Wilson A M, Brewster H J, Lipworth B J
Department of Clinical Pharmacology and Therapeutics, Ninewells Hospital & Medical School, University of Dundee, Dundee, Scotland, UK.
J Allergy Clin Immunol. 1998 Nov;102(5):751-6. doi: 10.1016/s0091-6749(98)70014-4.
Budesonide (BUD) has recently been licensed for treatment of asthma in the United States, whereas triamcinolone acetonide (TAA) has been used for many years.
We sought to evaluate the dose-response effect of inhaled BUD and TAA in terms of adrenal, bone, and blood markers.
Twelve asthmatic subjects (mean age, 32 years; mean FEV1, 91% of predicted value) were studied in a randomized design comparing 3 days of treatment with placebo and low (200 micrograms twice daily), medium (400 micrograms twice daily), and high (800 micrograms twice daily) doses of BUD (Pulmicort Turbuhaler, 100 micrograms) and TAA (Azmacort integrated actuator/spacer, 100 micrograms) with a 7-day period at crossover, when patients received their usual inhaled corticosteroid therapy. Measurements were made at 8 am for serum cortisol, osteocalcin, and blood eosinophils. Measurements were also made for overnight urinary cortisol/creatinine excretion.
For all measurements there were no significant differences between the 2 treatments at any dose level. Ratios between BUD and TAA (95% CI) at the highest dose levels were as follows: 8 am serum cortisol, 1.08-fold (0.63 to 1. 85); urinary cortisol, 1.09-fold (0.63 to 1.86); eosinophils, 0. 98-fold (0.69 to 1.38); and osteocalcin 1.05-fold (0.78 to 1.41). There was no evidence of a significant overall dose-response effect for any parameter of hypothalamo-pituitary-adrenocortical axis activity, with neither drug being significantly different from placebo at any dose. For the 3 dose levels of both drugs, total abnormal low values for 8 am serum cortisol (ie, <5.4 micrograms/dL [<150 nmol/L]) showed 2 of 36 for BUD and 2 of 36 for TAA. There was also no significant overall dose-response effect for eosinophils or osteocalcin, although both drugs were significantly (P <.05) different from placebo at the highest dose: eosinophils (x10(9)/L), placebo: 0.36, TAA: 0.24, and BUD: 0.23; and osteocalcin (nmol/L), placebo: 1.04, TAA: 0.73, and BUD: 0.77.
There were no significant differences in the systemic bioactivity profiles, in terms of adrenal, blood, and bone markers, between BUD administered by means of Turbuhaler and TAA administered by means of an integrated actuator/spacer in a dose range of 400 micrograms to 1600 micrograms/day. Both drugs exhibited a significant degree of detectable systemic bioactivity but only at the highest dose of 1600 micrograms/day for effects on eosinophil count and osteocalcin.
布地奈德（BUD）最近在美国被批准用于治疗哮喘，而曲安奈德（TAA）已使用多年。
我们试图从肾上腺、骨骼和血液标志物方面评估吸入性布地奈德和曲安奈德的剂量反应效应。
12名哮喘患者（平均年龄32岁；平均第一秒用力呼气容积[FEV1]为预测值的91%）参与了一项随机设计研究，比较了3天的安慰剂治疗以及低剂量（每日两次，每次200微克）、中剂量（每日两次，每次400微克）和高剂量（每日两次，每次800微克）的布地奈德（普米克都保，每吸100微克）和曲安奈德（必可酮吸入气雾剂/储物罐，每吸100微克）治疗，治疗周期为7天，期间患者接受其常规吸入性糖皮质激素治疗。上午8点测量血清皮质醇、骨钙素和血液嗜酸性粒细胞。还测量了过夜尿皮质醇/肌酐排泄量。
对于所有测量指标，两种治疗在任何剂量水平下均无显著差异。最高剂量水平下布地奈德与曲安奈德的比值（95%置信区间）如下：上午8点血清皮质醇，1.08倍（0.63至1.85）；尿皮质醇，1.09倍（0.63至1.86）；嗜酸性粒细胞，0.98倍（0.69至1.38）；骨钙素，1.05倍（0.78至1.41）。下丘脑 - 垂体 - 肾上腺皮质轴活动的任何参数均无明显的总体剂量反应效应证据，两种药物在任何剂量下与安慰剂均无显著差异。对于两种药物的3个剂量水平，上午8点血清皮质醇的总异常低值（即，<5.4微克/分升[<150纳摩尔/升]）在布地奈德的36次测量中有2次，曲安奈德的36次测量中有2次。嗜酸性粒细胞或骨钙素也无明显的总体剂量反应效应，尽管两种药物在最高剂量时与安慰剂有显著差异（P<.05）：嗜酸性粒细胞（×10⁹/升），安慰剂：0.36，曲安奈德：0.24，布地奈德：0.23；骨钙素（纳摩尔/升），安慰剂：1.04，曲安奈德：0.73，布地奈德：0.77。
在通过都保装置给药的布地奈德和通过吸入气雾剂/储物罐给药的曲安奈德之间，就肾上腺、血液和骨骼标志物而言，在400微克至1600微克/天的剂量范围内，全身生物活性特征无显著差异。两种药物均表现出显著程度的可检测到的全身生物活性，但仅在最高剂量1600微克/天时对嗜酸性粒细胞计数和骨钙素有影响。
