Bioavailability of fluticasone propionate and mometasone furoate aqueous nasal sprays
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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.
Twelve healthy subjects completed this three-way, cross-over study. They received FPANS (50 μg/spray), MFANS (50 μg/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.
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.
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.
KeywordsFluticasone propionate Mometasone furoate Nasal bioavailability
- 1.Dolovich J, O’Connor M, Stepner N, Smith A, Sharma RK (1994) Double-blind comparison of intranasal fluticasone propionate, 200 micrograms, once daily with 200 micrograms twice daily in the treatment of patients with severe seasonal allergic rhinitis to ragweed. Ann Allergy 72:435–440PubMedGoogle Scholar
- 6.McDowell JE, Mackie AE, Ventresca GP, Bye A (1997) Pharmacokinetics and bioavailability of intranasal fluticasone in humans. Clin Drug Invest 1:44–52Google Scholar
- 7.Schering-Plough Research Institute (1998) SCH 32088: single dose absolute bioavailability study of mometasone nasal spray in volunteers with evidence of allergic rhinitis. Study No. C93–196 (data on file)Google Scholar
- 8.Callejas S, Biddlecombe R, Jones A, Joyce K, Pereira A, Pleasance S (1998) Determination of the glucocorticoid fluticasone propionate in plasma by automated solid-phase extraction and liquid chromatography-tandem mass spectrometry. J Chromatogr 718:243–250Google Scholar
- 9.FDA Summary Basis of Approval (2000) NDA 20762, Nasonex Nasal Spray Medical Officer ReviewGoogle Scholar
- 10.Price AC, Daley-Yates PT, Wright AM, Callejas S (2000) Negligible absolute bioavailability and no HPA-axis effects after multiple 200 µg daily doses of Fluticasone propionate (FP) administered from the aqueous nasal spray (FPANS). Eur Resp J 16:279sGoogle Scholar
- 17.Brannan MD, Seiberling M, Cutler DL (1996) Lack of systemic activity with intranasal mometasone furoate. J Allergy Clin Immunol 97:198Google Scholar
- 18.Brannan MD, Herron JM, Reidenberg P (1996) Lack of HPA axis suppression following 36 days of intranasal mometasone furoate. Ann Allergy Asthma Immunol 78:154Google Scholar
- 20.Daley-Yates PT, Richards DH (2001) Pharmacokinetic and pharmacodynamic relationships for intranasal corticosteroids (INCS). J Allergy Clin Immunol 107:S313Google Scholar