Theophylline plasma levels and profiles were evaluated in patients with chronic obstructive pulmonary disease during once-daily dosing of an ultrasustained-release theophylline preparation (Theo-1; capsules filled with microgranules containing 400 mg anhydrous theophylline). In a first study, 6 patients received a single morning dose of 800 mg (a) in the fasting state, and (b) with a protein-fat-rich breakfast in a random order, and the systemic theophylline availability was evaluated for 48 h. No significant differences were found either in Cmax (a: 7.0 +/- 3.2 micrograms/ml; b: 7.6 +/- 2.6 micrograms/ml), or in Tmax (a: 11.7 +/- 6.1 h; b: 10.2 +/- 3.6 h). Elimination half-life was in a 11.4 +/- 4.4 h and in b 12.9 +/- 4.8 h (p less than 0.05). In a second study, the steady-state theophylline levels were measured during a 24-hour dosage interval on day 8 after intake of 800 mg at 8 a.m. in 16 patients and at 8 p.m. in 11 patients. Plateau-shaped plasma concentration-time curves were obtained, with small fluctuations between the peak (Cmax) and trough (Cmin) levels: [100(Cmax-Cmin)/Cmin] was 83 +/- 40% after morning dose, and 54 +/- 26% after evening dose (p less than 0.05). Cmax was 12 +/- 5 and 11 +/- 4 micrograms/ml, respectively (NS). Tmax was 9 +/- 3 and 11 +/- 3 h, respectively (NS). The FDA fluctuation for the 37 patients was 48 +/- 20%. In a third study, the dose-plasma concentration relationship was evaluated in steady state in 6 patients receiving 400, 800 and 1,200 mg for 3 days each. The trough plasma concentrations were 2.6 +/- 0.9, 6.2 +/- 2.1 and 10.2 +/- 3.1 micrograms/ml, respectively. Six hours after drug intake the plasma levels were 5.0 +/- 1.6, 10.6 +/- 2.5 and 15.4 +/- 4.2 micrograms/ml, respectively; and 12 h after drug intake, 4.9 +/- 1.4, 11.6 +/- 2.4 and 14.5 +/- 3.7 micrograms/ml, respectively. In conclusion, we found in these studies that with once-daily dosing of the ultrasustained-release preparation Theo-1, plateau-shaped 24-hour theophylline plasma levels could be achieved. The relationship between daily dosage and theophylline plasma levels was linear intraindividually but showed an important interindividual variation. No consistent interference by food intake was found and no serious side effects occurred within therapeutic plasma levels.