Variability in the response to cyclooxygenase inhibitors: toward the individualization of nonsteroidal anti-inflammatory drug therapy.

Nonsteroidal anti-inflammatory drugs (NSAIDs) relieve pain, inflammation, and fever by inhibiting cyclooxygenases (COXs). Nonsteroidal anti-inflammatory drugs selective for COX-2 were developed to inhibit the major enzymatic source of the prostaglandins that mediate pain and inflammation while sparing COX-1-derived prostaglandins that contribute dominantly to gastric cytoprotection. Indeed, such purpose-designed COX-2 inhibitors reduced the incidence of serious gastrointestinal adverse effects when compared with traditional NSAIDs; however, they confer a small but absolute cardiovascular hazard. The hazard might also extend to traditional NSAIDs, which are relatively selective for COX-2, such as diclofenac, meloxicam, and etodolac. The occurrence of complications and the therapeutic responses to individual NSAIDs may vary substantially from patient to patient. Exploitation of detectable variability in the biochemical response to NSAIDs may offer an approach to the personalization of the management of risk and benefit.