Pharmacokinetic and pharmacodynamic aspects of the ideal COX-2 inhibitor: a rheumatologist's perspective

The ideal cyclooxygenase-2-specific inhibitor (coxib) would demonstrate eff icacy comparable or superior to the best non-steroidal anti-inflammatory dr ug (NSAID) and, in addition to being substantially less gastrotoxic than th e safest conventional NSAID, would have limited or no cardiovascular or ren al toxicity and be generally tolerated as well as placebo. The contribution of the pharmacokinetic properties of a coxib to achieving this goal has be en overlooked to some degree for available coxibs. Maximizing synovial comp artment exposure while minimizing systemic exposure may deliver tolerabilit y benefits, particularly with respect to rates of hypertension and cardiova scular and thrombotic adverse effects.