Placental Transfer of Theophylline: Two Case Reports

Abstract

The placental transfer of xanthine compounds such as caffeine and theophylline has only recently been recognized. By measuring serum theophylline concentrations in two mothers and their neonates at delivery, we have attempted to determine the extent and significance of placental theophylline transfer to the fetus. At delivery, the two maternal serum theophylline concentrations were 13 µg/ml and 11 µg/ml, and cord serum contained 12 µg/ ml and 11 µg/ml of theophylline, respectively. In our first case, the neonatal theophylline concentration at delivery was not reported, but a concentration of 13 µg/ml was obtained six hours after delivery. In the second case, the neonatal serum contained 14 µg/ml of theophylline at delivery, 3 µg/ml higher than the cord or maternal serum concentration. It is possible that the fetus behaves as a pharmacokinetically "deep" compartment with slower drug elimination relative to maternal excretion. Serial serum theophylline concentrations in the neonates were determined at 6, 18, 30, and 40 hours after delivery. For the first 18 hours of life, both neonates' serum contained theophylline within or very close to the therapeutic range (10 to 20 µg/ml) in adults and children. Both neonates reported on in this article had minor clinical symptoms that may have been related to the theophylline present in their serum. Neonates of mothers receiving theophylline products should be monitored for the pharmacologic actions of theophylline.