Abstract
Background: Sulfonylureas (tolbutamide = Rastinon, glibenclamide = glyburide, glimepiride = Amaryl) inhibit KATP channels and induce release of insulin. In in-vitro studies, glibenclamide constricts the ductus arteriosus. Placental transport of sulfonylureas is variable; high with tolbutamide, and low with glibenclamide, respectively.
Purpose: To clarify the in-vivo ductus constrictive effects of various sulfonylureas.
Methods: Sulfonylureas were administered orogastrically to pregnant near-term (21FD) or preterm (19FD) Wistar rats. Fetal ductus arteriosus was studied 2, 4, 8 and 24 hours later, with a rapid whole-body freezing method and measurement of the inner diameter of the ductus.
Results: Tolbutamide constricted the fetal ductus dose-dependently. With clinical dose (10 and 30 mg/kg), the near-term fetal ductus constricted moderately, and the ductal diameter decreased to 0.8 and 0.5 compared to the control four hours later. With a large dose (100 mg/kg), the fetal ductus constricted severely, and the diameter decreased to 0.2 compared to the control four hours later. Tolbutamide constricted the pre-term ductus comparatively less. Glimepiride with a large dose of 10 mg/kg constricted the near-term fetal ductus only mildly. With a large dose of glibenclamide (10 mg/kg), it did not constrict the near-term or the preterm ductus arteriosus, reflecting poor placental transport.
Conclusion: Clinical doses of tolbutamide constrict the fetal ductus moderately. With a 10 times larger dose, the ductus closes completely. Experimental comparison suggests tolbutamide is more potent constrictor of the fetal ductus than indomethacin, and can be used to close a premature PDA in the rat model.
FD = Fetal Days.
Article PDF
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Momma, K., Toyoshima, K., Hayama, E. et al. 474 Hypoglycemic Agents Sulfonylureas Constrict the Fetal Ductus Arteriosus in the Rat. Pediatr Res 68 (Suppl 1), 242–243 (2010). https://doi.org/10.1203/00006450-201011001-00474
Issue Date:
DOI: https://doi.org/10.1203/00006450-201011001-00474