Martin Richard J, Szefler Stanley J, Chinchilli Vernon M, Kraft Monica, Dolovich Myrna, Boushey Homer A, Cherniack Reuben M, Craig Timothy J, Drazen Jeffrey M, Fagan Joanne K, Fahy John V, Fish James E, Ford Jean G, Israel Elliott, Kunselman Susan J, Lazarus Stephen C, Lemanske Robert F, Peters Stephen P, Sorkness Christine A
National Jewish Medical and Research Center, Denver, Colorado 80206, USA.
Am J Respir Crit Care Med. 2002 May 15;165(10):1377-83. doi: 10.1164/rccm.2105013.
The goal of this study was to establish a reliable method to evaluate systemic bioavailability and to determine equisystemic effects (microgram dose producing equal systemic cortisol suppression) of inhaled corticosteroids (ICS). Steroid naive asthma subjects (n = 156) were enrolled at six centers. A 1-week doubling dose design was used for each of six ICS and matched placebos for a total of four doses. Systemic effect was evaluated by hourly plasma cortisol concentrations (8 P.M. to 8 A.M.), 12- and 24-hour urine cortisol concentrations, and a morning blood osteocalcin. The area under the concentration-time curve for hourly cortisol concentrations was the best outcome variable to assess systemic effect. For the six ICS and matching placebos (beclomethasone-chlorofluorocarbon [CFC], budesonide dry powder inhaler [DPI], fluticasone DPI, fluticasone-CFC metered dose inhaler [MDI], flunisolide-CFC, and triamcinolone-CFC), only the placebo group and fluticasone DPI did not demonstrate a significant dose-response effect. Thus microgram comparison of all ICS could only be performed at a 10% cortisol suppression: flunisolide-CFC - 936; triamcinolone-CFC - 787; beclomethasone-CFC - 548; fluticasone DPI - 445; budesonide DPI - 268; fluticasone-CFC MDI - 111. This study represents the first step in evaluation of ICS efficacy based on equisystemic (cortisol suppression) effects of a given ICS, rather than doses judged arbitrarily to be comparable on a microgram basis.
本研究的目的是建立一种可靠的方法来评估全身生物利用度，并确定吸入性糖皮质激素（ICS）的等效全身效应（产生同等全身皮质醇抑制作用的微克剂量）。在六个中心招募了未使用过类固醇的哮喘受试者（n = 156）。对六种ICS及相应的安慰剂采用1周剂量加倍设计，共四个剂量。通过每小时血浆皮质醇浓度（晚上8点至上午8点）、12小时和24小时尿皮质醇浓度以及早晨血液骨钙素评估全身效应。每小时皮质醇浓度的浓度-时间曲线下面积是评估全身效应的最佳结果变量。对于六种ICS及其相应的安慰剂（倍氯米松-氯氟烃[CFC]、布地奈德干粉吸入器[DPI]、氟替卡松DPI、氟替卡松-CFC定量吸入器[MDI]、氟尼缩松-CFC和曲安西龙-CFC），只有安慰剂组和氟替卡松DPI未显示出显著的剂量反应效应。因此，所有ICS的微克比较只能在皮质醇抑制10%时进行：氟尼缩松-CFC - 936；曲安西龙-CFC - 787；倍氯米松-CFC - 548；氟替卡松DPI - 445；布地奈德DPI - 268；氟替卡松-CFC MDI - 111。本研究代表了基于给定ICS的等效全身（皮质醇抑制）效应而非任意判断为微克基础上可比的剂量来评估ICS疗效的第一步。
