Systemic effect comparisons of six inhaled corticosteroid preparations
Systemic effect comparisons of six inhaled corticosteroid preparations
复制标题
DOI：
10.1164/rccm.2105013
复制
发表时间：
2002-05-15
影响因子：
24.7
通讯作者：
Sorkness, CA
中科院分区：
文献类型：
--
作者：
Martin, RJ;Szefler, SJ;Sorkness, CA
本研究的目的是建立一个可靠的方法来评估全身生物利用度和确定等系统效应（微克剂量产生相等的全身皮质醇抑制）吸入皮质类固醇（ICS）。在6个中心入组了未接受过类固醇治疗的哮喘受试者（n=156）。6种ICS和匹配安慰剂均采用1周加倍剂量设计，共4次给药。通过每小时血浆皮质醇浓度（晚上8点至早上8点）评价全身效应，12-24小时尿皮质醇浓度和晨血骨钙素。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局变量。对于6种ICS和匹配的安慰剂（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和曲安奈德-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10%皮质醇抑制下进行：氟尼缩松-CFC-936;曲安奈德-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的等系统（皮质醇抑制）效应评价ICS疗效的第一步，而不是在微克基础上任意判断为相当的剂量。
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.