| Abstrakt: |
Using a double-blind, placebo-control, crossover study design, 8 asthmatic children (8––15 years) were evaluated for temporal patterns in airways function throughout separate study periods when treatment was placebo or Theo-24®® once-daily on separate occasions at 0600, 1500 or 2100 hr. During 39-hr in-hospital observations, pulmonary function and serum theophylline concentrations (STC) were assessed every 3 hr under all treatments. The pharmacokinetics of Theo-24®® varied greatly depending on the dosing time. For the afternoon and evening dosings, the CmaxTmax, AUC1%swing,%fluctuation,%AUC fluctuation,%nocturnal excess and Cav(2,6hr)were all statistically significantly greater than for the morning dosing. Compared with the placebo regimen, dosing patients with Theo-24®® at 1500 hr disrupted circadian patterns of airways function, especially airways patency, while dosing at 2100 hr, reduced the amplitude and shifted the acrophase of several spirometric measures to a slightly earlier time. Theo-24®® treatment irrespective of dosing time resulted in comparable enhancement of the group24-hr mean, minimum and maximum values of airways patency with reference to placebo baselines. Theo-24®® dosing at 1500 or 2100 hr, however, resulted in the best effect on the airways as assessed by the 24-hr mean FEV1.0level in 7 of the 8 asthmatic children. When the drug was given at 1500 hr, the time of lowest FEV1.0was shifted from the nighttime hours in 5 of 8 patients. These Findings suggest that clinicians need to individualize the theophylline dosing schedule of patients to best control the symptoms of asthma. |
