Comparison of Once-Daily Evening Versus Morning Sustained-Release Theophylline Dosing For Nocturnal Asthma

Abstract

Eight diurnally active (∼0730–1100hr) adults (41–61 yr) suffering from nocturnal asthma volunteered for a double-blind, cross-over randomized study of a once-daily dosing (600–900 mg/24hr) of Armophylline® (Rorer s.a., France), a sustained-release theophylline given either at 0800 hr or 2000 hr for 8-day durations. Study variables monitored daily were: (a) self-measured peak expiratory flow (PEF), heart rate, oral temperature and self-rated fatigue checked every 2hr during the waking span as well as upon spontaneous nocturnal awakenings and (b) duration and subjective characteristics of sleep rated every morning. In addition, serum theophylline concentration (STC) plus the variables in (a) were sampled every 2hr during the 24 hr of the eighth day of each timed treatment span. Rxat 0800 hr was associated with a nocturnal dip in PEF of 20 ± 2.8% (X± S.E.M.) from the level achieved at the time of the diurnal crest; Rxat 2000 hr moderated the nocturnal fall; it was only 10 ±2.1% and within the physiologic limits of non-asthmatic persons. The STC peak height (Cmax) was greater (p<0.05) and time-to-peak (Tmax) shorter (P< 0.005) with Rxat 0800 hr than at 2000 hr. With Rxat 2000 hr an STC plateau of ∼12 hr resulted. A statistically significant correlation (r=0.86; p<0.01) between PEF and the corresponding-in-time STC was observed with Rxat 2000 hr but not with Rxat 0800 hr. A small, but statistically significant, higher heart rate resulted from 2000 hr dosings in five out of eight subjects relative to the 0800 hr dosing. There were no differences in the sleep characteristics nor in oral temperature between dosing times. Once-daily (600–900 mg) SRT dosing at 2000 hr controlled the nocturnal dip of bronchial patency with no major side-effects in diurnally active adult patients with nocturnal allergic asthma.