Uterine relaxant effects of cyclooxygenase-2 inhibitors in vitro

OBJECTIVE: To compare the effects of three cyclooxygenase-2 (COX-2) inhibit ors: nimesulide, meloxicam, and celecoxib, which exhibit varying COX-2 sele ctivity, on contractile activity in pregnant (before and after labor) and n onpregnant human myometrial tissue in vitro. METHODS: Isometric tension recording was performed under physiologic condit ions in isolated myometrial strips obtained from 33 women undergoing hyster ectomy or either elective or emergency cesarean section. The effects of cum ulative additions of nimesulide, meloxicam, and celecoxib (between 1 nmol/L and 100 mu mol/L) on myometrial contractility were measured, and values fo r -log(10) EC50 and mean maximal inhibition were compared. RESULTS: Nimesulide, meloxicam, and celecoxib exerted significant relaxant effects on contractility in nonpregnant, pregnant nonlabor, and pregnant la bor myometrial strips. Values for -log(10) EC50 values (+/- standard error of die 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 non labor) 4.80 +/- 0.71 (n = 6), and (pregnant labor) 5.62 +/- 0.21 (n = 6); c elecoxib (nonpregnant) 6.15 +/- 0.99 (n = 6), (pregnant nonlabor) 7.08 +/- 0.98 (n = 6), and (pregnant labor) 7.25 k 0.99 (n = 3). Celecoxib exhibited greater potency than nimesulide or meloxicam (P < .01). The range of maxim al relaxation values achieved in the three tissue types were as follows: ni mesulide 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 myometri um with a similar potency in nonpregnant and pregnant (before and after lab or onset) tissues. Celecoxib, a COX-2 specific inhibitor, was more potent t han nimesulide or meloxicam, COX-2 preferential inhibitors. (C) 2001 by the American College of Obstetricians and Gynecologists.