Mackie A E, McDowall J E, Ventresca P, Bye A, Falcoz C, Daley-Yates P T
Lilly Research Centre, Windlesham, Surrey, England.
Clin Pharmacokinet. 2000;39 Suppl 1:17-22. doi: 10.2165/00003088-200039001-00003.
The pharmacokinetic profile of a single dose of inhaled fluticasone propionate (FP) administered via a metered-dose inhaler (MDI), containing either a chlorofluorocarbon (CFC) or hydrofluoroalkane (HFA) propellant was investigated in healthy volunteers.
Two randomised, double-blind, crossover studies were conducted, each in 12 male volunteers. Both studies compared pharmacokinetic data after a single inhaled dose of FP 1000 microg from a MDI containing either CFC (CFC MDI) or HFA (HFA MDI) with a single intravenous dose of FP 250 microg.
The maximum plasma FP concentrations after inhalation via the 2 types of MDI were almost identical (0.56 and 0.54 microg/L for CFC MDI and HFA MDI, respectively); bioavailability values of inhaled FP from the 2 MDIs were also similar (geometric mean values: 26.4% via the CFC MDI and 28.6% via the HFA MDI). Inhalation of FP via both MDI formulations produced similar reductions in urinary cortisol excretion over 12 and 24 hours postdose.
The bioavailability values of FP after inhalation via a CFC MDI and an HFA MDI are similar. The 2 formulations deliver comparable amounts of FP, and systemic exposures to FP from the 2 devices, measured by urinary cortisol excretion, are not significantly different.
在健康志愿者中研究通过含有氯氟烃(CFC)或氢氟烷烃(HFA)推进剂的定量吸入器(MDI)单次吸入丙酸氟替卡松(FP)后的药代动力学特征。
进行了两项随机、双盲、交叉研究,每项研究有12名男性志愿者。两项研究均比较了从含有CFC(CFC MDI)或HFA(HFA MDI)的MDI单次吸入1000微克FP后的药代动力学数据与单次静脉注射250微克FP后的药代动力学数据。
通过两种类型的MDI吸入后,血浆中FP的最大浓度几乎相同(CFC MDI和HFA MDI分别为0.56和0.54微克/升);两种MDI吸入的FP的生物利用度值也相似(几何平均值:通过CFC MDI为26.4%,通过HFA MDI为28.6%)。在给药后12小时和24小时内,通过两种MDI制剂吸入FP均使尿皮质醇排泄量产生相似程度的降低。
通过CFC MDI和HFA MDI吸入后FP的生物利用度值相似。两种制剂递送的FP量相当,并且通过尿皮质醇排泄量测量,两种装置使机体对FP的全身暴露无显著差异。