Advair Diskus - Clinical Pharmacology

(Page 3)

One (1) inhalation twice daily of the following treatments was administered:

ADVAIR DISKUS 500/50, fluticasone propionate powder 500 mcg and salmeterol powder 50 mcg given concurrently, or fluticasone propionate powder 500 mcg alone. Mean peak steady-state plasma concentrations of fluticasone propionate averaged 57, 73, and 70 pg/mL, respectively, indicating no significant changes in systemic exposure of fluticasone propionate. No plasma concentrations of salmeterol were measured in this repeat-dose study. No significant changes in excretion of fluticasone propionate or salmeterol were observed.

The terminal half-life of fluticasone propionate averaged 5.33 to 7.65 hours when ADVAIR DISKUS was administered, which is similar to that reported when fluticasone propionate was given concurrently with salmeterol or when fluticasone propionate was given alone (average, 5.30 to 6.91 hours). No terminal half-life of salmeterol was reported upon administration of ADVAIR DISKUS or salmeterol given concurrently with fluticasone propionate.

Special Populations:

Formal pharmacokinetic studies using ADVAIR DISKUS have not been conducted to examine gender differences or in special populations, such as elderly patients or patients with hepatic or renal impairment.

Drug Interactions:

In the repeat-and single-dose studies, there was no evidence of significant drug interaction in systemic exposure between fluticasone propionate and salmeterol when given as ADVAIR DISKUS.

Fluticasone Propionate:

Absorption:

Fluticasone propionate acts locally in the lung; therefore, plasma levels do not predict therapeutic effect. Studies using oral dosing of labeled and unlabeled drug have demonstrated that the oral systemic bioavailability of fluticasone propionate is negligible (<1%), primarily due to incomplete absorption and presystemic metabolism in the gut and liver. In contrast, the majority of the fluticasone propionate delivered to the lung is systemically absorbed. The systemic bioavailability of fluticasone propionate from the DISKUS device in healthy volunteers averages 18%. Peak steady-state fluticasone propionate plasma concentrations in adult patients with asthma (N = 11) ranged from undetectable to 266 pg/mL after a 500-mcg twice-daily dose of fluticasone propionate inhalation powder using the DISKUS device. The mean fluticasone propionate