EFFECTS OF CAFFEINE WITH REPEATED DOSING
EFFECTS OF CAFFEINE WITH REPEATED DOSING
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DOI：
10.1007/bf00315208
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发表时间：
1991-01-01
影响因子：
2.9
通讯作者：
BENOWITZ, NL
中科院分区：
文献类型：
--
作者：
DENARO, CP;BROWN, CR;BENOWITZ, NL
我们最近证明了在多次给药条件下咖啡因代谢的剂量依赖性。 在这种情况下，咖啡因是否具有持续的药效作用是本报告的重点。 9名健康受试者被随机分为5天、安慰剂、4.2（低）和12（高）mg·kg-1·d-1咖啡因6次给药，5天后，对咖啡因对血压、心率和血糖浓度的影响完全耐受。 血浆去甲肾上腺素的24小时曲线下面积（AUC）和游离脂肪酸（FFA）总和的AUC均显示出随着高剂量咖啡因治疗而增加的趋势。 当去甲肾上腺素的AUC分为12小时的时间段，安慰剂和高剂量治疗块之间的显着差异被seeed.We得出结论，经常消费的12毫克·千克-1的咖啡因每天（相当于约6至11杯咖啡每天）可能会产生药效学效应不完全补偿的耐受性的发展。 当咖啡因代谢达到饱和时，耐受机制可能会被体内咖啡因和其他甲基黄嘌呤的非线性积累所压倒。
We have recently demonstrated dose-dependency of caffeine metabolism under multiple dosing conditions. Whether there are persistent pharmacodynamic actions of caffeine under such circumstances is the focus of this report. Nine healthy subjects were given, in randomized 5 day blocks, placebo, 4.2 (low) and 12 (high) mg.kg-1.day-1 of caffeine in 6 divided doses.After 5 days, complete tolerance developed to the effects of caffeine on blood pressure, heart rate and plasma glucose concentrations. The 24-h area under the curve (AUC) for plasma norepinephrine and the AUC for the total sum of free fatty acids (FFA) both demonstrated a trend to increase with the high dose caffeine treatment. When the AUC for norepinephrine was split into 12 h time periods, a significant difference between the placebo and the high dose treatment block was seen.We conclude that regular consumption of 12 mg.kg-1 of caffeine per day (equivalent to approximately 6 to 11 cups of coffee per day) may produce pharmacodynamic effects not completely compensated for by the development of tolerance. Mechanisms of tolerance may be overwhelmed by the nonlinear accumulation of caffeine and other methylxanthines in the body when caffeine metabolism becomes saturable.