Retention of Flunisolide in Rat Lungs after Single Inhalation

[摘要] Flunisolide (6α-fluorine 11β, 16α, 17α, 21-tetrahydroxypregna-1, 4-diene-3.20-dione 16.17 acetonide) is a potent inhaled corticosteroid, as demonstrated by its anti-inflammatory activities. Clinical data have widely demonstrated that inhaled flunisolide administered twice daily is effective for the treatment of bronchial asthma. However, pharmacokinetic studies suggest that the high solubility rate of flunisolde in bronchial fluid reduces the residence time of the drug in the lungs to a few minutes. The aim of this study is to determine the concentration of flunisolide in lung tissue of rats after administration by inhalation at varying time periods. Male Wistar rats weighing approximately 300 g were divided into four groups and administered a single dose of 1 mg flunisolide via inhalation. Rats were sacrificed with the exposure to CO2 either immediately or 3,6,12 hours after inhalation. The whole lung was then surgically removed and analysed for flunisolide concentration using gas chromatography. The mean concentration (2 standard deviation) of flunisolide detected in the lung tissue at 0, 3, 6 hours after inhalation were 66.4 (11.9), 48.6 (5.9), 42.7 (8.1) ng/mg of proteins, respectively. No flunisolide was detected after 12 hours in lung tissue. We conclude that flunisolide is retained for long duration (more than 6 hours) in lung tissue. This finding partially explains the mechanisms of action of the drug.

[发布日期] 2012-01-01

[关键词] flunisolide;gas chromatography;lung;rat