Increased constriction of the ductus arteriosus by dexamethasone, indomethacin, and rofecoxib in fetal rats.
BACKGROUND
To find a better treatment for patent ductus arteriosus (PDA) in premature infants, the present study investigated the synergism of clinical doses of dexamethasone, indomethacin, and rofecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor, on the fetal ductus arteriosus (DA) in rats.


RESULTS
Dexamethasone (0.3 mg/kg), indomethacin (0.3 mg/kg), and rofecoxib (0.3 mg/kg), alone or in combination, were administered to preterm (d19) and near-term (d21) fetal rats. The ratio of the inner diameter of the DA to that of the main pulmonary artery (PA) (DA/PA) was studied at 2, 4 and 8 h after drug administration, using a rapid whole-body freezing method. In near-term rats, the combined administration of dexamethasone and indomethacin caused severe constriction, with a DA/PA ratio of 0.52+/-0.08 at 8 h, whereas the DA/PA ratios were 0.83+/-0.03 and 0.90+/-0.02 with dexamethasone and indomethacin, respectively. Combined administration of dexamethasone and rofecoxib also caused severe constriction, with a DA/PA ratio of 0.64+/-0.07 at 8 h, compared with the DA/PA ratio of 0.92+/-0.03 with rofecoxib alone.


CONCLUSIONS
Combined therapy may be an option in the medical management of PDA in premature infants before considering surgical treatment.
Takami
Takeshi
T
Department of Pediatrics, Tokyo Medical University, Japan. t-takami@k8.dion.ne.jp
Momma
Kazuo
K
Imamura
Shinichiro
S
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage*; D003907:Dexamethasone / Q000008:administration & dosage; D004353:Drug Evaluation, Preclinical; D004359:Drug Therapy, Combination; D004373:Ductus Arteriosus / Q000187:drug effects* / Q000502:physiology; D004374:Ductus Arteriosus, Patent / Q000188:drug therapy; D005333:Fetus / Q000098:blood supply / Q000187:drug effects*; D007213:Indomethacin / Q000008:administration & dosage; D007783:Lactones / Q000008:administration & dosage; D023421:Models, Animal; D051381:Rats; D017208:Rats, Wistar; D013450:Sulfones / Q000008:administration & dosage; D014661:Vasoconstriction / Q000187:drug effects*
D000893:Anti-Inflammatory Agents; D007783:Lactones; D013450:Sulfones; C116926:rofecoxib; D003907:Dexamethasone; D007213:Indomethacin