Comparison of sustained-release theophylline scheduled conventionally (twice-daily, equal interval in equal amount) versus once-daily mornings or evenings on circadian pattern of bronchial patency in asthmatics.

The effects of differently timed, but equivalent TheoDur (Key Pharmaceutical Co.) dosage schedules--twice-daily equally divided 12 hr (BID), once-daily evening (OD-PM) and once-daily morning (OD-AM)--were compared under steady-state conditions in 10 adult asthmatics with a documented history of nocturnal dyspnea. Assessments of airways function by spirometry were done every 3-hr over one complete 24-hr dosing interval for each dosage schedule under carefully controlled conditions. The different TheoDur regimens did not affect the 24-hr group average FEV1.0, PEF, MMEF or FVC. However, statistically significant circadian variation in airways function existed irrespective of the drug dosing schedule. Airways patency and FVC were least overnight (0200-0500 hr) and best during the morning or afternoon. With regard to FEV1.0 and PEF, which evidenced group circadian change for BID and OD-PM regimen by Cosinor analysis, the peak-to-trough (double amplitude) difference expressed as a percentage of the 24-hr average was rather large, being greatest for the OD-PM schedule (20.5% for FEV1.0 and 24.3% for PEF). The data for the 10 participants revealed individual differences in the effectiveness of the 3 studied theophylline dosing regimens when assessed in terms of the mean level and stability of airways function over the 24 hr. Based on the findings, neither the BID, OD-PM nor the OD-AM regimen effectively moderated the nocturnal deterioration of pulmonary function suggesting theophylline as dosed and timed may not be as efficacious as desired for patients with a history of strictly nighttime dyspnea. Thus, the schedule and prescription of TheoDur must take into account differences between patients, including the time when asthma symptoms are most likely to be experienced by each.