Therapeutic ratio of hydrofluoroalkane and chlorofluorocarbon formulations of fluticasone propionate.
OBJECTIVE
To compare the therapeutic ratio of chlorofluorocarbon (CFC) and hydrofluoroalkane-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 micro g/d and 1,000 microg/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 micro g (19.2 micro g) completed the study. All treatments significantly improved PD20 values and morning peak expiratory flow vs placebo, while 1,000 microg/d was significantly better than 500 microg/d for the CFC formulation of FP (CFC-FP) but not the HFA formulation of FP (HFA-FP). Only 1,000 microg/d of CFC-FP caused significant suppression of overnight urinary cortisol/creatinine compared to placebo. There were no differences between formulations at either dose.


CONCLUSIONS
The increased airway benefit with CFC-FP > 500 microg/d was offset by greater systemic effects. Although HFA-FP had fewer systemic effects than CFC-FP at 1,000 microg/d, there was no benefit to increasing HFA-FP to > 500 microg/d.
Fowler
Stephen J
SJ
Asthma and Allergy Research Group, Department of Clinical Pharmacology and Therapeutics, Ninewells Hospital and Medical School, University of Dundee, Dundee, UK.
Orr
Linda C
LC
Sims
Erika J
EJ
Wilson
Andrew M
AM
Currie
Graeme P
GP
McFarlane
Lesley
L
Lipworth
Brian J
BJ
D000280:Administration, Inhalation; D000287:Administration, Topical; D000328:Adult; D000335:Aerosol Propellants; D000730:Androstadienes / Q000008:administration & dosage / Q000737:chemistry* / Q000627:therapeutic use*; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000737:chemistry* / Q000627:therapeutic use*; D001249:Asthma / Q000188:drug therapy*; D017402:Chlorofluorocarbons / Q000008:administration & dosage; D018592:Cross-Over Studies; D005260:Female; D000068298:Fluticasone; D005938:Glucocorticoids; D006801:Humans; D006845:Hydrocarbons, Fluorinated / Q000008:administration & dosage; D008297:Male; D016037:Single-Blind Method; D005466:Fluorocarbons
D000335:Aerosol Propellants; D000730:Androstadienes; D000893:Anti-Inflammatory Agents; D017402:Chlorofluorocarbons; D000068298:Fluticasone; D005938:Glucocorticoids; D006845:Hydrocarbons, Fluorinated; C094049:apaflurane; D005466:Fluorocarbons