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Systemic Exposure and Urinary Cortisol Effects of Fluticasone Propionate Formulated With Hydrofluoroalkane in 4‐ to 11‐Year‐Olds With Asthma
Author(s) -
Kim Kennet T.,
Milgrom Henry,
Yoon Y. Kellie,
Levy Arde L.,
Matz Paul,
Welch Michae J.,
Cahn Anthony,
Collins Davi A.,
Kathman Steven,
Mehta Rashmi,
Su ShengFang,
Kunka Rober L.
Publication year - 2008
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1177/0091270007309704
Subject(s) - fluticasone propionate , chlorofluorocarbon , fluticasone , metered dose inhaler , inhaler , medicine , excretion , chemistry , endocrinology , corticosteroid , asthma , organic chemistry
The systemic exposure of fluticasone propionate with hydrofluoroalkane propellant compared with chlorofluorocarbon 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 μg twice a day or fluticasone propionate chlorofluorocarbon 88 μg twice a day. In study 2, 63 subjects received 13.5 days of placebo followed by 27.5 days of fluticasone propionate hydrofluoroalkane 88 μg 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.