Steinijans V W, Trautmann H, Johnson E, Beier W
Byk Gulden Lung Research Center, Konstanz, F.R.G.
Chronobiol Int. 1987;4(3):331-47. doi: 10.3109/07420528709083523.
With the introduction of sustained-release theophylline formulations for once-daily dosing or for unequally divided twice-daily dosing, comparison with conventional equally divided twice-daily dosing has been focused on nocturnal serum theophylline concentrations (STCs), plateau properties and peak-trough fluctuation. The merits of various steady-state characteristics such as nocturnal excess, plateau time, residual concentration, peak-trough fluctuation, swing and AUC fluctuation are illustrated by 15 data sets from 7 multiple-dose studies, each including either 10-12 healthy volunteers or 12-20 COPD-patients. In all of the studies, STCs were determined at least every 2 hr over a 24-hr period in steady-state. Included in the studies were 7 sustained-release theophylline formulations which were administered either once daily (in the morning or in the evening), or twice daily (either equally divided, or unequally divided with one-third of the dose being given in the morning and two-thirds in the evening.
随着用于每日一次给药或不平均两次给药的缓释茶碱制剂的引入，与传统的平均两次给药的比较主要集中在夜间血清茶碱浓度（STC）、平台期特性以及峰谷波动上。通过来自7项多剂量研究的15组数据说明了各种稳态特征的优点，如夜间过量、平台期时间、残留浓度、峰谷波动、摆动和AUC波动，每项研究包括10至12名健康志愿者或12至20名慢性阻塞性肺疾病（COPD）患者。在所有研究中，在稳态的24小时期间至少每2小时测定一次STC。这些研究中包括7种缓释茶碱制剂，它们要么每日一次给药（早晨或晚上），要么每日两次给药（要么平均分配，要么不平均分配，三分之一剂量在早晨给药，三分之二在晚上给药）。
