Systemic exposure and urinary cortisol effects of fluticasone propionate formulated with hydrofluoroalkane in 4- to 11-year-olds with asthma.
The systemic exposure of fluticasone propionate with hydrofluoroalkane propellant compared with chlorofluoro-carbon propellant and the effect of fluticasone propionate hydrofluoroalkane on 24-hour urinary cortisol in children aged 4 to 11 years with asthma were evaluated. Study 1 was an open-label, 2-way crossover study in which 16 subjects were randomized to 7.5 days each of fluticasone propionate hydrofluoroalkane 88 mug twice a day or fluticasone propionate chlorofluorocarbon 88 mug twice a day. In study 2, 63 subjects received 13.5 days of placebo followed by 27.5 days of fluticasone propionate hydrofluoroalkane 88 mug twice a day. The main outcome measure for study 1 was the difference between fluticasone propionate hydrofluoroalkane and fluticasone propionate chlorofluorocarbon in fluticasone propionate AUC(last) (area under the plasma fluticasone propionate concentration-time curve from zero up to the last quantifiable plasma concentration), and for study 2, 24-hour overnight urinary cortisol excretion. In study 1, fluticasone propionate systemic exposure was significantly lower (55%) with hydrofluoroalkane metered dose inhaler compared with chlorofluorocarbon metered dose inhaler. Study 2 showed no statistically significant changes in 24-hour overnight urinary cortisol excretion and no relationship to fluticasone propionate systemic exposure at this dose. The results of these 2 studies showed that in children aged 4 to 11 years with asthma, fluticasone propionate hydrofluoroalkane has lower systemic exposure compared with chlorofluorocarbon and no hypothalamic-pituitary-adrenal axis effects as measured by 24-hour urinary cortisol excretion.
Kim
Kenneth T
KT
West Coast Clinical Trials, LLC, 5630 Cerritos Ave, Cypress, CA 90630, USA.
Milgrom
Henry
H
Yoon
Y Kellie
YK
Levy
Arden L
AL
Matz
Paul
P
Welch
Michael J
MJ
Cahn
Anthony
A
Collins
David A
DA
Kathman
Steven
S
Mehta
Rashmi
R
Su
Sheng-Fang
SF
Kunka
Robert L
RL
D000280:Administration, Inhalation; D000335:Aerosol Propellants / Q000737:chemistry; D000730:Androstadienes / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use*; D018927:Anti-Asthmatic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000737:chemistry; D019540:Area Under Curve; D001249:Asthma / Q000188:drug therapy* / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D017402:Chlorofluorocarbons / Q000737:chemistry; D003371:Cough / Q000139:chemically induced; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D005334:Fever / Q000139:chemically induced; D000068298:Fluticasone; D006207:Half-Life; D006261:Headache / Q000139:chemically induced; D006801:Humans; D006845:Hydrocarbons, Fluorinated / Q000737:chemistry*; D006854:Hydrocortisone / Q000031:analogs & derivatives / Q000652:urine*; D008297:Male; D036501:Metered Dose Inhalers; D009325:Nausea / Q000139:chemically induced; D012141:Respiratory Tract Infections / Q000139:chemically induced; D005466:Fluorocarbons
D000335:Aerosol Propellants; D000730:Androstadienes; D018927:Anti-Asthmatic Agents; D017402:Chlorofluorocarbons; D000068298:Fluticasone; D006845:Hydrocarbons, Fluorinated; D006854:Hydrocortisone; C001380:6 beta-hydroxycortisol; C094049:apaflurane; D005466:Fluorocarbons