Chronotherapy of asthma with inhaled steroids: The effect of dosage timing on drug efficacy☆☆☆★★★

Abstract 

Background: Studies in asthma with systemic corticosteroids given at 3:00 PM have shown a superior therapeutic benefit compared with dosing at other time points. Objective: The study was designed to compare beneficial and systemic effects of 800 μg of inhaled triamcinolone once daily at 3:00 PM (QD group) versus 200 μg conventional four times a day dosing (QID group). Methods: Efficacy outcome measures included forced expiratory volume in 1 second (FEV ₁), peak expiratory flow rates, bronchial responsiveness, and use of β-agonist. Systemic effects were blood eosinophil and cortisol levels, 24-hour urinary cortisol, and evaluation for oral candidiasis and dysphonia. Results: The baseline FEV ₁ was comparable in the two groups: QD = 67% ± 2% and QID = 66% ± 2% of predicted value. After 4 weeks of treatment, FEV ₁ increased similarly in the QD group to 77% ± 4% and in the QID group to 74% ± 4% of predicted value. Likewise, the improvement in morning and evening peak expiratory flow rates was not significantly different between the groups. Both QD and QID groups experienced comparable daily decrements in β-agonist use. The systemic responses to the two regimens as assessed by eosinophil count, morning serum cortisol, and 24-hour urinary cortisol were also comparable. Conclusions: The single daily administration of inhaled triamcinolone at 3:00 PM has no increased systemic effects and produces similar improvement in efficacy variables. A dosing strategy based on once daily dosing should increase compliance of inhaled steroid use in the clinical setting. (J ALLERGY CLIN IMMUNOL 1995;95:1172-8.)

Keywords:  Asthma, inhaled steroids, chronotherapy, dose timing, triamcinolone acetonide

Abbreviations:  BID , Twice daily, FEV ₁ , Forced expiratory volume in 1 second, IQR , Interquartile range, PC ₂₀ , Provocative concentration (of methacholine) causing a 20% fall in FEV ₁, PERF , Peak expiratory flow rate, QD , Once daily, QID , Four times daily, TEC , Total eosinophil count