Therapeutic ratio of hydrofluoroalkane and chlorofluorocarbon formulations of fluticasone propionate

Objectives: To compare the therapeutic ratio of chlorofluorocarbon (CFC) and hydrofluoro-alkane-134a (HFA) formulations of fluticasone propionate (FP). Methods: We performed a randomized, placebo-controlled, crossover study comparing 6 weeks of treatment with FP using 500 mug/d and 1,000 mug/d formulations of CFC and HFA. The primary end points were provocative dose of methacholine causing a 20% fall in FEV1 (PD20) and overnight urinary cortisol/creatinine excretion. Results: Eighteen patients with mild-to-moderate asthma and geometric mean (SEM) PD20 of 82.3 mug (19.2 mug) completed the study. All treatments significantly improved PD20 values and morning peak expiratory flow vs placebo, while 1,000 mug/d was significantly better than 500 mug/d for the CFC formulation of FP (CFC-FP) but not the HFA formulation of FP (HFA-FP). Only, 1,000 mug/d of CFC-FP caused significant suppression of overnight urinary cortisol/creatinine compared to placebo. There were no differences between formulations at dither dose. Conclusions: The increased airway benefit with CFC-FP > 500 mug/d was offset by greater systemic effects. Although HFA-FP had fewer systemic effects than CFC-FP at 1,000 mug/d, there. was no benefit to increasing HFA-FP to > 500 mug/d.