Objective—To develop and validate in cats suitable in
vitro assays for screening and ranking nonsteroidal antiinflammatory
drugs (NSAIDs) on the basis of their
inhibitory potencies for cyclooxygenase (COX)-1 and
Procedure—COX-1 and COX-2 activities in heparinized
whole blood samples were induced with calcium
ionophore and lipopolysaccharide, respectively. For the
COX-2 assay, blood was pretreated with aspirin. The
COX-1 and COX-2 assays were standardized, such that
time courses of incubation with the test compounds
and conditions of COX expression were as similar as
possible in the 2 assays. Inhibition of thromboxane B2
production, measured by use of a radioimmunoassay,
was taken as a marker of COX-1 and COX-2 activities.
These assays were used to test 10 to 12 concentrations
of a COX-1 selective drug (SC-560) and of 2
NSAIDs currently used in feline practice, meloxicam
and carprofen. Selectivities of these drugs were compared
by use of classic 50% and 80% inhibitory concentration
(ie, IC50 and IC80) ratios but also with alternative
indices that are more clinically relevant.
Results—These assay conditions provide a convenient
and robust method for the determination of NSAID
selectivity. The S(+) enantiomeric form of carprofen
was found to be COX-2 selective in cats, but meloxicam
was only slightly preferential for this isoenzyme.
Conclusions and Clinical Relevance—In vitro pharmacodynamic
and in vivo pharmacokinetic data predict
that the COX-2 selectivity of both drugs for cats
will be limited when used at the recommended
doses. This study provides new approaches to the
selection of COX inhibitors for subsequent clinical
testing. (Am J Vet Res 2005;66:700–709)
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.