Sorkness C A, LaForce C, Storms W, Lincourt W R, Edwards L, Rogenes P R
University of Wisconsin Hospital and Clinics, Madison 53792, USA.
Clin Ther. 1999 Feb;21(2):353-67. doi: 10.1016/S0149-2918(00)88292-2.
Two multicenter, randomized, double-masked, placebo-controlled, parallel-group studies were conducted in adult patients with mild-to-moderate persistent asthma to assess the effects of 4 weeks of treatment with inhaled corticosteroids on hypothalamic-pituitary-adrenal (HPA) axis function. The first study compared fluticasone propionate 100 and 500 microg twice daily, triamcinolone acetonide 300 and 500 microg twice daily, oral prednisone 10 mg every morning, and placebo. The second study compared fluticasone propionate 100 and 250 microg twice daily, flunisolide 500 microg twice daily, and placebo. Therapeutic doses of fluticasone propionate, triamcinolone acetonide, and flunisolide were found to be comparable to each other and to placebo in their lack of adrenal suppressive effects, based on mean plasma cortisol responses to 6-hour cosyntropin infusion. Prednisone produced significantly greater suppression of HPA-axis function than did any of the inhaled corticosteroids or placebo (P<0.001). Mean reductions from baseline in 8-hour area under the plasma concentration-time curve (AUC) and 8-hour peak plasma cortisol concentrations and the mean percentage of change from baseline in 8-hour AUC were significantly greater after treatment with triamcinolone acetonide 500 microg twice daily compared with placebo (P< or =0.042). These findings indicate that fluticasone propionate has no greater systemic effect than either triamcinolone acetonide or flunisolide at doses appropriate for patients with mild-to-moderate persistent asthma.
开展了两项多中心、随机、双盲、安慰剂对照、平行组研究,以评估吸入性糖皮质激素治疗4周对轻至中度持续性哮喘成年患者下丘脑-垂体-肾上腺(HPA)轴功能的影响。第一项研究比较了每日两次吸入丙酸氟替卡松100和500微克、每日两次吸入曲安奈德300和500微克、每日早晨口服泼尼松10毫克以及安慰剂的效果。第二项研究比较了每日两次吸入丙酸氟替卡松100和250微克、每日两次吸入氟尼缩松500微克以及安慰剂的效果。基于对6小时促肾上腺皮质激素输注的平均血浆皮质醇反应,发现丙酸氟替卡松、曲安奈德和氟尼缩松的治疗剂量在缺乏肾上腺抑制作用方面彼此相当且与安慰剂相当。泼尼松对HPA轴功能的抑制作用明显大于任何一种吸入性糖皮质激素或安慰剂(P<0.001)。与安慰剂相比,每日两次吸入500微克曲安奈德治疗后,血浆浓度-时间曲线下8小时面积(AUC)、8小时血浆皮质醇峰值浓度较基线的平均降低幅度以及8小时AUC较基线变化的平均百分比均显著更大(P≤0.042)。这些发现表明,对于轻至中度持续性哮喘患者,在适当剂量下,丙酸氟替卡松的全身作用并不比曲安奈德或氟尼缩松更大。