Reinberg A, Gervais P, Chaussade M, Fraboulet G, Duburque B
J Allergy Clin Immunol. 1983 Apr;71(4):425-33. doi: 10.1016/0091-6749(83)90073-8.
A double-blind, crossover, randomized, placebo-controlled chronotherapeutic study was designed in which eight patients (two men, 20 and 48 yr old, and six women, 22 to 58 yr old) suffering from corticosteroid-dependent allergic asthma were socially synchronized, with a diurnal activity from about 7:30 A.M. to about 11 P.M. and a nocturnal rest. During an 8 day span they were treated on a Dutimelan 8-15 regimen, labeled DTM 8-15: at 8 A.M. a pill containing 7 mg of prednisolone acetate and 4 mg of prednisolone alcohol, at 3 P.M. a pill with 15 mg of cortisone acetate and 3 mg of prednisolone alcohol, and a placebo at 8 P.M. During another 8 day span they were given a placebo at 8 A.M. and at 3 P.M. a pill with 15 mg of cortisone acetate and 3 mg of prednisolone alcohol and at 8 P.M. another pill with 7 mg of prednisolone acetate and 4 mg of prednisolone alcohol, a regimen labeled Rx 15-20. During wakefulness (between 7 A.M. and 11 P.M.), every 2 hr at eight fixed clock hours, peak expiratory flow (PEF), grip strength, and oral temperature were self-measured and dyspnea, cough, and fatigue were self-rated. The PEF 24 hr mean as well as the nocturnal dip were lower (p less than 0.05 to p less than 0.0005) with Rx 15-20 than with DTM 8-15, while the nocturnal increase of dyspnea was greater with Rx 15-20 than with DTM 8-15. Long-term administration of corticosteroids at 8 A.M. and 3 P.M. was more effective to control asthma and enhance PEF values than the same agents and dose given at 3 and 8 P.M.
设计了一项双盲、交叉、随机、安慰剂对照的时间治疗研究，纳入8例依赖皮质类固醇的过敏性哮喘患者（2例男性，年龄分别为20岁和48岁；6例女性，年龄在22至58岁之间），使其社会活动时间同步，日间活动时间约为上午7:30至晚上11点，夜间休息。在8天的时间里，他们接受Dutimelan 8 - 15方案治疗，标记为DTM 8 - 15：上午8点服用一片含7毫克醋酸泼尼松龙和4毫克泼尼松龙醇的药丸，下午3点服用一片含15毫克醋酸可的松和3毫克泼尼松龙醇的药丸，晚上8点服用安慰剂。在另外8天的时间里，他们上午8点和下午3点服用安慰剂，晚上8点服用一片含7毫克醋酸泼尼松龙和4毫克泼尼松龙醇的药丸，该方案标记为Rx 15 - 20。在清醒期间（上午7点至晚上11点），每隔2小时在八个固定的时钟时间点，患者自行测量呼气峰值流速（PEF）、握力和口腔温度，并自行评估呼吸困难、咳嗽和疲劳程度。与DTM 8 - 15相比，Rx 15 - 20方案的24小时平均PEF以及夜间下降幅度更低（p小于0.05至p小于0.0005），而Rx 15 - 20方案的夜间呼吸困难增加幅度大于DTM 8 - 15。上午8点和下午3点长期服用皮质类固醇比下午3点和晚上8点服用相同药物和剂量更有效地控制哮喘并提高PEF值。
