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 determine pharmacokinetics of
clomipramine and its principle metabolite (desmethylclomipramine)
in the plasma of dogs after IV or oral
administration of a single dose.
Animals—6 male and 6 female Beagles.
Procedures—Clomipramine was administered IV
(2 mg/kg), PO (4 mg/kg) after food was withheld for 15
hours, and PO (4 mg/kg) within 25 minutes after dogs
were fed. Plasma clomipramine and desmethylclomipramine
concentrations were measured by use
of a gas chromatography with mass-selection method.
Results—Time to peak plasma concentrations of
clomipramine and desmethylclomipramine following
oral administration was 1.2 hours. For clomipramine,
after IV administration, elimination half-life was 5 hours,
mean residence time was 3 hours, and plasma clearance
was 1.4 L/h/kg. Values for mean residence time
and terminal half-life following oral administration were
similar to values obtained following IV administration,
and systemic bioavailability was approximately 20% for
clomipramine and 140% for desmethylclomipramine,
indicating fast absorption of clomipramine from the gastrointestinal
tract and extensive first-pass metabolism.
Administration of clomipramine with food did not alter
the area under the concentration versus time curve for
desmethylclomipramine but resulted in a 25% increase
for clomipramine. Clomipramine and desmethylclomipramine
were extensively bound (> 96%) to
serum proteins. There were no significant differences
in area under the concentration versus time curve
between male and female dogs.
Conclusions and Clinical Relevance—Results indicate
that there should not be any clinically important
differences in efficacy regardless of whether
clomipramine is administered with or without food.
(Am J Vet Res 2000;61:74–79)
Objective—To determine pharmacokinetics of
clomipramine and its principle metabolite (desmethylclomipramine)
in the plasma of dogs following singledose
and repeated-dose oral administration at various
Animals—9 male and 9 female Beagles.
Procedures—Clomipramine was administered orally
at a dose of 1, 2, or 4 mg/kg to 3 male and 3 female
dogs, first as a single dose and then, after an interval
of 14 days, twice daily for 10 days. Plasma
clomipramine and desmethylclomipramine concentrations
were measured by use of a gas chromatography
with mass-selection method.
Results—Dose-related accumulation was detected following
repeated-dose administration. Accumulation
ratios after administration of clomipramine at dosages
of 1, 2, and 4 mg/kg twice daily were 1.4, 1.6, and 3.8,
respectively, for clomipramine and 2.1, 3.7, and 7.6,
respectively, for desmethylclomipramine. Terminal
half-life increased slightly (1.6-fold for clomipramine
and 1.2-fold for desmethylclomipramine) with repeated-
dose administration but remained short in all groups
(≤ 4 hours). Steady state was reached within 4 days in
all animals. Ratios of the areas under the concentration
versus time curves from time 0 to 12 hours for
clomipramine and desmethylclomipramine were 3.9,
3.1, and 1.5 after repeated administration at dosages
of 1, 2, and 4 mg/kg every 12 hours, respectively.
Areas under the concentration versus time curve,
mean residence times, and terminal half-lives were not
significantly different between male and female dogs.
Conclusions and Clinical Relevance—Repeated
administration of clomipramine results in higher concentrations
of clomipramine than desmethylclomipramine
in dogs. (Am J Vet Res 2000;61:80–85)
Objective—To determine the effects of clomipramine
hydrochloride on heart rate and rhythm in dogs.
Animals—17 healthy Beagles.
Procedures—In experiment 1, 8 dogs received
placebo or clomipramine (20 mg/kg of body weight,
q 24 h, PO) for 7 days in a 2-way crossover design.
In experiment 2, 9 dogs were evaluated for 48
hours before and 24 hours after oral administration
of clomipramine (4 or 12 mg/kg) in a 2-way
crossover design. Electrocardiogram and heart rate
were monitored continuously by use of telemetry.
Results—A significant diurnal rhythm in heart rate
was detected; minimum values were recorded at
night. Administration of 20 mg of clomipramine/kg
induced a significant reduction in heart rate,
with peak effect achieved approximately 12
hours after dosing. Administration of 4 or 12 mg of
clomipramine/kg did not result in significant changes in
heart rate. Sinoatrial and second-degree atrioventricular
block and ventricular escape beats were
observed during periods of slow heart rate in more
dogs that received clomipramine (3 to 4 of 8 dogs),
compared with dogs that received placebo (1 to 2 of
8 dogs), but this difference was not significant.
Conclusions and Clinical Relevance—Short-term
administration of clomipramine induced benign
cardiovascular effects in dogs rather than the
potentially dangerous arrhythmias or tachycardia
reported following administration of tricyclic antidepressants
to humans. Precautions regarding
cardiovascular effects may not be needed for the use
of clomipramine in healthy dogs. (Am J Vet Res
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 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.
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