日本小児循環器学会雑誌 Pediatric Cardiology and Cardiac Surgery

Since 1976, patent ductus arteriosus (DA) in the premature infants has been treated with cyclooxygenase inhibitors with some success. In 1993, Nakanishi discovered that DA strips in rabbit fetuses could be constricted with glibenclamide, an anti-diabetic sulfonylurea drug. In fetal rats with direct fetal administration and whole-body freezing, glibenclamide constricts the DA dose-dependently. In the near-term fetus, DA constriction is mild and the inner diameter was shortened up to 30％ with 1 mg/kg glibenclamide (a clinical dose for children with diabetes with Kir 6.2 mutations). The fetal DA closes completely with 100 mg/kg glibenclamide. Following the administration of indomethacin, glibenclamide induced the same additional DA constriction in both near-term and preterm fetuses. In 1-day-old neonatal rats under maternal feeding, orogastric administration of large doses (up to 100 mg/kg) of glibenclamide induced hypoglycemia over 3 days with blood glucose levels of about 30 mg/dL. All of the neonates showed intact survival with good body weight gain and normal blood parameters. These findings suggest that glibenclamide at doses of 1 mg/kg and lhigher, with concomitant administration of glucose to prevent hypoglycemia, is useful for the closure of patent DA in the premature infants following unsuccessful treatment with indomethacin.