Brindley C, Falcoz C, Mackie A E, Bye A
Drug Metabolism and Pharmacokinetics, Quintiles Scotland Limited, Edinburgh.
Clin Pharmacokinet. 2000;39 Suppl 1:1-8. doi: 10.2165/00003088-200039001-00001.
The aim of this analysis was to assess the rate and extent of systemic availability of inhaled fluticasone propionate (FP) from 2 dry powder systems (Diskhaler and Diskus) and a metered-dose inhaler (MDI) by deconvolution analysis.
The inhalation devices were evaluated in 3 separate studies with identical protocols. 12 healthy male volunteers were randomised to receive FP given as a 1000 microg inhaled dose and 250 microg by intravenous infusion according to a double-blind double-dummy crossover design. The bioavailability of FP after inhalation represents absorption of the drug from the lungs, since the bioavailability of the swallowed portion of the inhaled dose is negligible.
When corrected for the bioavailability (of FP) achieved by each inhalation device, the rate of absorption of FP over the first 2 hours was rapid from all devices. The mean time for absorption of 50% of the bioavailable dose was 1.6, 2.4, and 2.2 hours for the Diskhaler, Diskus and MDI, respectively. Thereafter, absorption from each device was prolonged, with approximately 10% of the dose remaining in the lungs 12 hours after inhalation.
Irrespective of the inhalation device used, the prolonged absorption of FP into the systemic circulation indicates a long residence time in the lungs.
本分析旨在通过反卷积分析评估两种干粉吸入系统（都保和准纳器）及一种定量吸入气雾剂（MDI）中吸入丙酸氟替卡松（FP）的全身可用性速率和程度。
在3项方案相同的独立研究中对吸入装置进行评估。12名健康男性志愿者按照双盲双模拟交叉设计随机接受1000微克吸入剂量的FP以及250微克静脉输注的FP。吸入后FP的生物利用度代表药物从肺部的吸收，因为吸入剂量中吞咽部分的生物利用度可忽略不计。
校正每种吸入装置所达到的（FP）生物利用度后，所有装置在最初2小时内FP的吸收速率都很快。都保、准纳器和MDI吸收50%生物可利用剂量的平均时间分别为1.6小时、2.4小时和2.2小时。此后，每种装置的吸收都延长，吸入12小时后约10%的剂量仍留在肺部。
无论使用何种吸入装置，FP向体循环的吸收延长表明其在肺部的停留时间较长。
