CHRONOTHERAPY OF ASTHMA WITH INHALED STEROIDS - THE EFFECT OF DOSAGE TIMING ON DRUG EFFICACY

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 ben eficial and systemic effects of 800 mu g of inhaled triamcinolone once daily at 3:00 PM (QD group) versus 200 mu g conventional four times a day dosing (QID group). Methods: Efficacy outcome measures included f orced expiratory volume in I second (FEV(1)), peak expiratory pow rate s, bronchial responsiveness, and use of beta-agonist. Systemic effects were blood eosinophil and cortisol levels, 24-hour urinary cortisol, and evaluation for oral candidiasis and dysphonia. Results: The baseli ne 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) incr eased similarly in the QD group to 77% +/- 4% and in the QID group to 74% +/- 4% of predicted value. Likewise, the improvement in morning an d evening peak expiratory flow rates was nor significantly different b etween the groups. Both QD and QID groups experienced comparable daily decrements in beta-agonist use. The systemic responses to the two reg imens as assessed by eosinophil count, morning serum cortisol, and 24- hour urinary cortisol were also comparable. Conclusions: The single da ily administration of inhaled triamcinolone at 3:00 PM has no increase d systemic effects and produces similar improvement in efficacy variab les. A dosing strategy based on once daily dosing should increase comp liance of inhaled steroid use in the clinical setting.