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.
12 healthy adult horses.
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).
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.
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
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)
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
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.
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.
Results–S 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)
Objective—To determine pharmacokinetics of azathioprine
(AZA) and clinical, hematologic, and serologic
effects of IV and oral administration of AZA in 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
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