Reed R C, Schwartz H J
Ther Drug Monit. 1986;8(2):155-60. doi: 10.1097/00007691-198606000-00005.
The temporal variation in trough (i.e., predose) theophylline concentrations at steady state was examined. In general, adult subjects dosed with solid theophylline formulations have morning trough theophylline concentrations 10-16% greater than corresponding evening troughs; this morning-to-evening drop is statistically significant. Large-percentage diurnal changes (greater than +/- 20% and even greater than or equal to +/- 40%) in trough-to-trough serum theophylline concentrations are not uncommon in adults. However, the change in absolute trough theophylline concentrations is pronounced in only some individuals. Repetitive studies in four of five individuals tested generally demonstrated within-individual reproducibility in the direction (but not magnitude) of the temporal variation in trough theophylline concentration. This finding further substantiates the morning-to-evening change in trough theophylline concentration as a real phenomenon and not merely the result of random variability. It is believed that the temporal variability in trough concentration observed after peroral theophylline administration requires monitoring theophylline dosage needs by obtaining blood samples at the same time each day.
对稳态时茶碱谷浓度（即给药前浓度）的时间变化进行了研究。一般来说，服用固体茶碱制剂的成年受试者早晨的茶碱谷浓度比相应的晚上谷浓度高10 - 16%；这种从早晨到晚上的下降具有统计学意义。成人血清茶碱谷浓度在谷值到谷值之间出现较大百分比的日间变化（大于+/- 20%，甚至大于或等于+/- 40%）并不罕见。然而，绝对茶碱谷浓度的变化仅在部分个体中较为明显。对五名受试者中的四名进行的重复研究通常表明，茶碱谷浓度时间变化的方向（而非幅度）在个体内部具有可重复性。这一发现进一步证实了茶碱谷浓度从早晨到晚上的变化是一种真实现象，而不仅仅是随机变异的结果。据信，口服茶碱后观察到的谷浓度时间变异性需要通过每天在同一时间采集血样来监测茶碱的剂量需求。
