The pharmacokinetics and efficacy of slow-release theophylline with asymmetric dosing in asthmatic Chinese.

Fifteen Chinese subjects with stable asthma were given asymmetric doses of slow-release choline theophyllinate (Theobret) according to body weight; patients under 60 kg (132 lb) received 180 mg at 9 AM and 360 mg at 9 PM for six days (period 1), followed by 180 mg at 1 PM and 360 mg at 9 PM for six days (period 2); for those over 60 kg, the regimen was the same, except that they received 270 mg during the daytime and 540 mg at night. At the end of each period of treatment, concentration of theophylline was measured over 24 hours. Five patients experienced side effects, and two of these were withdrawn from the study. In the remaining 13 patients, optimal concentrations of the drug were attained during most of the 24 hours, and there were only minor pharmacokinetic differences between the two periods of treatment. Compared with observations before treatment, the total symptom score was unchanged, but the peak expiratory flow rate in the morning and evening improved, and the use of inhaled bronchodilator drugs decreased significantly. There was a trend towards progressive improvement as the duration of treatment increased, suggesting that the therapeutic effect of theophylline may lag behind the attainment of optimal concentrations. We conclude that asymmetric dosing regimens of slow-release theophylline are effective and rational in maintenance therapy for asthma and that lower total daily dosages may be more appropriate in Chinese patients when compared to those recommended for white subjects.