Sato J, Nakata H, Owada E, Kikuta T, Umetsu M, Ito K
Hokkaido Institute of Pharmaceutical Sciences, Japan.
Eur J Clin Pharmacol. 1993;44(3):295-8. doi: 10.1007/BF00271376.
The influence of usual multiple ingestions of dietary caffeine on oral single-dose pharmacokinetics of theophylline has been investigated in 6 healthy male subjects. The subjects consumed 2 to 7 cups of regular instant coffee during the 24 h study period. Their mean serum concentrations of caffeine varied from 1.2 to 3.1 mg/l. After their usual intake of dietary caffeine, the serum concentrations of theophylline from 3 to 24 h after administration were significantly higher than after deprivation of dietary caffeine. The apparent elimination of theophylline half-life was prolonged from 6.3 (0.61) h (mean with (SEM)) to 8.3 (0.47) h (32% increase, P < 0.01) and the total body clearance was reduced from 55.0 (1.31) ml.h-1.kg-1 to 42.5 (2.63) ml.h-1.kg-1 (23% decrease, P < 0.001). Saturation of theophylline metabolism and/or competition between theophylline and caffeine metabolism in addition to theophylline derived from caffeine may be the cause of the delayed elimination of theophylline. The present study has indicated that a significant reduction in theophylline metabolism may be caused by a conventional intake of dietary caffeine. In bronchodilator therapy with theophylline, therefore, the daily consumption of caffeine should be taken into consideration.
在6名健康男性受试者中研究了日常多次摄入膳食咖啡因对口服单剂量茶碱药代动力学的影响。在24小时的研究期间，受试者饮用了2至7杯普通速溶咖啡。他们的咖啡因平均血清浓度在1.2至3.1毫克/升之间。在他们日常摄入膳食咖啡因后，给药后3至24小时的茶碱血清浓度显著高于剥夺膳食咖啡因后。茶碱的表观消除半衰期从6.3（0.61）小时（平均值及标准误）延长至8.3（0.47）小时（增加32%，P<0.01），全身清除率从55.0（1.31）毫升·小时-1·千克-1降至42.5（2.63）毫升·小时-1·千克-1（降低23%，P<0.001）。除了来自咖啡因的茶碱外，茶碱代谢的饱和和/或茶碱与咖啡因代谢之间的竞争可能是茶碱消除延迟的原因。本研究表明，常规摄入膳食咖啡因可能导致茶碱代谢显著降低。因此，在使用茶碱进行支气管扩张治疗时，应考虑每日咖啡因的摄入量。
