title: Relationship of formulation and dosing interval to fluctuation of serum theophylline concentration in children with chronic asthma.
abstract: 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.
mesh_terms: D000293:Adolescent; D000328:Adult; D001249:Asthma / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism; D002648:Child; D003692:Delayed-Action Preparations; D005260:Female; D006207:Half-Life; D006801:Humans; D008297:Male; D013607:Tablets; D013806:Theophylline / Q000008:administration & dosage* / Q000097:blood / Q000378:metabolism / Q000627:therapeutic use
chemical_list: D003692:Delayed-Action Preparations; D013607:Tablets; D013806:Theophylline