Tse F L, Valia K H, Szeto D W, Raimondo T J, Koplowitz B
J Pharm Sci. 1981 Apr;70(4):395-9. doi: 10.1002/jps.2600700414.
The pharmacokinetic interactions of caffeine with theophylline were examined in two beagle dogs by administering 100 mg of aminophylline intravenously, 3 weeks before and immediately after repeated oral doses of caffeine. Serial plasma samples were analyzed for caffeine and theophylline simultaneously by high-performance liquid chromatography. Upon multiple oral dosing, 100 mg every 12 hr for 7 days, the caffeine half-life increased slightly in one dog but decreased in the other. As predicted from single-dose data, caffeine accumulation in plasma after repeated doses was slight, while plasma levels of the N-demethylated metabolite, theophylline, rose to about three times the initial values. After rapid intravenous doses of aminophylline, the theophylline half-life was 5-7 hr, which decreased slightly when the drug was administered concomitantly with caffeine during steady state of caffeine. The theophylline volume of distribution (0.75 liter/kg) was unaffected by caffeine. On the other hand, an acute aminophylline injection prolonged the elimination half-life and increased the apparent volume of distribution of caffeine, causing little overall change in its plasma clearance. The results suggested that interactions between theophylline and caffeine may be attributed to changes in drug distribution and drug elimination characteristics.
通过在两只比格犬中静脉注射100毫克氨茶碱，并在重复口服咖啡因剂量前3周和之后立即进行，研究了咖啡因与茶碱的药代动力学相互作用。通过高效液相色谱法同时分析连续血浆样本中的咖啡因和茶碱。多次口服给药时，每12小时100毫克，共7天，一只狗的咖啡因半衰期略有增加，而另一只狗的则下降。正如单剂量数据所预测的，重复给药后血浆中的咖啡因积累轻微，而N-去甲基代谢物茶碱的血浆水平上升至初始值的约三倍。快速静脉注射氨茶碱后，茶碱的半衰期为5 - 7小时，在咖啡因稳态期间与咖啡因同时给药时略有下降。茶碱的分布容积（0.75升/千克）不受咖啡因影响。另一方面，急性氨茶碱注射延长了咖啡因的消除半衰期并增加了其表观分布容积，但其血浆清除率总体变化不大。结果表明，茶碱与咖啡因之间的相互作用可能归因于药物分布和药物消除特性的变化。
