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  • Author or Editor: Peter D. Hanson x
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Summary

As more sophisticated research is performed to refine fracture fixation techniques for horses, it is important that normal values for the geometric properties of the bones of the appendicular skeleton be determined and that suitable controls be available. We evaluated the geometric properties of total bone width, cortical bone width, and medullary canal/trabecular bone width measured from 2 radiographic projections of equine long bones (humerus, radius, third metacarpal bone, femur, tibia, and third metatarsal bone) obtained from a general population of horses. Measurements were performed on slices separated by intervals equal to 5% of the bone's length. Slices were then grouped into 5 regions: proximal epiphysis, proximal part of the metaphysis, diaphysis, distal part of the metaphysis, and distal epiphysis. Results validated use of the contralateral bone as a control for assessing experimental models or clinical cases. Of 858 homotypic slice comparisons between left and right bones, significant (P ≤ 0.05) differences were detected in 31 (3.6%) of the comparisons. Of 168 homotypic region comparisons, significant differences were observed in 3 (1.8%) of the comparisons. The greatest variation between left and right bones was observed in metaphyseal regions, areas with bony protuberances, and regions with prominent bone superimposition. At a power of 0.8 for the statistical tests performed in this study, the mean homotypic variation of bones in each region is < 5.8% for the proximal epiphysis, 11.3% for the proximal part of the metaphysis, 6.8% for the diaphysis, 12.2% for the distal part of the metaphysis, and 5.2% for the distal epiphysis.

Free access
in American Journal of Veterinary Research

SUMMARY

We evaluated the single-cycle structural properties for axial compression, torsion, and 4-point bending with a central load applied to the caudal or lateral surface of a diaphyseal segment from the normal adult equine humerus, radius, third metacarpal bone, femur, tibia, and third metatarsal bone. Stiffness values were determined from load-deformation curves for each bone and test mode. Compressive stiffness ranged from a low of 2,690 N/mm for the humerus to a high of 5,670 N/mm for the femur. Torsional stiffness ranged from 558 N · m/rad for the third metacarpal bone to 2,080 N · m/rad for the femur. Nondestructive 4-point bending stiffness ranged from 3,540 N · m/rad for the radius to 11,500 N · m/rad for the third metatarsal bone. For the humerus, radius, and tibia, there was no significant difference in stiffness between having the central load applied to the caudal or lateral surface. For the third metacarpal and metatarsal bones, stiffness was significantly (P < 0.05) greater with the central load applied to the lateral surface than the palmar or plantar surface. For the femur, bones were significantly (P < 0.05) stiffer with the central load applied to the caudal surface than the lateral surface. Four-point bending to failure load-deformation curves had a bilinear pattern in some instances, consisting of a linear region at lower bending moments that corresponded to stiffness values from the nondestructive tests and a second linear region at higher bending moments that had greater stiffness values. Stiffness values from the second linear region ranged from 4,420 N · m/rad for the humerus to 13,000 N · m/rad for the third metatarsal bone. Differences in stiffness between nondestructive tests and the second linear region of destructive tests were significant (P < 0.05) for the radius, third metacarpal bone, and third metatarsal bone. Difference between stiffness values of paired left and right bones was not detected for any test. Four-point bending ultimate failure bending moments ranged from 260 N · m for the femur to 940 N · m for the third metatarsal bone. There was no difference in failure bending moment between the directions of applied central load for a given bone.

Free access
in American Journal of Veterinary Research
in Journal of the American Veterinary Medical Association

Abstract

Objective—To determine cyclooxygenase-2 (COX-2) selectivity, pharmacokinetic properties, and in vivo efficacy of ML-1,785,713 in dogs.

Animals—21 healthy male and female mixed-breed dogs and 24 healthy male Beagles.

Procedure—Selectivity of ML-1,785,713 for inhibiting COX-2 was determined by comparing the potency for inhibiting cyclooxygenase-1 (COX-1) with that of COX-2 in canine blood. Pharmacokinetic properties were determined after IV (2 mg/kg) and oral (8 mg/kg) administration in female mixed-breed dogs. In vivo efficacy was evaluated in male mixed-breed dogs with urate crystal-induced synovitis. Prophylactic efficacy was evaluated by administering ML-1,785,713 two hours before induction of synovitis whereas therapeutic efficacy was determined by administering ML-1,785,713 one hour after induction of synovitis.

Results—Blood concentrations that resulted in 50% inhibition of COX-1 and COX-2 activity in vitro were 119.1µM and 0.31µM, respectively, and selectivity ratio for inhibiting COX-2 relative to COX-1 was 384. ML-1,785,713 had high oral bioavailability (101%), low systemic clearance (7.7 mL/min/kg), and an elimination half-life of 5.9 hours. ML-1,785,713 was efficacious when administered prophylactically and therapeutically to dogs with urate crystal-induced synovitis.

Conclusions and Clinical Relevance—ML-1,785,713 is a novel, potent COX-2 inhibitor that is the most selective COX-2 inhibitor described for use in dogs to date. ML-1,785,713 has oral bioavailability and low systemic clearance that is comparable to other nonsteroidal anti-inflammatory drugs. It is effective after prophylactic and therapeutic administration in attenuating lameness in dogs with urate crystal-induced synovitis. Drugs that specifically inhibit COX-2 and not COX-1 at therapeutic doses may have an improved tolerability profile, compared with nonselective nonsteroidal anti-inflammatory drugs. (Am J Vet Res 2004;65:503–512)

Full access
in American Journal of Veterinary Research

Abstract

Objective—To determine pharmacokinetic parameters and variables, firocoxib concentrations in urine and plasma, urine-to-plasma ratios, and the urine depletion profile of firocoxib and to evaluate whether the pharmacokinetic behavior of firocoxib was governed by linear processes after multiple doses of firocoxib were administered IV and orally.

Animals—6 healthy female horses (5 Paint horses and 1 Quarter Horse) in experiment 1 and 12 healthy male and female horses in experiment 2.

Procedures—In experiment 1, 6 horses were orally administered firocoxib paste once daily for 12 consecutive days, and plasma and urine samples were obtained and analyzed. In a second experiment, 12 horses received IV injections of firocoxib solution once daily for 9 consecutive days, and plasma was obtained and analyzed.

Results—Mean ± SD clearance and steady-state volume of distribution of firocoxib were 40.5 ± 14.7 mL/h/kg and 2.3 ± 0.7 L/kg, respectively. Mean half-life was 44.2 ± 21.6 hours and 36.5 ± 9.5 hours for IV and oral administration, respectively. The urine concentration– time curve decreased in parallel with the plasma concentration-verus-time curve. Renal clearance (0.26 ± 0.09 mL/kg/h) was low, compared with total body clearance, which indicated that the main route of elimination was hepatic clearance.

Conclusions and Clinical Relevance—The pharmacokinetics of firocoxib during prolonged use were determined. Use of plasma or urine to ascertain drug concentrations in horses is scientifically valid because the plasma-to-urine ratio was consistent over time and among horses.

Full access
in American Journal of Veterinary Research

Abstract

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.

Full access
in Journal of the American Veterinary Medical Association