Comparative dose study of a theophylline sustained-release tablet formulation after repeated administrations.

Two different doses of a sustained-release tablet formulation of theophylline were administered to two groups of patients affected by chronic obstructive pulmonary disease. Pharmacokinetic parameters were determined after a single administration of the drug. In this experiment, the theophylline plasma levels were determined 1, 2, 4, 8, 12 and 24 h after the drug administration. In another experiment, the patients received the drug "once-daily", in the morning, for nine consecutive days. Plasma theophylline levels were monitored 24 h after the first administration and twice daily on days 3, 6 and 9. Patients receiving 700 mg/day showed theophylline levels ranging from 8.49 +/- 1.04 micrograms/ml to 20.99 +/- 2.09 micrograms/ml. In this group theophylline concentrations were found to be greater than 10 micrograms/ml also 24 h after the tablets' administration. These data show that in case of single daily theophylline administration an high dosage is necessary to maintain the drug concentration within the range of therapeutic levels.