Relationship of Formulation and Dosing Interval to Fluctuation of Serum Theophylline Concentration in Children With Chronic Asthma

Document Type

Article

Publication Date

1-1-1981

Description

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 slowrelease 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 formulations (both from the same manufacturer) were likely to maintain predicted fluctuations within the 10 to 20 μg/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.

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