[Delayed-action theophylline versus placebo on the ventilatory function of stable asthmatic patients. Study in...

The aim of this study was to measure the results of a long-acting theophylline (Planphylline) on the flow rates of stable asthmatic patients while taking into account the spontaneous circadian variations of the ventilatory function. 27 patients were involved in this randomized, double-blind, cross-over trial; they received 10 mg/kg/day in two doses at 8.30 a.m. and 8.30 p.m or the placebo. The product was administered over two 4-day periods separated by a 3-day wash-out period. The theophylline concentration and bronchial flows (FEV1; MMEFR 25-75) were measured at 8 a.m., 10.30 a.m., noon, and 3 p.m. on days 1 and 4 of each period; 11 patients measured their hourly PEFR from 8 a.m to 10 p.m those same days. The results can be analysed for 19 patients, including the 11 who measured their PEFR. The first day of treatment (D1), the theophylline concentration rose regularly without going above 10 micrograms/ml. On the fourth day of treatment (D4), the mean maximum concentration was above 10 micrograms/ml and the 8 a.m rate was superior to 8 micrograms/ml for 14 patients out of 19. The bronchodilating effect of Planphylline is significant for all bronchial flow rates (FEV1 less than 0.01; MMEFR 25-75 less than 0.05; PEFR less than 0.01, n = 11). On D1, the FEV1 becomes normal. On D4, the MMEFR 25-75 is still only partially improved, in spite of the theophylline concentration obtained. Because of the spontaneous diurnal improvement of bronchial rates, only the 8 a.m, 10.30 a.m. and 3 p.m. FEV1 obtained with Planphylline are statistically different from those obtained with placebo.(ABSTRACT TRUNCATED AT 250 WORDS)