[Time-related distribution of delayed-action theophylline in the treatment of chronic obstructive bronchopneumopathies].

Three regimens of sustained-release theophylline (Theostat) were administered to 12 male patients with chronic obstructive lung disease in randomized cross over trial. Each 7 days' treatment consisted of: treatment A: 8 mg/kg/day at 07.00 h and 4 mg/kg/day at 19.00 h; treatment B: 6 mg/kg/day at 07.00 h and 6 mg/kg/day at 19.00 h; treatment C: 4 mg/kg/day at 07.00 h and 8 mg/kg/day at 19.00 h. Peak expiratory flow was recorded each day at 07.00, 11.00, 15.00, 19.00 and 23.00 hours, and theophylline plasma levels were determined on the 7th day of each treatment sequence. Cosinor analysis of the data revealed significant circadian rhythms of 24 hr mean Peak expiratory flow for each treatment: the mesor was significantly higher with C and acrophases were located at 14.26 for A, 14.25 for C; a phase shift of the acrophase was detected for B (09.58). These data suggest that an unequal twice daily sustained-release theophylline dosing with higher dose in the evening may be beneficial in the treatment of chronic obstructive lung disease.