Brannan M D, Herron J M, Reidenberg P, Affrime M B
Schering-Plough Research Institute, Kenilworth, New Jersey 07033, USA.
Ann Allergy Asthma Immunol. 1998 Jan;80(1):39-44. doi: 10.1016/S1081-1206(10)62937-7.
The efficacy and safety of regular-strength beclomethasone dipropionate MDI prescribed within its recommended dosing range of 2 to 5 puffs three to four times daily has been well established in more than 25 years of worldwide use. A more concentrated formulation delivering 84 microg per puff was developed to provide for a more convenient twice-daily dosing regimen.
This randomized, single-blinded, positive and placebo-controlled, parallel-group, multiple-dose bioactivity study was conducted to assess the potential of a new beclomethasone dipropionate 84 microg double-strength metered-dose inhaler (Vanceril 84 microg Double Strength Inhalation Aerosol/Key) to cause hypothalamic-pituitary-adrenocortical axis suppression.
Beclomethasone dipropionate double-strength 84 microg was compared with beclomethasone dipropionate regular-strength 42 microg, orally administered prednisone, and placebo inhaler after 36 consecutive days of administration in adults with moderate asthma. Beclomethasone dipropionate double-strength was administered as 5 puffs BID and beclomethasone dipropionate regular-strength was administered as 10 puffs BID for the same total daily dose of 840 microg of beclomethasone dipropionate. Oral prednisone was administered by mouth at 10 mg once a day. The potential for hypothalamic-pituitary-adrenocortical axis suppression was evaluated by an adrenocorticotropic hormone (ACTH) stimulation test using cosyntropin 250 microg in 500 mL normal saline infused over six hours on the 36th day of treatment. Sixty-four patients completed this study.
No clinically significant post-study findings were observed from physical examination, electrocardiogram, or clinical laboratory evaluation for any treatment group. No serious or unexpected adverse events were reported. On the 36th day of treatment, there was a significant (P < .01) difference in the plasma cortisol concentration response to cosyntropin stimulation between the prednisone and placebo treatment groups at the sixth hour of infusion. There was no significant difference in the plasma cortisol concentration response to cosyntropin stimulation between the beclomethasone dipropionate double-strength and beclomethasone dipropionate regular-strength treatment groups and the placebo group. In addition, comparison of the response between the beclomethasone dipropionate double-strength and beclomethasone dipropionate regular-strength groups showed no significant difference.
Beclomethasone dipropionate, administered either via a double-strength (84 microg/puff) or regular-strength (42 microg/puff) inhaler dosed at 840 microg/day showed no evidence of hypothalamic-pituitary-adrenocortical axis suppression in adults with moderate asthma.
在全球超过25年的使用中，已充分证实了丙酸倍氯米松定量气雾剂常规剂量在每日2至5喷、每日三至四次的推荐剂量范围内的有效性和安全性。已研发出一种每喷含84微克的更浓缩制剂，以便提供更方便的每日两次给药方案。
进行这项随机、单盲、阳性和安慰剂对照、平行组、多剂量生物活性研究，以评估新型每喷含84微克丙酸倍氯米松双剂量定量吸入器（万托林84微克双剂量吸入气雾剂/凯）导致下丘脑-垂体-肾上腺皮质轴抑制的可能性。
在中度哮喘成年患者连续给药36天后，将每喷含84微克的丙酸倍氯米松双剂量制剂与每喷含42微克的丙酸倍氯米松常规剂量制剂、口服泼尼松及安慰剂吸入器进行比较。丙酸倍氯米松双剂量制剂每日两次、每次5喷给药，丙酸倍氯米松常规剂量制剂每日两次、每次10喷给药，两种制剂的丙酸倍氯米松每日总剂量均为840微克。口服泼尼松每日10毫克。在治疗第36天，通过促肾上腺皮质激素（ACTH）刺激试验评估下丘脑-垂体-肾上腺皮质轴抑制的可能性。该试验使用250微克合成促肾上腺皮质激素，加入500毫升生理盐水中，在6小时内输注。64名患者完成了本研究。
任何治疗组在体格检查、心电图或临床实验室评估中均未观察到具有临床意义的研究后结果。未报告严重或意外不良事件。在治疗第36天，输注6小时时，泼尼松治疗组与安慰剂治疗组在合成促肾上腺皮质激素刺激后的血浆皮质醇浓度反应存在显著差异（P < 0.01）。丙酸倍氯米松双剂量制剂治疗组和丙酸倍氯米松常规剂量制剂治疗组与安慰剂组在合成促肾上腺皮质激素刺激后的血浆皮质醇浓度反应无显著差异。此外，丙酸倍氯米松双剂量制剂组与丙酸倍氯米松常规剂量制剂组之间的反应比较也无显著差异。
对于中度哮喘成年患者，每日剂量为840微克的丙酸倍氯米松，无论是通过双剂量（每喷84微克）还是常规剂量（每喷42微克）吸入器给药，均未显示下丘脑-垂体-肾上腺皮质轴抑制的证据。
