_max, shorter T_max, and greater AUC for the paste compared to the tablet. Bioavailability was 112% and 88% for the paste and tablet, respectively. Maximum inhibition of PGE₂ was 83.76% for the I.V. formulation, 52.95% for the oral paste formulation, and 46.22% for the oral tablet formulation. Pharmacodynamic modeling suggests an IC₅₀ of approximately 27 ng/mL and an IC₈₀ of 108 ng/ mL for COX2 inhibition. Inhibition of TXB₂ production was not detected. This study indicates a lack of bioequivalence between the oral formulations of firocoxib when administered as a single dose to healthy horses.     

Effects of phenylbutazone alone or in combination with flunixin meglumine on blood protein concentrations in horses

OBJECTIVE: To assess effects of treatment with phenylbutazone (PBZ) or a combination of PBZ and flunixin meglumine in horses. ANIMALS: 24 adult horses. PROCEDURE: 13 horses received nonsteroidal antiinflammatory drugs (NSAIDs) in a crossover design. Eleven control horses were exposed to similar environmental conditions. Treated horses received PBZ (2.2 mg/kg, PO, q 12 h, for 5 days) and a combination of PBZ and flunixin meglumine (PBZ, 2.2 mg/kg, PO, q 12 h, for 5 days; flunixin meglumine, 1.1 mg/kg, IV, q 12 h, for 5 days). Serum samples were obtained on day 0 (first day of treatment) and day 5, and total protein, albumin, and globulin were measured. RESULTS: 1 horse was euthanatized with severe hypoproteinemia, hypoalbuminemia, and colitis during the combination treatment. Comparisons revealed no significant difference between control horses and horses treated with PBZ alone. There was a significant difference between control and treated horses when administered a combination of PBZ and flunixin meglumine. Correction for horses with values >2 SDs from the mean revealed a significant difference between control horses and horses administered the combination treatment, between control horses and horses administered PBZ alone, and between horses receiving the combination treatment and PBZ alone. Gastroscopy of 4 horses revealed substantial gastric ulcers when receiving the combination NSAID treatment. CONCLUSIONS AND CLINICAL RELEVANCE: Analysis of results of the study indicates the need for caution when administering a combination NSAID treatment to horses because the detrimental effects may outweigh any potential benefits.     

Comparison of efficacy and safety of paste formulations of firocoxib and phenylbutazone in horses with naturally occurring osteoarthritis

OBJECTIVE: To compare efficacy and safety of paste formulations of firocoxib and phenylbutazone in horses with naturally occurring osteoarthritis. DESIGN: Randomized controlled clinical trial. ANIMALS: 253 client-owned horses with naturally occurring osteoarthritis. PROCEDURES: Horses were treated with firocoxib (0.1 mg/kg [0.045 mg/lb], PO, q 24 h) or phenylbutazone (4.4 mg/kg [2 mg/lb], PO, q 24 h) for 14 days. Physical examinations and lameness evaluations were performed prior to treatment and after 7 and 14 days. Clinical improvement was defined as a reduction of at least 1 lameness grade or a combined reduction of at least 3 points in scores for pain during manipulation or palpation, joint swelling, joint circumference, and range of motion. RESULTS: Proportion of horses clinically improved on day 14 for the firocoxib group (104/123 [84.6%]) was not significantly different from the proportion for the phenylbutazone group (103/119 [86.6%]). Proportion of horses that were improved on day 14 was significantly greater for horses treated with firocoxib than for horses treated with phenylbutazone with regard to score for pain on manipulation or palpation (P = 0.028), joint circumference score (P = 0.026), and range of motion score (P = 0.012), but not for overall lameness score or joint swelling score. No direct treatment-related adverse effects were detected during the study. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested that overall clinical efficacy of a paste formulation of firocoxib in horses with naturally occurring osteoarthritis was comparable to efficacy of a paste formulation of phenylbutazone.     

Pharmacokinetics and clinical effects of a subanesthetic continuous rate infusion of ketamine in awake horses

OBJECTIVE: To determine the pharmacokinetics and clinical effects of a subanesthetic, continuous rate infusion of ketamine administered to healthy awake horses. ANIMALS: 8 adult horses. PROCEDURES: Ketamine hydrochloride was administered to 2 horses, in a pilot study, at rates ranging from 0.4 to 1.6 mg/kg/h for 6 hours to determine an appropriate dose that did not cause adverse effects. Ketamine was then administered to 6 horses for a total of 12 hours (3 horses at 0.4 mg/kg/h for 6 hours followed by 0.8 mg/kg/h for 6 hours and 3 horses at 0.8 mg/kg/h for 6 hours followed by 0.4 mg/kg/h for 6 hours). Concentration of ketamine in plasma, heart rate, respiratory rate, blood pressure, physical activity, and analgesia were measured prior to, during, and following infusion. Analgesic testing was performed with a modified hoof tester applied at a measured force to the withers and radius. RESULTS: No signs of excitement and no significant changes in the measured physiologic variables during infusion rates of 0.4 and 0.8 mg of ketamine/kg/h were found. At 6 hours following infusions, heart rate and mean arterial pressure were decreased, compared with preinfusion measurements. An analgesic effect could not be demonstrated during or after infusion. Pharmacokinetic variables for 0.4 and 0.8 mg/kg/h infusions were not significantly different. CONCLUSIONS AND CLINICAL RELEVANCE: Ketamine can be administered to awake horses at 0.4 or 0.8 mg/kg/h without adverse behavioral effects. The observed pharmacokinetic values are different than those reported for single-dose IV bolus administration of this drug.