咖啡因对乙酰水杨酸-对乙酰氨基酚复方制剂生物利用度和药代动力学的影响：一项 I 期研究的结果。
Effect of Caffeine on the Bioavailability and Pharmacokinetics of an Acetylsalicylic Acid-Paracetamol Combination: Results of a Phase I Study.
机构信息
Medical Affairs CHC, Sanofi-Aventis Deutschland GmbH, Industriepark Höchst, Frankfurt am Main, Germany.
出版信息
Adv Ther. 2019 Mar;36(3):597-607. doi: 10.1007/s12325-019-0891-5. Epub 2019 Feb 13.
INTRODUCTION
Caffeine is used as an adjuvant in analgesic combinations to enhance their efficacy. The present study aimed to determine the effect of caffeine on the pharmacokinetics of acetylsalicylic acid (ASA) and paracetamol when used as a fixed-dose ASA/paracetamol/caffeine combination.
METHODS
In this single-centre, two-way, cross-over phase I study, volunteers fasted overnight (≥ 12 h) and randomly received single oral doses of 250 mg ASA/200 mg paracetamol (reference) or 250 mg ASA/200 mg paracetamol/50 mg caffeine (test). Blood samples were collected before and up to 24 h after dosing. The primary end points were the area under the concentration-time curve from zero to infinity (AUC) and maximum plasma concentration (C) for ASA, salicylic acid (SA) and paracetamol from the two combinations. The main secondary end points were AUC and C of caffeine and time to reach C (t) of all drugs.
RESULTS
Eighteen healthy male volunteers (32.5 ± 10.5 years) participated in the study. The geometric means of C for ASA, SA and paracetamol were similar in the test (3.71, 15.8 and 2.42 µg/ml, respectively) and reference groups (3.89, 15.8, 2.42 µg/ml, respectively). The geometric mean of AUC for ASA, SA and paracetamol from the test combination was 2.86, 60.5 and 7.68 µg h/ml, respectively, and that for the reference was 2.96, 59.1 and 7.77 µg h/ml, respectively. The medians of t for ASA, SA and paracetamol were similar between the two groups. The point estimates for the ratios of AUC and C for test versus reference regarding ASA, SA and paracetamol were within the predefined equivalence limits. The two treatments were well tolerated.
CONCLUSION
Caffeine did not affect the pharmacokinetics of ASA and paracetamol when used as an adjuvant in ASA/paracetamol fixed-dose combination under fasting conditions, suggesting that caffeine enhances the analgesic efficacy of these drugs by pharmacodynamic rather than pharmacokinetic interactions.
FUNDING
Sanofi-Aventis Deutschland GmbH.
简介
咖啡因作为一种佐剂添加到镇痛组合药物中以增强其疗效。本研究旨在确定咖啡因对乙酰水杨酸（ASA）和扑热息痛的药代动力学的影响，这两种药物以固定剂量 ASA/扑热息痛/咖啡因组合使用。
方法
在这项单中心、双交叉、I 期研究中，志愿者禁食过夜（≥12 小时），并随机接受单剂量 250mg ASA/200mg 扑热息痛（参比）或 250mg ASA/200mg 扑热息痛/50mg 咖啡因（试验）。在给药前和给药后 24 小时内采集血样。主要终点是 ASA、水杨酸（SA）和扑热息痛的零到无穷大（AUC）和最大血浆浓度（C）的曲线下面积（AUC）。主要次要终点是咖啡因的 AUC 和 C 以及所有药物达到 C（t）的时间。
结果
18 名健康男性志愿者（32.5±10.5 岁）参加了这项研究。试验组（分别为 3.71、15.8 和 2.42μg/ml）和参比组（分别为 3.89、15.8 和 2.42μg/ml）中 ASA、SA 和扑热息痛的 C 的几何平均值相似。试验组合中 ASA、SA 和扑热息痛的 AUC 几何平均值分别为 2.86、60.5 和 7.68μg·h/ml，参比组分别为 2.96、59.1 和 7.77μg·h/ml。ASA、SA 和扑热息痛的 t 的中位数在两组之间相似。ASA、SA 和扑热息痛的 AUC 和 C 的试验与参比比值的点估计值在预定的等效限度内。两种治疗方法均耐受良好。
结论
在禁食条件下，咖啡因作为 ASA/扑热息痛固定剂量组合中的佐剂使用时，不会影响 ASA 和扑热息痛的药代动力学，这表明咖啡因通过药效而非药代动力学相互作用增强了这些药物的镇痛效果。
资助
赛诺菲-安万特德国有限公司。
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