Distribution of inhaled fluticasone propionate between human lung tissue and serum in vivo.
High retention of inhaled glucocorticoids in the airways means prolonged anti-inflammatory action and low delivery into the serum. The objective of this study was to investigate the retention in and distribution of inhaled fluticasone propionate (FP) between central and peripheral human lung tissue and serum in vivo. In 17 patients undergoing lung resection surgery, a single 1.0 mg dose of FP was inhaled at varying time-points (range 2.8-21.7 h) preoperatively. Peripheral and central lung tissue was obtained, and blood was drawn simultaneously. FP concentrations in central lung tissue were approximately three to four times higher than peripheral lung tissue concentrations, which in turn, exceeded those found in serum by 10 times. FP was detectable up to 21 and 16 h, respectively, after inhalation, with drug levels falling almost in parallel in peripheral lung tissue and in serum. The results of this study demonstrate that fluticasone propionate is retained in lung tissue for a long time. Serum concentrations after a single inhaled dose are low. Retention of high concentrations of fluticasone propionate in the airways may promote high topical anti-inflammatory activity.
Esmailpour
N
N
Institut für Pharmazeutische Chemie, Westfälische Wilhelms-Universität Münster, Germany.
Högger
P
P
Rabe
K F
KF
Heitmann
U
U
Nakashima
M
M
Rohdewald
P
P
D000280:Administration, Inhalation; D000287:Administration, Topical; D000730:Androstadienes / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D005260:Female; D000068298:Fluticasone; D005938:Glucocorticoids; D006801:Humans; D008168:Lung / Q000378:metabolism*; D008175:Lung Neoplasms / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D013997:Time Factors
D000730:Androstadienes; D000893:Anti-Inflammatory Agents; D005938:Glucocorticoids; D000068298:Fluticasone