Uterine relaxant effects of cyclooxygenase-2 inhibitors in vitro

OBJECTIVE: To compare the effects of three cyclooxygenase-2 (COX-2) inhibitors: nimesulide, meloxicam, and celecoxib, which exhibit varying COX-2 selectivity, on contractile activity in pregnant (before and after labor) and nonpregnant human myometrial tissue in vitro. METHODS: Isometric tension recording was performed under physiologic conditions in isolated myometrial strips obtained from 33 women undergoing hysterectomy or either elective or emergency cesarean section. The effects of cumulative additions of nimesulide, meloxicam, and celecoxib (between 1 nmol/L and 100 μmol/L) on myometrial contractility were measured, and values for -log₁₀ EC₅₀ and mean maximal inhibition were compared. RESULTS: Nimesulide, meloxicam, and celecoxib exerted significant relaxant effects on contractility in nonpregnant, pregnant nonlabor, and pregnant labor myometrial strips. Values for -log₁₀ EC₅₀ values (± standard error of the mean) were as follows: nimesulide (nonpregnant) 5.14±0.93 (n=6), (pregnant nonlabor) 4.91±0.75 (n=6), and (pregnant labor) 5.84±0.35 (n=6); meloxicam (nonpregnant) 6.53±0.57 (n=6), (pregnant nonlabor) 4.80±0.71 (n=6), and (pregnant labor) 5.62±0.21 (n=6); celecoxib (nonpregnant) 6.15±0.99 (n=6), (pregnant nonlabor) 7.08±0.98 (n=6), and (pregnant labor) 7.25±0.99 (n=3). Celecoxib exhibited greater potency than nimesulide or meloxicam (P < .01). The range of maximal relaxation values achieved in the three tissue types were as follows: nimesulide 68-70% (n=18; P < .01), meloxicam 69-84% (n=18; P < .01), and celecoxib 69-77% (n=15; P < .01). CONCLUSION: COX-2 inhibitors exert significant relaxation in human myometrium with a similar potency in nonpregnant and pregnant (before and after labor onset) tissues. Celecoxib, a COX-2 specific inhibitor, was more potent than nimesulide or meloxicam, COX-2 preferential inhibitors.