Response of fetal prostanoids, nitric oxide, and ductus arteriosus to the short- and long-term antenatal administration of celecoxib, a selective cyclo-oxygenase-2 inhibitor, in the pregnant rabbit.
OBJECTIVE
The purpose of this study was to test the hypothesis that the maternal administration of therapeutic doses of celecoxib would not affect ductus arteriosus patency or alter renal and hepatic prostanoids in the fetal rabbit.


METHODS
Pregnant rabbits received celecoxib from 13 to 20 days (celecoxib-A), from 13-28 days (celecoxib-B), or vehicle from 13 to 28 days by gavage. Fetal serum and lung tissue were analyzed for nitric oxide oxidation products. Fetal plasma, liver, and kidney were analyzed for prostaglandin levels.


RESULTS
The ductus arteriosus was patent in both treatment groups. Celecoxib induced elevations of plasma prostaglandin E(2) production. In celecoxib-B liver and kidney, the 6-keto-prostaglandin F(1alpha) and prostaglandin F(2alpha) levels were increased, and the prostaglandin E(2) and thromboxane B(2) levels were decreased substantially.


CONCLUSIONS
This preliminary evaluation demonstrates that the maternal administration of celecoxib does not influence fetal ductus arteriosus patency adversely in rabbits.
Hausman
Nicole
N
Division of Maternal-Fetal Medicine, Women's Hospital, Long Beach Memorial Medical Center, 2801 Atlantic Avenue, Long Beach, CA 90801-1428, USA.
Beharry
Kay
K
Nishihara
Kenji
K
Akmal
Yasir
Y
Stavitsky
Yuri
Y
Asrat
Tamerou
T
D000704:Analysis of Variance; D000818:Animals; D000068579:Celecoxib; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004334:Drug Administration Schedule; D004373:Ductus Arteriosus / Q000187:drug effects*; D005260:Female; D005333:Fetus / Q000187:drug effects; D009569:Nitric Oxide / Q000032:analysis* / Q000378:metabolism; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000187:drug effects*; D011336:Probability; D011453:Prostaglandins / Q000032:analysis* / Q000378:metabolism; D011720:Pyrazoles; D011817:Rabbits; D012016:Reference Values; D018570:Risk Assessment; D012680:Sensitivity and Specificity; D013449:Sulfonamides / Q000494:pharmacology*
D016861:Cyclooxygenase Inhibitors; D011453:Prostaglandins; D011720:Pyrazoles; D013449:Sulfonamides; D009569:Nitric Oxide; D000068579:Celecoxib