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- Author or Editor: Charles G. MacAllister x
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Abstract
Objective—To assess the analytic sensitivity of an inertial sensor system for detection of the more severely affected forelimb in horses with bilateral lameness.
Animals—18 adult horses with forelimb lameness.
Procedures—Horses were fitted with inertial sensors and evaluated for lameness with a stationary force plate as they were trotted in a straight line. Inertial sensor-derived measurements for vertical head movement asymmetry (HMA) and vector sum (VS) of maximum and minimum head height differences between right and left halves of the stride were used to predict differences in mean peak vertical force (PVF) as a percentage of body weight between the right and left forelimbs. Repeatability was compared by calculation of the intraclass correlation coefficient (ICC) for each variable. Correct classification percentages for the lamer forelimb were determined by use of a stationary force plate as the standard.
Results—SEs of the prediction of difference in PVF between the right and left forelimbs from HMA and VS were 6.1% and 5.2%, respectively. Head movement asymmetry (ICC, 0.72) was less repeatable than PVF (ICC, 0.86) and VS (ICC, 0.84). Associations were positive and significant between HMA (R 2 = 0.73) and VS (R 2 = 0.81) and the difference in PVF between the right and left forelimbs. Correct classification percentages for HMA and VS for detecting the lamer forelimb were 83.3% and 77.8%, respectively.
Conclusions and Clinical Relevance—Results suggested that an inertial sensor system to measure vertical asymmetry (HMA and VS) due to forelimb lameness in horses trotting in a straight line has adequate analytic sensitivity for clinical use. Additional studies are required to assess specificity of the system.
Summary
Thirty young ponies were examined endoscopically for evidence of gastric ulceration. Seven ponies had noninduced gastric ulcers present at the initial examination and were eliminated from the study. In an attempt to induce gastric ulcers experimentally, flunixin meglumine (1.1 mg/kg of body weight, im, q 8 h) was administered for 7 days to the 23 ponies with endoscopically normal gastric mucosa. During the 7 days of flunixin administration, 11 ponies developed gastric ulcers that were appropriate for study. The 11 ponies were randomly allotted to 2 groups. Group-A (n = 5) and group-B (n = 6) ponies received ranitidine (4.4 mg/kg, po, q 8 h) and corn syrup, respectively, until ulcers healed or for a maximum of 40 days. General anesthesia was induced every 3 to 5 days for visual evaluation of ulcer healing by use of a video endoscope. The earliest complete healing of gastric lesions observed in a corn syrup-treated pony was at 17 days. At 40 days, 3 of 5 and 3 of 6 ponies of the ranitidine and corn syrup-treated groups, respectively, had healed ulcers.
Results of this study indicate that: noninduced gastric ulcers may be common in young ponies, flunixin meglumine may be effective in inducing gastric ulcers for gastric healing studies in young ponies, and ranitidine (4.4 mg/kg, q 8 h) is not significantly effective in accelerating healing of experimentally induced gastric ulcers in ponies under conditions of this study.
Abstract
Objective—To determine the pharmacokinetics of acetazolamide administered IV and orally to horses.
Animals—6 clinically normal adult horses.
Procedure—Horses received 2 doses of acetazolamide (4 mg/kg of body weight, IV; 8 mg/kg, PO), and blood samples were collected at regular intervals before and after administration. Samples were assayed for acetazolamide concentration by high-performance liquid chromatography, and concentrationtime data were analyzed.
Results—After IV administration of acetazolamide, data analysis revealed a median mean residence time of 1.71 ± 0.90 hours and median total body clearance of 263 ± 38 ml/kg/h. Median steady-state volume of distribution was 433 ± 218 ml/kg. After oral administration, mean peak plasma concentration was 1.90 ± 1.09 µg/ml. Mean time to peak plasma concentration was 1.61 ± 1.24 hours. Median oral bioavailability was 25 ± 6%.
Conclusions and Clinical Relevance—Oral pharmacokinetic disposition of acetazolamide in horses was characterized by rapid absorption, low bioavailability, and slower elimination than observed initially after IV administration. Pharmacokinetic data generated by this study should facilitate estimation of appropriate dosages for acetazolamide use in horses with hyperkalemic periodic paralysis. (Am J Vet Res 2000;61:965–968)
Abstract
Objective
To determine pharmacokinetics of IV, IM, and oral administration of cefepime in horses and to compare pharmacokinetics of IM administration of cefepime with those of ceftiofur sodium.
Animals
6 clinically normal adult horses.
Procedure
Horses received 3 doses of cefepime (11 mg/kg of body weight, PO; 2.2 mg/kg, IV; and 2.2 mg/kg, IM) and 1 dose of ceftiofur (2.2 mg/kg, IM). Two horses also received l-arginine, PO and IV, at doses identical to those contained in the cefepime dihydrochloride-l-arginine preparations previously administered. Blood samples were collected for 24 hours after administration of cefepime or ceftiofur and were assayed for cefepime and ceftiofur concentrations.
Results
Pharmacokinetic analysis of disposition data indicated that IV administration data were best described by a 2-compartment open model, whereas IM administration data were best described by a 1-compartment absorption model. Median elimination half-life and volume of distribution after IV administration of cefepime were 125.7 minutes and 225 ml/kg, respectively. After IM administration of cefepime, mean maximal plasma concentration of (8.13 μg/ml) was reached at a mean time of 80 minutes. Absorption of cefepime after IM administration was complete, with a median bioavailability of 1.11. Intramuscular administration of ceftiofur resulted in similar mean maximal plasma concentration (7.98 μg/ml) and mean time to this concentration (82 minutes). Cefepime was not detected in samples collected after oral administration. Adverse effects consisting principally of gastrointestinal disturbances were observed after oral and IM administration of cefepime and after 1 IM administration of ceftiofur.
Conclusions and Clinical Relevance
Cefepime, administered IV or IM at a dosage of 2.2 mg/kg, every 8 hours is likely to provide effective antibacterial therapy for cefepime-sensitive organisms in horses. Further studies are needed to evaluate adverse effects on the gastrointestinal tract. (Am J Vet Res 1998;59:458–463)
Summary
Single-dose pharmacokinetic variables of pyrimethamine were studied in horses. Pyrimethamine (1 mg/kg of body weight) was administered iv and orally to 6 adult horses, and plasma samples were obtained at frequent intervals thereafter. Plasma pyrimethamine concentration was assayed by gas chromatography, and concentration-time data were analyzed, using a pharmacokinetic computer program. The iv and oral administration data were best described by 3-compartment and 1-compartment models, respectively. The median volume of distribution at steady state after iv administration was 1,521 ml/kg and the median elimination half-time was 12.06 hours. Mean plasma concentration after oral administration fluctuated between a maximal concentration of 0.18 µg/ml and 0.09 µg/ml (24 hours after dosing). Bioavailability after oral administration was 56%.
Summary
Pharmacokinetics, csf penetration, and hematologic effects of oral administration of pyrimethamine were studied after multiple dosing. Pyrimethamine (1 mg/kg of body weight) was administered orally once a day for 10 days to 5 adult horses, and blood samples were collected frequently after the first, fifth, and tenth doses. The csf samples were obtained by cisternal puncture 4 to 6 hours after administration of the first, third, seventh, and tenth doses. Pyrimethamine concentration in plasma and csf was quantified by gas chromatography, and plasma concentration-time data were analyzed, using a pharmacokinetic computer program. Repeated daily dosing resulted in accumulation of pyrimethamine in plasma, with steady state being achieved within 5 days, when the mean peak plasma concentration was more than twice that measured after the first dose. Pyrimethamine concentration in csf was 25 to 50% of corresponding plasma concentration and did not appear to accumulate with successive administration of doses. Blood samples collected during and after the dosing regimen were submitted for hematologic analysis; neutrophil numbers decreased slightly, but remained within normal range for adult horses.
Abstract
Objective—To evaluate the musculoskeletal analgesic effect of etodolac administered PO every 12 or 24 hours in chronically lame horses by use of force plate analysis.
Animals—22 horses with navicular syndrome.
Procedure—Horses received etodolac (23 mg/kg, PO, q 12 h; n = 7), etodolac (23 mg/kg, PO, q 24 h; 8), or corn syrup (20 mL, PO, q 24 h; control treatment; 7) for 3 days. Combined forelimb peak vertical ground reaction force (PVF) was measured via force plate analysis before the first treatment (baseline) and at 6, 12, 24, and 36 hours after the last treatment. Differences in mean PVF (mPVF) between baseline and subsequent measurements were analyzed (repeated-measures ANOVA) and evaluated for treatment and time effects and treatment-time interaction.
Results—Once- or twice-daily administration of etodolac resulted in significant increases in mPVF from baseline at 6, 12, and 24 hours after the last treatment, compared with the control treatment. There were no significant differences in mPVF between the etodolac treatment groups at any time point. In both etodolac treatment groups, there was a significant increase in mPVF from baseline at 6, 12, and 24 hours, compared with that at 36 hours. Etodolac-associated adverse effects were not detected.
Conclusions and Clinical Relevance—In horses with navicular syndrome, once-daily oral administration of 23 mg of etodolac/kg appears to provide effective analgesia for as long as 24 hours. Twice-daily administration of etodolac at this same dose does not appear to provide any additional analgesic efficacy or duration of effect.
Abstract
Objective—To use force plate analysis to evaluate the analgesic efficacies of flunixin meglumine and phenylbutazone administered IV at typical clinical doses in horses with navicular syndrome.
Animals—12 horses with navicular syndrome that were otherwise clinically normal.
Procedure—Horses received flunixin (1.1 mg/kg), phenylbutazone (4.4 mg/kg), or physiologic saline (0.9% NaCl; 1 mL/45 kg) solution administered IV once daily for 4 days with a 14-day washout period between treatments (3 treatments/horse). Before beginning treatment (baseline) and 6, 12, 24, and 30 hours after the fourth dose of each treatment, horses were evaluated by use of the American Association of Equine Practitioners lameness scoring system (half scores permitted) and peak vertical force of the forelimbs was measured via a force plate.
Results—At 6, 12, and 24 hours after the fourth treatment, subjective lameness evaluations and force plate data indicated significant improvement in lameness from baseline values in horses treated with flunixin or phenylbutazone, compared with control horses; at those time points, the assessed variables in flunixin- or phenylbutazone-treated horses were not significantly different.
Conclusions and Clinical Relevance—In horses with navicular syndrome treated once daily for 4 days, typical clinical doses of flunixin and phenylbutazone resulted in similar significant improvement in lameness at 6, 12, and 24 hours after the final dose, compared with findings in horses treated with saline solution. The effect of flunixin or phenylbutazone was maintained for at least 24 hours. Flunixin meglumine and phenylbutazone appear to have similar analgesic effects in horses with navicular syndrome. (Am J Vet Res 2005;66:284–288)
Summary:
The relative toxicity of phenylbutazone, flunixin meglumine, and ketoprofen was studied in healthy adult horses. Sixteen horses were randomly assigned to receive 10 ml of physiologic saline solution, or ketoprofen (2.2 mg/kg of body weight), flunixin meglumine (1.1 mg/kg), or phenylbutazone (4.4 mg/kg) IV, every 8 hours, for 12 days. Results of CBC, serum biochemical analyses, and fecal occult blood tests were monitored. On day 13, all horses were euthanatized and complete necropsy examinations were performed.
Mean CBC values remained within normal limits for all groups. Phenylbutazone-treated horses had a significant (P < 0.05) decrease in serum total protein and albumin concentrations. Mean values of all other serum biochemical assays were not different from those of the saline-treated group. Results of all fecal occult blood tests were negative. At necropsy, the glandular portion of the stomach was the area of the gastrointestinal tract most severely affected by phenylbutazone, flunixin meglumine, and ketoprofen. In the phenylbutazone-treated group, but not in the other groups, edema of the small intestine and erosions and ulcers of the large colon were observed. None of the horses treated with saline solution had lesions in the glandular portion of the stomach or in the intestine. Four horses (1/5 and 3/3 in the flunixin- and phenylbutazone-treated groups, respectively) developed renal crest necrosis. Horses in the saline- and ketoprofen-treated groups did not develop renal lesions. Under the conditions of this study and with total daily doses that exceeded the manufacturers' recommended doses, the toxic potential of the 3 nonsteroidal anti-inflammatory drugs was greatest for phenylbutazone, less for flunixin meglumine, and least for ketoprofen in clinically normal adult horses.
Summary:
The effect of sucralfate on healing of subclinical gastric ulcers and gastric inflammation was investigated in twelve 6- to 7-month-old foals. Foals with endoscopically evident gastric lesions on day 0 were assigned to 1 of 2 groups, on the basis of mucosal inflammation and number and severity of ulcers, to create groups of foals with approximately equal severity of lesions. None of these foals had clinical signs of gastroduodenal ulcer disease. Groups were assigned to receive sucralfate (22.0 mg/kg of body weight) or corn syrup for 14 days, po, every 8 hours. On day 15, gastroscopic examinations revealed that sucralfate did not promote greater healing than did the corn syrup.