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Abstract

OBJECTIVE

To characterize the pharmacokinetics of mycophenolate mofetil (MMF) following single-dose IV or PO administration, characterize the pharmacokinetics of MMF following long-term PO administration, and describe the clinicopathologic effects of long-term MMF administration in horses.

ANIMALS

12 healthy adult horses.

PROCEDURES

In phase 1, 6 horses received a single IV (2.5 mg/kg) or PO (5 mg/kg) dose of MMF in a randomized balanced crossover assessment (≥ 2-week interval between administrations). In phase 2, 6 other horses received MMF for 60 days (5 mg/kg, PO, q 24 h for 30 days and then 5 mg/kg, PO, q 48 h for an additional 30 days).

RESULTS

Following IV (single-dose) or PO (single- or multiple-dose) administration, MMF was rapidly converted to mycophenolic acid. For single-dose PO administration, mean ± SD maximum plasma mycophenolic acid concentration was 1,778.3 ± 441.5 ng/mL at 0.71 ± 0.29 hours. For single-dose IV administration, mean systemic clearance and volume of distribution at steady state were 0.689 ± 0.194 L/h/kg and 1.57 ± 0.626 L/kg, respectively. Following single doses, mean terminal half-life was 3.99 ± 0.865 hours for IV administration and 4.02 ± 1.01 hours for PO administration. The accumulation index following long-term PO administration was 1.0 ± 0.002, and the terminal half-life was 4.59 ± 1.25 hours following the final dose on day 60. None of the horses developed abnormal clinical signs or had any consistently abnormal clinicopathologic findings.

CONCLUSIONS AND CLINICAL RELEVANCE

Further investigation of the clinical efficacy of long-term MMF treatment of horses with autoimmune diseases is warranted.

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in American Journal of Veterinary Research

Abstract

Objective—To assess heritability and mode of inheritance for hereditary equine regional dermal asthenia (HERDA) in Quarter Horses.

Animals—1,295 horses with Quarter Horse bloodlines, including 58 horses affected with HERDA.

Procedure—Horses were classified as affected or unaffected or as undetermined when data were insufficient to assess phenotype. Pedigree data were analyzed to determine the probable mode of inheritance. Heritability was estimated by use of Bayesian statistical methods.

Results—Heritability (mean ± SD) of HERDA was estimated to be 0.38 ± 0.13, with both sexes having an equal probability of being affected. Results for evaluation of the pedigrees were consistent with a single Mendelian autosomal recessive mode of inheritance.

Conclusions and Clinical Relevance—HERDA in Quarter Horses is an inherited disease, and affected horses are more likely to produce affected offspring. An autosomal recessive mode of inheritance should be considered by people making breeding decisions involving Quarter Horses when a first-degree relative has been confirmed with HERDA or has produced affected offspring. In addition, breeders whose horses have produced affected offspring can reduce the likelihood of producing affected horses in the future by avoiding inbreeding. (Am J Vet Res 2005;66:437–442)

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in American Journal of Veterinary Research
History

A 10-month-old 28.6-kg (62.9-lb) sexually intact female chocolate Labrador Retriever was referred to the veterinary dermatology service at a veterinary medical teaching hospital for evaluation because of a 2-month history of progressive crusting dermatitis with associated pruritus. The owners described the crusting lesions as resembling tree bark. Skin lesions were progressive, and treatment of the dog for 6 weeks with an elimination diet trial, an ectoparasite control product, and systemic and topical antimicrobial administration was ineffective. Results of examination of skin scraping preparations, fecal flotation testing, and screening for heartworm and tick-borne diseases were negative. Bacterial culture and antimicrobial

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in Journal of the American Veterinary Medical Association

Abstract

Objective—To evaluate a method of aerobic bacteriologic culture of epidermal collarette specimens from dogs with superficial pyoderma and compare results with those for aerobic bacteriologic culture of abdominal skin specimens in healthy dogs.

Design—Prospective study.

Animals—22 dogs with epidermal collarettes and 24 healthy dogs.

Procedure–Dry sterile cotton swabs were rolled across epidermal collarettes or hairless areas of abdominal skin in healthy dogs and submitted for aerobic bacteriologic culture. Hemolytic colonies of gram-positive–staining cocci were tested for catalase production, and if results were positive, a coagulase test was performed. Colonies with coagulase activity were tested for the ability to ferment mannitol. Antimicrobial susceptibility testing was performed on all Staphylococcus spp that were isolated.

ResultsS intermedius was isolated from collarettes in 18 of 22 dogs with superficial pyoderma but not from healthy dogs. Estimated sensitivity and specificity of the culture method were 81.8% and 100%, respectively. There were no significant differences in the ability to culture S intermedius, the number of S intermedius isolates without resistance to antimicrobials, and the number of S intermedius isolates resistant to penicillin G when comparing dogs with superficial pyoderma for the first time and dogs with recurrent pyoderma, dogs that did or did not receive concurrent antimicrobials, and dogs with and without underlying allergic disease.

Conclusions and Clinical Relevance–Bacteriologic culture of epidermal collarette specimens was a simple and reliable method for identification of S intermedius in dogs with superficial pyoderma, regardless of history of pyoderma or current antimicrobial use. (J Am Vet Med Assoc 2005;226:904–908)

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in Journal of the American Veterinary Medical Association

Abstract

Objective—To determine pharmacokinetics of azathioprine (AZA) and clinical, hematologic, and serologic effects of IV and oral administration of AZA in horses.

Animals—6 horses.

Procedure—In study phase 1, a single dose of AZA was administered IV (1.5 mg/kg) or orally (3.0 mg/kg) to 6 horses, with at least 1 week between treatments. Blood samples were collected for AZA and 6-mercaptopurine (6-MP) analysis 1 hour before and at predetermined time points up to 4 hours after AZA administration. In study phase 2, AZA was administered orally (3 mg/kg) every 24 hours for 30 days and then every 48 hours for 30 days. Throughout study phase 2, blood samples were collected for CBC determination and serum biochemical analysis.

Results—Plasma concentrations of AZA and its metabolite, 6-MP, decreased rapidly from plasma following IV administration of AZA, consistent with the short mean elimination half-life of 1.8 minutes. Oral bioavailability of AZA was low, ranging from 1% to 7%. No horses had abnormalities on CBC determination or serum biochemical analysis, other than 1 horse that was lymphopenic on day 5 and 26 of daily treatment. This horse developed facial alopecia from which 1 colony of a Trichophyton sp was cultured; alopecia resolved within 1 month after the study ended.

Conclusions and Clinical Relevance—Overall, no adverse effects were observed with long-term oral administration of AZA to horses, although 1 horse did have possible evidence of immunosuppression with chronic treatment. Further investigation of the clinical efficacy of AZA in the treatment of autoimmune diseases in horses is warranted. (Am J Vet Res 2005;66:1578–1583)

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in American Journal of Veterinary Research
History

A 2-year-old castrated male Dachshund was evaluated at a veterinary medical teaching hospital because of progressive lethargy, anorexia, severe generalized erythema, urticaria, and angioedema of 8 days’ duration. There had been no response to prior treatment with anti-inflammatory doses of corticosteroids, broad-spectrum antimicrobials, IV fluid therapy, antihistamines, and antacids. Two days prior to the referral evaluation, skin biopsy specimens were obtained for histologic examination, the results of which were pending at the time of the referral examination. Immediately prior to the referral evaluation, the dog developed marked non-weight-bearing lameness of the left pelvic limb and became acutely hypothermic with

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in Journal of the American Veterinary Medical Association
in Journal of the American Veterinary Medical Association