Im Yong-Jin, Jeon Ji-Young, Kim Eun-Young, Kim Yunjeong, Oh Dong-Joon, Yoo Ji-Seok, Shin Dae-Hee, Chae Soo-Wan, Kim Min-Gul
Clinical Trial Center and Biomedical Research Institute, Chonbuk National University Hospital, Jeonju, Republic of Korea.
Yungjin Pharmaceutical Co, Ltd, Gangdong-gu, Seoul, Republic of Korea.
Clin Ther. 2015 Feb 1;37(2):376-89. doi: 10.1016/j.clinthera.2014.12.007. Epub 2015 Jan 22.
To provide consistent pain relief and improve convenient sustained release (SR), a fixed-dose combination tramadol/acetaminophen tablet was formulated. This study aimed to evaluate the pharmacokinetic profiles of an SR 75-mg tramadol/650-mg acetaminophen formulation after a single dose compared with an immediate release (IR) 37.5-mg tramadol/325-mg acetaminophen formulation after 2 doses and at steady state and to assess the effect of food on the pharmacokinetic SR formulation profile after a single dose.
Two clinical trials were conducted: (1) an open-label, randomized, 3-period, 3-treatment, crossover study to assess the pharmacokinetic SR (one 75-mg tramadol/650-mg acetaminophen combination tablet) formulation profiles after a single dose and IR (one 37.5-mg tramadol/325-mg acetaminophen combination tablet q6h for 2 doses) formulation profiles after 2 doses and the effect of food intake on healthy male subjects and (2) an open, randomized, 2-period, 2-treatment multiple dose crossover study to evaluate the steady-state pharmacokinetic SR and IR formulation profiles. Safety assessments were performed.
Forty-three subjects completed each study protocol. The SR combination tramadol/acetaminophen formulation was clinically and statistically equivalent to the IR combination formulation in the fasting state. When tramadol and acetaminophen tablets were administered with food, the time to peak plasma concentrations and the tramadol/acetaminophen absorption were unaffected. There was no serious adverse event reported.
The SR combination tramadol/acetaminophen tablet exhibited similar exposure and absorption rates compared with those of the IR formulation of tramadol, O-desmethyltramadol, and acetaminophen. The SR formulation may be more convenient for patients and has the potential to enhance compliance and pain control. ClinicalTrials.gov identifier: NCT01880125.
为提供持续一致的疼痛缓解并改善方便的缓释（SR）效果，制备了固定剂量的曲马多/对乙酰氨基酚复方片剂。本研究旨在评估单剂量后75毫克曲马多/650毫克对乙酰氨基酚缓释制剂的药代动力学特征，并与两剂后及稳态时37.5毫克曲马多/325毫克对乙酰氨基酚速释（IR）制剂进行比较，同时评估食物对单剂量后缓释制剂药代动力学特征的影响。
进行了两项临床试验：（1）一项开放标签、随机、3期、3治疗组的交叉研究，以评估单剂量后缓释（一片75毫克曲马多/650毫克对乙酰氨基酚复方片剂）制剂的药代动力学特征以及两剂后速释（一片37.5毫克曲马多/325毫克对乙酰氨基酚复方片剂，每6小时服用一剂，共两剂）制剂的药代动力学特征，以及食物摄入对健康男性受试者的影响；（2）一项开放、随机、2期、2治疗组的多剂量交叉研究，以评估稳态时缓释和速释制剂的药代动力学特征。进行了安全性评估。
43名受试者完成了每项研究方案。在禁食状态下，曲马多/对乙酰氨基酚缓释复方制剂在临床和统计学上与速释复方制剂等效。当曲马多和对乙酰氨基酚片剂与食物一起服用时，血浆浓度达峰时间以及曲马多/对乙酰氨基酚的吸收不受影响。未报告严重不良事件。
与曲马多、O-去甲基曲马多和对乙酰氨基酚的速释制剂相比，曲马多/对乙酰氨基酚缓释复方片剂表现出相似的暴露量和吸收率。缓释制剂对患者可能更方便，并且有可能提高依从性和疼痛控制效果。ClinicalTrials.gov标识符：NCT01880125。
