Jackson S H, Wiffen J K, Smythe M M, Johnston A
Br J Clin Pharmacol. 1984 Jun;17(6):777-9. doi: 10.1111/j.1365-2125.1984.tb02419.x.
Ten healthy volunteers were each given two separate courses of eight doses of theophylline 200 mg as a slow release preparation at 12 hourly intervals. In the first course (regimen 1) the dose was given at 11.00 h and 23.00 h and in the second (regimen 2) at 05.00 h and 17.00 h. Sixty hours after the start of each course, four consecutive trough serum theophylline concentrations were measured. On regimen 1 the trough concentration of theophylline was 6.2 +/- 2.2 mg/l (mean +/- s.d.) at 11.00 h compared with 5.4 +/- 1.9 mg/l at 23.00 h (P less than 0.01). This circadian variation was abolished during regimen 2 when the mean theophylline concentrations were identical at 5.2 mg/l. The higher trough concentrations after the evening dose on regimen 1 and the loss of circadian variation on regimen 2 may be due to the change in sleep period in relation to the time of dosing.
十名健康志愿者每人接受两个疗程的治疗，每个疗程为八剂200毫克的缓释型茶碱，给药间隔为12小时。在第一个疗程（方案1）中，给药时间为上午11点和晚上11点；在第二个疗程（方案2）中，给药时间为凌晨5点和下午5点。每个疗程开始60小时后，连续测量四次茶碱血药谷浓度。在方案1中，上午11点时茶碱的谷浓度为6.2±2.2毫克/升（平均值±标准差），而晚上11点时为5.4±1.9毫克/升（P<0.01）。在方案2中，这种昼夜变化消失了，此时茶碱的平均浓度为5.2毫克/升且保持一致。方案1中晚上给药后较高的谷浓度以及方案2中昼夜变化的消失，可能是由于睡眠时间与给药时间的关系发生了变化。
