Introduction
A fixed-dose combination (FDC) of ibuprofen and acetaminophen has been developed that provides greater analgesic efficacy than either agent alone at the same doses without increasing the risk for adverse events.

Methods
We report three clinical phase I studies designed to assess the pharmacokinetics (PK) of the FDC of ibuprofen/acetaminophen 250/500 mg (administered as two tablets of ibuprofen 125 mg/acetaminophen 250 mg) in comparison with its individual components administered alone or together, and to determine the effect of food on the PK of the FDC. Two studies in healthy adults aged 18–55 years used a crossover design in which subjects received a single dose of each treatment with a 2-day washout period between each. In the third study, the bioavailability of ibuprofen and acetaminophen from a single oral dose of the FDC was assessed in healthy adolescents aged 12–17 years, inclusive.

Results
A total of 35 and 46 subjects were enrolled in the two adult studies, respectively, and 21 were enrolled in the adolescent study. Ibuprofen and acetaminophen in the FDC were bioequivalent to the monocomponents administered alone or together. With food, the maximum concentration ( C _max) for ibuprofen and acetaminophen from the FDC was reduced by 36% and 37%, respectively, and time to C _max (i.e. t _max) was delayed. Overall drug exposure to ibuprofen or acetaminophen in the fed versus fasted states was similar. In adolescents, overall exposure to acetaminophen and ibuprofen was comparable with that in adults, with a slightly higher overall exposure to ibuprofen. Exposure to acetaminophen and ibuprofen in adolescents aged 12–14 years was slightly higher versus those aged 15–17 years. Adverse events were similar across all treatment groups.

Conclusions
The FDC of ibuprofen/acetaminophen 250/500 mg has a PK profile similar to its monocomponent constituents when administered separately or coadministered, indicating no drug–drug interactions and no formulation effects. Similar to previous findings for the individual components, the rates of absorption of ibuprofen and acetaminophen from the FDC were slightly delayed in the presence of food. Overall, adolescents had similar exposures to acetaminophen and ibuprofen as adults, while younger adolescents had slightly greater exposure than older adolescents, probably due to their smaller body size. The FDC was generally well tolerated.



中文翻译：

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健康成人和青少年人群中布洛芬和对乙酰氨基酚固定剂量联合用药的第一阶段药代动力学研究

引言
已经开发出布洛芬和对乙酰氨基酚的固定剂量组合（FDC），与相同剂量下单独使用任何一种药物相比，其止痛效果都更高，且不会增加发生不良事件的风险。

方法
我们报告了三项临床I期研究，旨在评估布洛芬/对乙酰氨基酚250/500毫克（以两片布洛芬125毫克/对乙酰氨基酚250毫克给药）与其单独或一起给药的FDC的药代动力学（PK） ，并确定食物对FDC PK的影响。两项针对18-55岁健康成年人的研究采用了交叉设计，受试者接受单次剂量的每种治疗，每次间隔2天。在第三项研究中，对12-17岁（含）的健康青少年进行了单次口服FDC对布洛芬和对乙酰氨基酚的生物利用度的评估。

结果
两项成人研究分别招募了35名和46名受试者，而青少年研究招募了21名受试者。FDC中的布洛芬和对乙酰氨基酚与单独或共同给药的单组分生物等效。对于食物，来自FDC的布洛芬和对乙酰氨基酚的最大浓度（ C _max）分别降低了36％和37％，并且达到 C _max的时间 （即 t _max） 被延迟。在进食与禁食状态下，布洛芬或对乙酰氨基酚的总体药物暴露相似。在青少年中，对乙酰氨基酚和布洛芬的总体暴露量与成人相当，但布洛芬的总体暴露量略高。在12-14岁的青少年中，对乙酰氨基酚和布洛芬的暴露水平比15-17岁的青少年略高。在所有治疗组中，不良事件均相似。

结论
布洛芬/对乙酰氨基酚250/500 mg的FDC单独或共同施用时，其PK谱与其单组分相似，表明没有药物相互作用，也没有制剂作用。与以前对单个成分的发现相似，在有食物的情况下，布洛芬和对乙酰氨基酚从FDC的吸收速率略有延迟。总体而言，青少年对乙酰氨基酚和布洛芬的暴露量与成人相似，而年轻青少年的暴露量比年龄较大的青少年略大，这可能是由于他们的体型较小。FDC通常被很好地容忍。