Goldenheim P D, Conrad E A, Schein L K
Medical Department, Purdue Frederick Company, Norwalk, CT 06856.
Chronobiol Int. 1987;4(3):397-408. doi: 10.3109/07420528709083529.
As many as 80 percent of asthmatics experience nighttime or early-morning episodes, which are difficult to treat and potentially fatal. The greater-than-normal amplitude of circadian airflow variation in many asthmatics contributes heavily to the genesis of the early 'morning dip'. Beta-agonists and corticosteroids are of limited usefulness in nocturnal asthma, and slow-release theophylline drugs, while potentially effective, vary in 24-hr blood profile and hence their influence on nocturnal episodes. Traditional 12-hr 'symmetric' theophylline regimens, instead of meeting increased nocturnal demands, may actually produce lower night- than daytime blood levels. On the other hand, appropriately timed administration of a once-daily theophylline drug might provide maximum blood levels when needed and help stabilize 24-hr airflow. Accumulated data, summarized in this review, demonstrate the chronotherapeutic potential of single-daily evening doses of a controlled-release theophylline preparation (Uniphyl 400-mg tablets) in nocturnal and early morning asthma. Nighttime blood concentrations with this regimen were higher than were those with Theo-Dur tablets, B.I.D., in the same total daily doses, or with once-daily morning Uniphyl administration. In fed and fasted subjects, evening administration of Uniphyl 400-mg tablets was well tolerated and did not lead to 'dose dumping.' Clinically, this treatment demonstrated advantages over B.I.D. theophylline, over single-daily morning regimens, and over prior theophylline therapy. Advantages of the evening regimen included better early-morning airflow (without significant decline later in the day), more effective symptom control, better patient acceptance, fewer night awakenings, and the obvious convenience of once-daily dosing. In addition, lung function showed greater stability, throughout the day, with once-daily evening therapy than with traditional 12 hr dosing. Uniphyl 400-mg tablets may be administered once daily to provide maximum blood levels at the time of peak bronchoconstriction, whether at night or during the day.
多达80%的哮喘患者会经历夜间或清晨发作，这些发作难以治疗且可能致命。许多哮喘患者昼夜气流变化幅度大于正常水平，这在很大程度上导致了清晨低谷的出现。β受体激动剂和皮质类固醇在夜间哮喘中的作用有限，缓释茶碱药物虽然可能有效，但24小时血药浓度有所不同，因此它们对夜间发作的影响也不同。传统的12小时“对称”茶碱给药方案，非但不能满足夜间增加的需求，实际上可能导致夜间血药浓度低于白天。另一方面，每天一次的茶碱药物在适当时间给药，可能在需要时提供最高血药浓度，并有助于稳定24小时气流。本综述总结的累积数据表明，每日单次晚间服用控释茶碱制剂（优喘平400毫克片剂）对夜间和清晨哮喘具有时辰治疗潜力。采用该方案时，夜间血药浓度高于相同每日总剂量的舒弗美片剂每日两次给药，或优喘平每日一次清晨给药。在进食和空腹的受试者中进行的研究表明，晚间服用优喘平400毫克片剂耐受性良好，不会导致“剂量倾泻”。临床上，这种治疗方法相对于每日两次的茶碱治疗、每日一次的清晨给药方案以及先前的茶碱治疗均显示出优势。晚间给药方案的优势包括更好的清晨气流（白天晚些时候无明显下降）、更有效的症状控制、患者接受度更高、夜间觉醒次数更少以及每日一次给药明显的便利性。此外，与传统的12小时给药相比，每日一次晚间治疗使肺功能在一整天中表现出更大的稳定性。优喘平400毫克片剂可每日给药一次，无论在夜间还是白天，均可在支气管收缩高峰期提供最高血药浓度。
