GA: Marked interindividual variability in the response to selective inhibitors of cyclooxygenase-2. Gastroenterology 2006

may influence both efficacy and safety. Cyclooxygenase (COX)-2 inhibitors pose a cardiovascular risk by poten-tially increasing the likelihood of thrombosis, hyperten-sion, and atherogenesis. Differences between individu-als in the response to COX-2 inhibitors would be expected to influence their susceptibility to cardiovascu-lar complications. We examined the variability in degree and selectivity of COX-2 inhibition in humans in re-sponse to celecoxib and rofecoxib. Methods: Fifty healthy volunteers received placebo, rofecoxib (25 mg), and celecoxib (200 mg), randomized by order. COX-1 and COX-2 inhibition was determined using ex vivo and in vivo indices of enzymatic activity. A subset of 5 indi-viduals underwent 5 replicate studies to estimate vari-ability in drug response both within and between sub