Efficacy of the selective prostaglandin synthase type 2 inhibitor nimesulide in blocking basal prostaglandin production and delaying glucocorticoid-induced premature labor in sheep

OBJECTIVE: The purpose of the study was to determine the effects of selecti ve prostaglandin synthase type 2 inhibitors on basal prostaglandin concentr ations in the fetal and maternal circulations and on the labor-associated i ncrease in prostaglandin production in sheep. STUDY DESIGN: The effects of maternal nimesulide (0.01, 0.1, and 1 mg/kg) a nd 6-methoxy-2-naphthylacetic acid (1, 5, and 10 mg/kg) administration were examined (n = 5) at 134 +/- 1 days' gestation. At 138 days' gestation prem ature labor was induced by fetal dexamethasone infusion (1 mg/d). Ewes were treated with either vehicle or nimesulide infusion (20 mg.d(-1).kg(-1), n = 5 per group). RESULTS: Nimesulide and 6-methoxy-2-naphthylacetic acid decreased basal pro staglandin production in a concentration-dependent manner. Delivery of nime sulide-treated ewes was delayed by greater than or equal to 17 hours with r espect to that of control ewes (53.9 +/- 2.6 hours). In 2 nimesulide-treate d ewes labor did not progress to delivery despite membrane rupture. The inc rease in prostaglandin concentrations usually seen during dexamethasone-ind uced labor was abolished in nimesulide-treated ewes and also in their fetus es. CONCLUSIONS: Highly selective inhibitors of prostaglandin endoperoxidase H synthase 2 may be required to spare fetal prostaglandin production and limi t potential side effects during the suppression of preterm labor. (Am J Obs tet Gynecol 1999;180:1244-53.).