Plasma xanthine levels in low birthweight infants treated or not treated with theophylline

The use of theophylline in the management of apnoea in the newborn was studied in 33 preterm infants. Infants received a dose of 3 mg/kg, 13 of them every six hours, the remaining 20 every eight hours. All the infants had significantly fewer apnoeic episodes. In a pharmacokinetic study, the half life of theophylline was 30.3 +/- 7.2 hours and the clearance rate was 23.9 +/- 5.06 ml/kg per hour (means and SD). The plasma theophylline level remained constant at between 13 and 15 mg/l from the 5th day of treatment but, at the same time, the plasma levels of caffeine rose to a mean level of 4.4 mg/l. Caffeine was detectable in plasma at birth, and in preterm infants not receiving theophylline; plasma levels of caffeine tended to be similar to the levels in their mothers' milk. These observations have led to clear conclusions on the optimum timing and dosage of theophylline, and on the need to monitor plasma levels of both theophylline and caffeine in newborn infants treated with theophylline.