ADVAIR DISKUS ADVAIR - GlaxoSmithKline

DETAILED PHARMACOLOGY
Note: For complete information on the pharmacology of the individual compounds
salmeterol xinafoate and fluticasone propionate, please refer to the SEREVENT ® and
FLOVENT ® Product Monographs.
Animals
A safety pharmacology study was performed to determine the potential interaction of
subcutaneously administered fluticasone propionate with the cardiovascular and
respiratory effects of intravenously administered salmeterol xinafoate in anaesthetised
guinea-pigs. Fluticasone propionate (10 mg/kg, sc) or vehicle control was administered
as two doses at 24 hours and 3 hours prior to dosing with salmeterol xinafoate.
Salmeterol at intravenous doses of 0.01 – 100 mcg/kg (including and exceeding those
required for pharmacological effects or amounts likely to be absorbed clinically after
inhalation), had no effects other than those consistent with the known pharmacological
profile of the compound (decreases in blood pressure and increases in heart rate). These
effects were not exacerbated by pre-treatment with fluticasone propionate.
Pharmacokinetics
Plasma concentrations of salmeterol xinafoate and fluticasone propionate administered
concomitantly were determined in single dose inhalation studies in the rat and dog.
Plasma levels at the lowest dose levels used in the studies (28/73 mcg/kg in the rat, and
48/50 mcg/animal in the dog) were about 30-fold and 26-fold greater in rat and 13-fold
and 3- to 5-fold greater in dog than the peak levels likely to occur in man for salmeterol
xinafoate and fluticasone propionate.
Repeat dose pharmacokinetics of salmeterol xinafoate and fluticasone propionate has
been obtained by monitoring plasma concentrations in inhalation toxicity studies in the
rat and dog.
In both species, plasma levels of fluticasone propionate were not affected by salmeterol
administered concurrently and plasma levels of salmeterol were not affected by coadministration
with fluticasone propionate.
Human
The pharmacodynamic effects and pharmacokinetics of the combination product in the
DISKUS ® powder inhaler were investigated in healthy adult male and female volunteers
after single and repeat-dose administration.
Those studies showed that the systemic pharmacodynamic effects of salmeterol xinafoate
and fluticasone propionate are essentially unchanged when the two drugs are
administered in combination, when compared with the component drugs given alone or
concurrently.
July 29, 2014
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