Therapeutic advantage of unequal dosing of theophylline in patients with nocturnal asthma.

Two theophylline treatments were compared in a randomized, multiple-dose, crossover study on 20 patients present with nonallergic bronchial asthma. Both products (E = Euphyllin CR, A = Afonilum Retard) were capsules containing micropellets. They were administered according to the recommendations of the manufactures and differed in the total daily theophylline dose (642 mg versus 500 mg), the partition of this dose (1/3 in the morning and 2/3 in the evening versus equal amounts in the morning and evening) and the timing of the evening dose (2200 hr versus 2000 hr). The patients were off oral theophyllines at least 2 days prior to study onset and no other drugs were allowed to be administered during the testing periods. On the 4th day of each study period, serum theophylline concentrations (STC) and peak expiratory flow rate (PEF) were determined every 2 hr. Compared with the 24-hr PEF reference profile taken prior to study onset, both theophylline treatments produced a significantly higher 24-hr PEF average (mesor). Treatment E resulted in significantly higher mesor than A; in addition, the PEF amplitude relative to the mesor was reduced by treatment E when compared with placebo.