“…The importance of COX isoform selectivity relates to risk of adverse reactions, particularly associated with COX-1-mediated gastro-intestinal upsets, perforation and associated peritonitis, that have been reported in monogastrics [ 257 , 258 , 259 , 260 , 261 , 262 ] and it was assumed that a COX-2 selective agent would be free of such adverse effects. However, adverse cardiovascular, intestinal and other effects have been reported in humans or dogs associated with some COX-2 selective NSAIDs [ 259 , 262 , 263 , 264 , 265 , 266 , 267 , 268 , 269 , 270 , 271 , 272 , 273 , 274 , 275 , 276 , 277 , 278 , 279 , 280 , 281 , 282 , 283 , 284 , 285 , 286 ]. It is important to note here that COX-selectivity is a continuum, so an agent that is described as ‘COX-2 selective’ still has effects on COX-1, but the effects on COX-2 are evident at lower dose rates than the effects on COX-1 [ 275 , 276 ].…”