Effects of food on the absorption of theophylline in children

Abstract

The results of studies evaluating the effects of a standardized substantial breakfast on the absorption of four different sustained-release theophylline preparations in children and adults are summarized. Theolair SR showed a substantial reduction in rate but not extent of absorption. With Theo-Dur Sprinkle the bioavailability was reduced to 44%, and the absorption profiles became unpredictable with marked interindividual variations. Apart from a minor shift to the right of the serum concentration versus time curve no clinically important food effect was found when Somophyllin was tested. Pronounced “dose dumping” and increases in maximum serum concentration were observed in half the patients when Uniphyllin was taken with food, whereas bioavailability and time to maximum serum concentration remained unchanged. The food effect was more marked in children than in adults with all preparations, and some of the effects were found in children only, indicating that it is not sufficient to examine the influence of food solely in adults. It is concluded that the in vivo performance of sustained-release theophylline formulations in combination with food cannot be predicted on the results from absorption studies in fasting patients or from in vitro dissolution tests. Furthermore, individual data are often more important than mean data, which may sometimes even be misleading.