Wilson A M, Clark D J, Devlin M M, McFarlane L C, Lipworth B J
Department of Clinical Pharmacology and Respiratory Medicine, Ninewells Hospital and Medical School, University of Dundee, Scotland, UK.
Eur J Clin Pharmacol. 1998 Jan;53(5):317-20. doi: 10.1007/s002280050385.
The aim of this study was to evaluate the steady-state effects of once-daily inhaled fluticasone propionate (FP) and budesonide (BUD) on adrenocortical activity in asthmatic patients.
Ten asthmatic patients with a mean age of 31.2 years, a mean forced expiratory volume in 1 s (FEV1) of 91% predicted and a forced mid-expiratory flow (FEF25-75) of 62.3% predicted were studied in a single-blind randomised crossover design comparing placebo (PL), FP (375 microg per day and 750 microg per day) and BUD (400 microg per day and 800 microg per day) all given once daily for 4 days at each dose via a pressurised metered dose inhaler (pMDI) at 0800 hours. After 4 days of treatment, plasma cortisol was measured at 0800 hours (24 h after the last dose) and a 10-h overnight urine collection was taken, 14 h after the last dose (2200-0800 hours) for analysis of cortisol and creatinine excretion.
Plasma cortisol levels (nmol.l(-1), as geometric mean) at 0800 hours demonstrated a significant difference between the highest doses of FP and BUD (424.1 vs 510.3 nmol.l(-1), respectively) but not between the low doses (506.8 vs 514.9 nmol.l(-1); PL 532.2 nmol.l(-1)). For the highest dose FP (750 microg) this equated to 20% suppression of 0800 hours plasma cortisol. Likewise, for overnight urinary cortisol output (nmol.10 h(-1) as geometric mean), there was a significant difference at the high doses of FP and BUD (25.5 vs 38.2 nmol.10 h(-1)), but not at the low doses 31.3 vs 34.8 nmol.10 h(-1); PL 32.0 nmol.10 h(-1). For the overnight urinary cortisol/creatinine ratio (nmol.mmol(-1), as geometric mean) there was a similar trend; 4.5 vs 6.1 nmol.mmol(-1) for high dose and 5.6 vs 6.3 nmol.mmol(-1) for low dose; PL 5.9 nmol.mmol(-1).
Repeated doses of FP 750 microg once daily caused greater adrenal suppression than BUD 800 microg once daily, when comparing effects on plasma cortisol levels at 0800 hours, 24 h after the last dose, as well as effects on overnight urinary cortisol output. Neither FP 375 microg once daily nor BUD 400 microg once daily produced detectable adrenal suppression.
本研究旨在评估每日一次吸入丙酸氟替卡松（FP）和布地奈德（BUD）对哮喘患者肾上腺皮质活性的稳态影响。
采用单盲随机交叉设计，对10名平均年龄31.2岁、一秒用力呼气容积（FEV1）平均为预测值的91%、用力呼气中期流速（FEF25 - 75）平均为预测值的62.3%的哮喘患者进行研究，比较安慰剂（PL）、FP（每日375微克和每日750微克）和BUD（每日400微克和每日800微克），所有药物均通过压力定量吸入器（pMDI）于08:00每日给药一次，每种剂量给药4天。治疗4天后，于08:00（最后一剂后24小时）测量血浆皮质醇，并在最后一剂后14小时（22:00 - 08:00）进行10小时夜间尿液收集，以分析皮质醇和肌酐排泄。
08:00时的血浆皮质醇水平（nmol·l⁻¹，几何均值）显示，FP和BUD的最高剂量之间存在显著差异（分别为每升424.1纳摩尔和510.3纳摩尔），但低剂量之间无显著差异（每升506.8纳摩尔和514.9纳摩尔；PL为每升532.2纳摩尔）。对于最高剂量的FP（750微克），这相当于抑制了08:00时血浆皮质醇的20%。同样，对于夜间尿皮质醇排出量（nmol·10小时⁻¹，几何均值），FP和BUD的高剂量之间存在显著差异（每10小时25.5纳摩尔和38.2纳摩尔），但低剂量之间无显著差异（每10小时31.3纳摩尔和34.8纳摩尔；PL为每10小时32.0纳摩尔）。对于夜间尿皮质醇/肌酐比值（nmol·mmol⁻¹，几何均值）也有类似趋势；高剂量为每毫摩尔4.5纳摩尔和6.1纳摩尔，低剂量为每毫摩尔5.6纳摩尔和6.3纳摩尔；PL为每毫摩尔5.9纳摩尔。
在比较最后一剂后24小时08:00时对血浆皮质醇水平的影响以及对夜间夜间夜间尿皮质醇排出量的影响时，每日一次重复给予FP 750微克比每日一次给予BUD 800微克引起的肾上腺抑制作用更强。每日一次给予FP 375微克或每日一次给予BUD 400微克均未产生可检测到的肾上腺抑制作用。
