C. Crim et al., A review of the pharmacology and pharmacokinetics of inhaled fluticasone propionate and mometasone furoate, CLIN THER, 23(9), 2001, pp. 1339-1354
Background: Fluticasone propionate is an established corticosteroid adminis
tered intranasally for the treatment of rhinitis or by oral inhalation for
the treatment of asthma. Mometasone furoate, a closely related corticostero
id currently available in an intranasal formulation, is being investigated
in an oral inhalation formulation for the treatment of asthma.
Objective: This article reviews available data on the comparative structure
-activity relationships, chemistry, pharmacology, pharmacokinetics, and sys
temic bioavailability of fluticasone propionate and mometasone furoate to a
ssess whether claims of differences in the absolute systemic bioavailabilit
y of the 2 compounds are supported by the published literature.
Methods: Information for this review was identified through a MEDLINE searc
h of the literature from 1966 to the present that contained the term mometa
sone or fluticasone. The resulting list was narrowed by excluding articles
dealing with dermatologic applications. A systematic review was conducted o
f the identified literature pertaining to the molecular structure, topical
potency, lipophilicity, pharmacokinetics, and bioavailability of the 2 agen
ts. Additionally, the pharmacology of the 2 moieties was assessed by a revi
ew of the available literature on receptor binding affinity, transactivatio
n and transrepression potency, and inhibition of inflammatory-cell cytokine
expression.
Results: Based on the available data, fluticasone propionate and mometasone
furoate have similar physicochemical properties and structure-activity rel
ationships. When administered intranasally, mometasone furoate is reported
to have comparable relative systemic bioavailability to that of fluticasone
propionate (mean plasma area under the curve, 123 pmol.h/L vs 112 pmol.h/L
, respectively). When administered as a single dose by dry powder inhaler,
orally inhaled fluticasone propionate is reported to have a total systemic
bioavailability of similar to 17%, whereas that of mometasone furoate is re
ported to be <1%. However, the mometasone furoate bioavailability study tha
t reported the latter value used lower drug doses and a less sensitive assa
y than the fluticasone propionate bioavailability study. When multiple-dose
data were used, mometasone furoate had an estimated 11% systemic bioavaila
bility, similar to that of fluticasone propionate.
Conclusions: Inhaled fluticasone propionate and mometasone furoate appear t
o have comparable potential systemic absorption and, based on the total sys
temic bioavailabilities of the parent compounds, have a low potential for s
ystemic side effects at the recommended clinical doses. However, in the cas
e of mometasone furoate, the contribution of the active metabolites to syst
emic effects has not been adequately assessed.