Thompson P J, Davies R J, Young W F, Grossman A B, Donnell D
Department of Medicine, University of Western Australia.
Respir Med. 1998 Jun;92 Suppl A:33-9. doi: 10.1016/s0954-6111(98)90215-3.
Herein we assess the safety of an inhaled formulation of beclomethasone dipropionate (BDP) which uses the propellant hydrofluoroalkane-134a (HFA) for the treatment of asthma. Acute local tolerability (as assessed by the incidence of cough and mean forced expiratory volume after 1 s inhalation) was similar for both BDP and placebo formulated in either chlorofluorocarbon (CFC) or HFA propellants. A total of 43 patients were treated with HFA-BDP (0, 200, 400 or 800 micrograms day-1) or CFC-BDP (800 micrograms day-1) for 14 days and their 24 h urinary free cortisol (UFC) excretion and response to cosyntropin stimulation were measured. There was no difference in UFC between any of the doses of HFA-BDP and CFC-BDP. Adrenal responsiveness to cosyntropin stimulation was normal in all but one patient. Two large 12 week phase III trials compared HFA-placebo, HFA-BDP 400 micrograms day-1 and CFC-BDP 800 micrograms day-1 (n = 347), and HFA-BDP 800 micrograms day-1 and CFC-BDP 1500 micrograms day-1 (n = 233). For HFA-BDP at either dose, CFC-BDP 800 micrograms day-1 and HFA-placebo, the number of patients with morning plasma cortisol concentrations below normal was less than 4.4% but was 14.6% for CFC-BDP 1500 micrograms day-1. The incidence of adverse events was lower in the HFA-BDP groups than in the CFC-BDP groups (P = 0.012). The data indicate that, at doses of up to 800 micrograms day-1, HFA-BDP is at least as well tolerated as CFC-BDP. Other studies have found that equivalent efficacy is reached at lower doses of HFA-BDP than CFC-BDP. Equivalent efficacy at a lower dose and equivalent safety at the same dose imply that HFA-BDP may have a more favourable risk: benefit ratio than CFC-BDP when used at the recommended lower doses.
在此，我们评估了一种使用氢氟烷烃-134a（HFA）作为推进剂的丙酸倍氯米松（BDP）吸入制剂治疗哮喘的安全性。对于用氯氟烃（CFC）或HFA推进剂配制的BDP和安慰剂，急性局部耐受性（通过咳嗽发生率和吸入1秒后的平均用力呼气量评估）相似。共有43例患者接受HFA-BDP（0、200、400或800微克/天）或CFC-BDP（800微克/天）治疗14天，并测量其24小时尿游离皮质醇（UFC）排泄量和对促肾上腺皮质激素刺激的反应。任何剂量的HFA-BDP与CFC-BDP之间的UFC均无差异。除一名患者外，所有患者对促肾上腺皮质激素刺激的肾上腺反应均正常。两项为期12周的大型III期试验比较了HFA-安慰剂、400微克/天的HFA-BDP和800微克/天的CFC-BDP（n = 347），以及800微克/天的HFA-BDP和1500微克/天的CFC-BDP（n = 233）。对于任一剂量的HFA-BDP、800微克/天的CFC-BDP和HFA-安慰剂，早晨血浆皮质醇浓度低于正常的患者人数少于4.4%，但对于1500微克/天的CFC-BDP，这一比例为14.6%。HFA-BDP组的不良事件发生率低于CFC-BDP组（P = 0.012）。数据表明，在高达800微克/天的剂量下，HFA-BDP的耐受性至少与CFC-BDP相当。其他研究发现，与CFC-BDP相比，较低剂量的HFA-BDP即可达到同等疗效。较低剂量时同等疗效且相同剂量时同等安全性意味着，在推荐的较低剂量使用时，HFA-BDP可能比CFC-BDP具有更有利的风险效益比。
