Objective—To determine efficacy and safety of
cyclosporine in the treatment of atopic dermatitis
among dogs in North America.
Design—Randomized controlled (phase 1) and openlabel
(phase 2) trials.
Animals—268 dogs with atopic dermatitis.
Procedure—In phase 1, dogs were randomly assigned
to be treated with cyclosporine (5 mg/kg [2.3 mg/lb],
PO, q 24 h) or a placebo. In phase 2, all dogs were
treated with cyclosporine for 16 weeks. Frequency of
cyclosporine administration was decreased if dogs
Results—At the end of phase 1, canine atopic dermatitis
extent and severity index (CADESI) scores for
dogs treated with cyclosporine were significantly
lower than scores for control dogs. Percentage of
dogs with severe pruritus decreased from 67% to
16% for the cyclosporine group but from 66% to only
61% for the control group. During phase 2,
cyclosporine dosage was decreased to every-otherday
administration in 39% of the dogs after 4 weeks.
After 12 weeks, 22% of the dogs were treated twice
weekly and 36% were treated every other day. After
16 weeks, CADESI score had decreased > 50% in
68% of the dogs and 47% of dogs had no or mild pruritus.
The most frequent adverse reactions were gastrointestinal
Conclusions and Clinical Relevance—Results suggest
that cyclosporine is efficacious for the treatment
of atopic dermatitis in dogs and that frequency of
cyclosporine administration can be reduced following
an initial induction period. The drug was well tolerated.
(J Am Vet Med Assoc 2005:226:1855–1863)
Objective—To assess efficacy and tolerability of robenacoxib for control of pain and inflammation in dogs undergoing orthopedic surgery.
Animals—140 client-owned dogs.
Procedures—A multicenter, prospective, randomized, blinded field trial was conducted to compare robenacoxib (97 dogs) and meloxicam (43 dogs). After randomization, each dog received an initial dose (robenacoxib, 2 mg/kg; meloxicam, 0.2 mg/kg) via SC injection before surgery and daily doses (robenacoxib, 1 to 2 mg/kg; meloxicam, 0.1 mg/kg) administered orally for up to 15 days after surgery. Efficacy was assessed by veterinarians and owners via numeric rating scales and visual analogue scales. Safety was assessed on the basis of reported adverse events, clinical signs, results of hematologic and biochemical analyses, and buccal mucosa bleeding times.
Results—Treatment groups were balanced with respect to baseline and demographic data. Both treatments provided similar adequate pain control, as assessed with a modified Glasgow pain scale as the primary end point and supported by secondary end points in evaluations conducted by veterinarians and owners. For the primary end point, the ratio of the reciprocal of the scores for robenacoxib to meloxicam was 1.16 (95% confidence interval, 0.98 to 1.37). No dogs required rescue analgesia. Both treatments were associated with only minor adverse events, which were not necessarily related to the administered treatments and did not affect mucosal bleeding times.
Conclusions and Clinical Relevance—Robenacoxib provided efficacy and tolerability similar to those of meloxicam for the management of perioperative pain and inflammation in dogs undergoing orthopedic surgery.
Objective—To evaluate a model for atopic dermatitis
(AD) and to measure the effect of sensitization in
Beagles genetically predisposed to produce high
serum concentrations of allergen specific IgE.
Animals—22 laboratory Beagles.
Procedure—Seventeen dogs were sensitized from
birth to 3 allergens (recombinant birch pollen,
Dermatophagoides pteronyssinus, and D farinae).
Five nonsensitized dogs from the same litters served
as controls. Clinical scoring, regular intradermal testing,
measurement of serum concentrations of allergen-specific IgE, and collection of biopsy specimens
of skin at 23, 32, and 43 weeks of age were performed.
Serial tissue sections were stained for identification
of IgE+ cells, mast cells and their subtypes, T-cells,
Langerhans cells, and major histocompatibility
complex class-II+ cells. At the age of 15 months,
dogs were continuously exposed to 2 µg of mite allergen/
g of dust.
Results—Sensitized dogs had positive intradermal
test reactions and significantly higher serum concentrations
of allergen specific IgE, compared with nonsensitized
dogs. In sensitized and nonsensitized
dogs, a significantly higher number of mast cells was
found at predilection sites, compared with the control
biopsy site. The number of mast cells at predilection
sites increased with age. Sensitization significantly
increased the number of epidermal Langerhans cells
by 23 weeks of age. The number of epidermal
Langerhans cells significantly increased in nonsensitized
dogs by 32 weeks of age. Clinical scoring only
revealed mild transient erythema in some dogs.
Conclusion and Clinical Relevance—Increases in concentrations of serum allergen-specific IgE and exposure to allergens is not
sufficient to induce clinical signs of AD in genetically
predisposed dogs. (Am J Vet Res 2002;63:1329–1336)
Objective—To compare the analgesic and anti-inflammatory
effect of single doses of carprofen, etodolac,
meloxicam, and butorphanol in dogs with induced
acute synovitis (acute pain model) via kinetic gait
analysis and orthopedic evaluation and examine measurement
of serum C-reactive protein (CRP) concentration
as an indicator of treatment efficacy.
Animals—12 Beagles and 6 additional Beagles that
were used only in serum CRP analyses.
Procedure—Acute synovitis was induced in right stifle
joints of dogs via intra-articular injection of
monosodium urate solution. Treatments included
butorphanol (0.2 mg/kg, IV), carprofen (4 mg/kg, PO),
etodolac (17 mg/kg, PO), or meloxicam (0.2 mg/kg,
PO); control dogs received no treatment. The procedure
was repeated (3-week intervals) until all dogs
received all treatments including control treatment.
Lameness was assessed on a biomechanical force
platform and via orthopedic evaluations of the stifle
joints; blood was collected to monitor serum CRP
Results—Compared with control dogs, treated dogs
had significantly different vertical ground reaction
forces and weight-bearing scores. Greatest improvement
in lameness was observed in carprofen-treated
dogs. Etodolac had the fastest onset of action.
Compared with butorphanol treatment, only carprofen
and etodolac were associated with significantly
lower pain scores. An increase in serum CRP concentration
was detected after intra-articular injection in all
dogs; this change was similar among groups.
Conclusions and Clinical Relevance—Carprofen,
etodolac, and meloxicam had greater efficacy than
butorphanol in relief of acute pain. Carprofen was
most effective overall. In this acute pain model, serum
CRP analysis was not useful to assess drug efficacy.
(Am J Vet Res 2003;64:1429–1437)
Objective—To evaluate the efficacy and tolerability of oral administration of robenacoxib for treatment of acute pain and inflammation associated with musculoskeletal disorders in cats.
Animals—155 cats requiring relief of signs of pain and inflammation associated with acute musculoskeletal disorders.
Procedures—The study was a multicenter, prospective, randomized, masked, noninferiority field trial. Cats were allocated randomly to 1 of 3 treatment groups: group 1 (1.0 to 2.4 mg of robenacoxib/kg, q 24 h), group 2 (1.0 to 2.4 mg of robenacoxib/kg, q 12 h [daily dosage, 2.0 to 4.8 mg/kg]), and group 3 (ketoprofen [mean dosage, 1 mg/kg, q 24 h]). All cats were administered tablets PO for 5 or 6 days. The primary efficacy endpoint was the investigator global assessment score, which was the sum of scores of signs of pain, inflammation, and mobility assessed in a masked manner by veterinary investigators at baseline, day 2, and day 4 or 5. Cat owners monitored in a nonmasked manner secondary responses by observation of cats’ activity, behavior, appetite, and interactions. Safety was assessed by monitoring adverse events, clinical signs, and hematologic and plasma biochemical variables (before and after treatment).
Results—No significant differences were detected among the 3 treatment groups for any primary or secondary efficacy endpoints or for tolerability variables. Robenacoxib tablets administered once daily were significantly more palatable than ketoprofen tablets.
Conclusions and Clinical Relevance—Robenacoxib tablets administered once daily had noninferior efficacy and tolerability, and superior palatability, compared with the active control drug, ketoprofen, for the treatment of signs of acute pain and inflammation associated with musculoskeletal disorders in cats.
Objective—To establish pharmacokinetics of robenacoxib after administration to cats via the IV, SC, and oral routes.
Procedures—In a crossover design, robenacoxib was administered IV, SC, and orally (experiment 1) and orally (experiment 2) to cats with different feeding regimens. Blood robenacoxib concentrations were assayed, with a lower limit of quantification of 3 ng/mL.
Results—In experiment 1, geometric mean pharmacokinetic values after IV administration of robenacoxib were as follows: blood clearance, 0.44 L/kg/h; plasma clearance, 0.29 L/kg/h; elimination half-life, 1.49 hours; and volume of distribution at steady state (determined from estimated plasma concentrations), 0.13 L/kg. Mean bioavailability was 69% and median time to maximum concentration (Cmax) was 1 hour for cats after SC administration of robenacoxib, whereas mean bioavailability was 49% and 10% and median time to Cmax was 1 hour and 30 minutes after oral administration to cats after food withholding and after cats were fed their entire ration, respectively. In experiment 2, geometric mean Cmax was 1,159, 1,201, and 692 ng/mL and area under the curve from 0 to infinity was 1,337, 1,383, and 1,069 ng × h/mL following oral administration to cats after food withholding, cats fed one-third of the daily ration, and cats fed the entire daily ration, respectively.
Conclusions and Clinical Relevance—For treatment of acute conditions in cats, it is recommended to administer robenacoxib by IV or SC injection, orally after food withholding, or orally with a small amount of food to obtain optimal bioavailability and Cmax.
Objective—To evaluate effects of zoledronate on
markers of bone metabolism in dogs after transection
of the cranial cruciate ligament (CrCL).
Animals—21 adult dogs.
Procedure—Unilateral CrCL transection was performed
arthroscopically. Dogs were allocated to 3
groups (control group, low-dose zoledronate
[10 µg/kg, SC, q 90 d for 12 months], and high-dose
zoledronate [25 µg/kg, SC, q 90 d for 12 months]).
Serum osteocalcin (OC), serum bone-specific alkaline
phosphatase (BAP), and urine pyridinoline and
deoxypyridinoline concentrations were measured at
0, 1, 3, 6, 9, and 12 months after surgery. Bone mineral
density (BMD) was determined in the distal portion
of the femur and proximal portion of the tibia via
computed tomography at each time point. Data were
analyzed by a repeated-measures ANOVA.
Results—Zoledronate inhibited OC in the high-dose
group at 9 and 12 months and at 12 months in the low-dose
group, compared with the control group. High-dose
zoledronate decreased BAP concentrations 3 and 9
months after surgery. In the control group, BMD was
decreased in the femoral condyle and caudal tibial
plateau. Zoledronate prevented significant BMD decreases
starting 1 month after transection, compared with
control dogs. In the caudomedial aspect of the tibial
plateau, both zoledronate groups had significant increases
in BMD after 3 months, compared with control dogs.
Conclusions and Clinical Relevance—Zoledronate
may reduce subchondral bone loss and effect markers
of bone metabolism in dogs with experimentally
induced instability of the stifle joint and subsequent
development of osteoarthritis. (Am J Vet Res
OBJECTIVE To evaluate whether anti-inflammatory doses of cyclosporine activate Toxoplasma gondii in chronically infected cats or potentiate infection in cats exposed for the first time.
ANIMALS 30 T gondii–negative cats.
PROCEDURES Cats were assigned to 1 of 3 groups (10 cats/group). Group 1 (control) cats were administered a placebo for 126 days; group 2 cats were administered a placebo for 84 days, followed by cyclosporine at 7.5 mg/kg/d, PO, for 42 days; and group 3 cats were administered cyclosporine at 7.5 mg/kg/d, PO, for 126 days. Cats were orally inoculated with T gondii on day 42. Results for fecal flotations, PCR assays, and histologic examinations and IgM and IgG titers were analyzed. Cyclosporine concentrations were measured on selected days.
RESULTS All cats were infected by T gondii and developed signs of self-limiting gastrointestinal tract infection. Group 3 had the highest incidence and severity of CNS and pulmonary histopathologic findings typical of toxoplasmosis. One cat in group 3 died of systemic toxoplasmosis; that cat had a cyclosporine concentration of 1,690 ng/mL. Group 2 cats infected with T gondii before cyclosporine administration did not have repeated oocyst shedding. Group 3 cats shed fewer oocysts for a shorter time than did control cats of group 1.
CONCLUSIONS AND CLINICAL RELEVANCE Oral administration of cyclosporine in accordance with the protocol for this study did not potentiate the enteroepithelial phase of T gondii infection. Cats with high cyclosporine blood concentrations at the time of primary T gondii infection may be at risk of developing systemic toxoplasmosis.
Procedure—Cats with a minimum 1-month history of
spraying urine against vertical surfaces at least twice
per week were randomly assigned to be treated with
a placebo or with clomipramine at a dosage of 0.125
to 0.25 mg/kg (0.057 to 0.11 mg/lb), 0.25 to 0.5 mg/kg
(0.11 to 0.23 mg/lb), or 0.5 to 1 mg/kg (0.23 to 0.45
mg/lb), PO, every 24 hours for up to 12 weeks.
Owners of all cats were given information on behavioral
treatment and environmental modification.
Results—Prior to treatment, mean number of urine
spraying events ranged from 0.9 to 1.3 urine spraying
events/d for the 4 groups, and mean percentage of
days with urine spraying events ranged from 62% to
69%. All 3 dosages of clomipramine were associated
with significant reductions in frequency of urine
spraying. Sedation was the most common adverse
effect and was identified in 27 of the 50 cats treated
with clomipramine; however, treatment was not discontinued
in any cat because of sedation.
Conclusions and Clinical Relevance—Results of the
present study suggest that compared with a placebo,
clomipramine significantly reduces the frequency of
urine spraying in cats in terms of the number of urine
spraying events per day and the number of days with
urine spraying events. For cats with urine spraying,
the recommended initial dosage of clomipramine is
0.25 to 0.5 mg/kg, PO, every 24 hours. (J Am Vet Med