Relationship of formulation and dosing interval to fluctuation of serum theophylline concentration in children with chronic asthma.

Completeness of absorption and fluctuations in serum, theophylline concentration were examined in 14 children, 8 to 17 years of age (mean 12.4), with chronic asthma treated in variable sequence with a slow-release formulation at eight- and 12-hour intervals, and plain tablets every six hours. The total fraction absorbed for the slow-release formulation was 0.98 +/- 0.07 (mean +/- SEM) during the eight-hour and 0.99 +/- 0.04 during the 12-hour regimens. Observed fluctuations in serum concentration were closely approximated by predictions determined from absorption of single doses in adult volunteers. Available single-dose absorption data then were used to compare predicted fluctuations in serum concentration among nine formulations (18 brand names) for eight- and 12-hour dosing in an average child and adult (elimination half-lives of 3.7 and 8.2 hours, respectively). Although predicted peak concentrations were less than twice the trough for all products when given at 12-hour intervals to an average nonsmoking adult, only two of the nine formulation (both from the same manufacturer) were likely to maintain predicted fluctuations within the 10 to 20 micrograms/ml therapeutic range during 12-hour dosing intervals in an average child. Most children and those adults with rapid elimination generally will require eight-hour dosing with the other products.