Bioavailability of fluticasone propionate and mometasone furoate aqueous nasal sprays.
OBJECTIVE
To compare the systemic exposure for intranasal mometasone furoate (MF) and fluticasone propionate (FP) aqueous nasal sprays (ANS) in terms of serum and urinary cortisol parameters and plasma pharmacokinetics.


METHODS
Twelve healthy subjects completed this three-way, cross-over study. They received FPANS (50 microg/spray), MFANS (50 microg/spray) or placebo ANS, eight sprays per nostril every 8 h for 4 days. Cortisol measurements were made at baseline and day 4. FP and MF plasma concentrations were also measured on day 4.


RESULTS
MFANS produced similar mean plasma AUC (123 pmol/l h) to FPANS (112 pmol/l h). Despite the use of high doses, necessary to generate adequate pharmacokinetic data, only minor reductions in cortisol parameters were found, with no difference between FPANS and MFANS.


CONCLUSIONS
FP and MF have similar and very low systemic bioavailability when administered intranasally using a high-dose regimen. It is therefore unlikely that therapeutic doses of intranasal FP or MF will produce dissimilar or significant degrees of systemic exposure or systemic effects.
Daley-Yates
P T
PT
GlaxoSmithKline Research and Development, Clinical Pharmacology and Discovery Medicine, Greenford Road, UB6 0HE Greenford, Middlesex, UK. Peter.T.Daley-Yates@gsk.com
Kunka
R L
RL
Yin
Y
Y
Andrews
S M
SM
Callejas
S
S
Ng
C
C
D000281:Administration, Intranasal; D000305:Adrenal Cortex Hormones / Q000008:administration & dosage / Q000493:pharmacokinetics*; D000328:Adult; D000336:Aerosols; D000730:Androstadienes / Q000008:administration & dosage / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001682:Biological Availability; D018592:Cross-Over Studies; D005260:Female; D000068298:Fluticasone; D006801:Humans; D006854:Hydrocortisone / Q000097:blood / Q000652:urine; D008297:Male; D000068656:Mometasone Furoate; D011244:Pregnadienediols / Q000008:administration & dosage / Q000493:pharmacokinetics*
D000305:Adrenal Cortex Hormones; D000336:Aerosols; D000730:Androstadienes; D011244:Pregnadienediols; D000068656:Mometasone Furoate; D000068298:Fluticasone; D006854:Hydrocortisone