在空腹健康韩国男性志愿者中单剂量和多剂量口服后，右旋布洛芬控释和速释制剂的药代动力学比较。

Pharmacokinetic comparison of controlled- and immediate-release formulations of dexibuprofen after single and multiple oral doses in fasting healthy male Korean volunteers.

机构信息

Department of Clinical Pharmacology and Therapeutics, Asan Medical Center, Seoul, Korea.

出版信息

Clin Ther. 2011 Sep;33(9):1132-41. doi: 10.1016/j.clinthera.2011.07.019. Epub 2011 Aug 24.

DOI:10.1016/j.clinthera.2011.07.019

PMID:21864907

Abstract

BACKGROUND

Dexibuprofen is a pure S(+)-enantiomer product of racemic ibuprofen. A new extended-release form of dexibuprofen has recently been developed.

OBJECTIVE

We aimed to compare pharmacokinetic characteristics of controlled-release (CR) and immediate-release (IR) formulations of dexibuprofen after single and multiple oral doses in fasting healthy male Korean volunteers.

METHODS

Both single- and multiple-dose studies used an open-label, randomized, 2-way, crossover design. In the single-dose study, 24 subjects were administered a 600-mg CR or 300-mg IR formulation. In the multiple-dose study, 24 subjects were administered a 600-mg CR formulation q12h or 300-mg IR formulation q6h. Pharmacokinetic parameters of dexibuprofen were determined by noncompartmental analysis.

RESULTS

All formulations used in the single- and multiple-dose studies were well tolerated, and there were no severe adverse events. In the single-dose study, the mean (SD) AUC(0-t) was 155.60 (40.94) μg/h/mL for the CR formulation and 161.11 (37.50) μg/h/mL for the IR formulation; the mean (SD) C(max) values were 22.71 (6.64) and 23.77 (4.91) μg/mL, respectively; and the median T(max) values were 2.01 hours and 2.00 hours, respectively. The geometric mean ratios (90% CI) of the CR to IR formulations were 0.96 (0.92-1.00) for AUC(0-t) and 1.00 (0.87-1.14) for C(max). In the multiple-dose study, the mean (SD) AUC(0-τ) values for CR and IR were 129.70 (23.72) μg/h/mL and 150.04 (27.09) μg/h/mL, respectively; the mean (SD) C(max,ss) values were 24.51 (5.12) and 21.69 (5.21) μg/mL, respectively; and the median T(max.ss) values were 2.51 hours and 5.25 hours, respectively. The geometric mean ratios (90% CI) of the CR to IR formulations were 0.86 (0.81-0.91) for AUC(0-τ) and 1.13 (1.03-1.24) for C(max).

CONCLUSIONS

The pharmacokinetic parameters of single and multiple administrations of dexibuprofen did not differ for the IR and CR formulations in this small, selected group of healthy male Korean subjects. Both formulations were well tolerated.

摘要

背景

右旋布洛芬是消旋布洛芬的纯 S(+)-对映异构体产物。最近开发了一种新的右旋布洛芬控释制剂。

目的

我们旨在比较空腹健康韩国男性志愿者单次和多次口服控释（CR）和速释（IR）制剂的右旋布洛芬的药代动力学特征。

方法

单剂量和多剂量研究均采用开放标签、随机、2 向交叉设计。在单剂量研究中，24 名受试者分别给予 600mg CR 或 300mg IR 制剂。在多剂量研究中，24 名受试者分别给予 600mg CR 制剂 q12h 或 300mg IR 制剂 q6h。通过非房室分析测定右旋布洛芬的药代动力学参数。

结果

单剂量和多剂量研究中使用的所有制剂均耐受良好，无严重不良事件。在单剂量研究中，CR 制剂的 AUC（0-t）平均值（SD）为 155.60（40.94）μg/h/mL，IR 制剂为 161.11（37.50）μg/h/mL；C（max）值的平均值（SD）分别为 22.71（6.64）和 23.77（4.91）μg/mL；中位数 T（max）值分别为 2.01 小时和 2.00 小时。CR 与 IR 制剂的几何均数比值（90%CI）分别为 AUC（0-t）的 0.96（0.92-1.00）和 C（max）的 1.00（0.87-1.14）。在多剂量研究中，CR 和 IR 的 AUC（0-τ）平均值分别为 129.70（23.72）μg/h/mL 和 150.04（27.09）μg/h/mL；C（max，ss）平均值分别为 24.51（5.12）和 21.69（5.21）μg/mL；中位数 T（max，ss）值分别为 2.51 小时和 5.25 小时。CR 与 IR 制剂的几何均数比值（90%CI）分别为 AUC（0-τ）的 0.86（0.81-0.91）和 C（max）的 1.13（1.03-1.24）。