在韩国健康受试者中比较新型每日一次控释制剂醋氯芬酸与普通制剂醋氯芬酸及食物影响的药代动力学：一项随机、开放标签、三周期、交叉、单中心研究。
Pharmacokinetics of a new once-daily controlled-release formulation of aceclofenac in Korean healthy subjects compared with immediate-release aceclofenac and the effect of food: a randomized, open-label, three-period, crossover, single-centre study.
机构信息
College of Pharmacy, The Catholic University of Korea, Bucheon, South Korea.
出版信息
Clin Drug Investig. 2012 Feb 1;32(2):111-9. doi: 10.2165/11596530-000000000-00000.
BACKGROUND
A new controlled-release formulation of aceclofenac 200 mg (Clanza CR®) developed by Korea United Pharm., Inc., South Korea, for once-daily (od) dosing provides biphasic aceclofenac release consisting of immediate release of 85 mg followed by sustained release of 115 mg. Food has been known to affect the rate and extent of absorption of several drugs, in both immediate-release and controlled-release formulations.
OBJECTIVE
The aim of this study was to evaluate the relative bioavailability of a new controlled-release formulation of aceclofenac (200 mg od; Clanza CR®) in comparison with immediate-release aceclofenac (100 mg twice daily [bid], Airtal®) and to assess the effect of food on the pharmacokinetics of the new controlled-release aceclofenac formulation.
METHODS
This study was designed as a randomized, open-label, three treatment-period, crossover, single-centre study with a 1-week washout in 41 healthy adults. The three treatments consisted of immediate-release aceclofenac 100 mg bid administered under fasting conditions; controlled-release aceclofenac 200 mg od administered under fasting conditions; and controlled-release aceclofenac 200 mg od administered immediately after a standardized high-fat breakfast. Plasma concentrations of aceclofenac were determined using a high-performance liquid chromatography method.
RESULTS
In the fasted state, the 90% confidence intervals (CIs) of the least squares geometric mean ratios (GMRs) for the area under the plasma concentration-time curve from time zero to 24 hours (AUC(24)) and the peak plasma concentration (C(max)) of aceclofenac for the controlled-release and immediate-release formulations of aceclofenac were all within the bioequivalence criteria range of 0.8-1.25. The 90% CIs of the GMRs for the AUC(24) and C(max) of aceclofenac for the controlled-release formulation of aceclofenac in the fed and fasted states were also within the bioequivalence range. Both aceclofenac formulations were well tolerated in all subjects, and no serious adverse effects were observed.
CONCLUSION
The results demonstrate that controlled-release aceclofenac 200 mg is equivalent to immediate-release aceclofenac 100 mg when administered at the same total daily dose. Additionally, the bioavailability of controlled-release aceclofenac was not affected by high-fat foods.
背景
由韩国 United Pharm.，Inc. 研发的一种新的醋氯芬酸控释制剂（Clanza CR®），剂量为 200mg，每天一次（od），可实现双相醋氯芬酸释放，即 85mg 的即刻释放和 115mg 的持续释放。众所周知，食物会影响许多药物（包括即释制剂和控释制剂）的吸收速度和程度。
目的
本研究旨在评估一种新的醋氯芬酸控释制剂（200mg od；Clanza CR®）与醋氯芬酸即释制剂（100mg 每日两次[bid]，Airtal®）的相对生物利用度，并评估食物对新控释醋氯芬酸制剂药代动力学的影响。
方法
这是一项在 41 名健康成年人中进行的、设计为随机、开放标签、三治疗期、交叉、单中心研究，每个治疗期之间有 1 周洗脱期。三种治疗方案分别为：空腹条件下给予醋氯芬酸即释制剂 100mg bid；空腹条件下给予控释醋氯芬酸 200mg od；以及在标准化高脂肪早餐后立即给予控释醋氯芬酸 200mg od。采用高效液相色谱法测定醋氯芬酸的血浆浓度。
结果
在禁食状态下，控释和即释醋氯芬酸制剂的 AUC（24）和 Cmax 的最小二乘几何均数比值（GMR）的 90%置信区间（CI）均在 0.8-1.25 的生物等效性标准范围内。控释制剂在进食和禁食状态下的 AUC（24）和 Cmax 的 GMR 的 90%CI 也在生物等效范围内。所有受试者均耐受良好，未观察到严重不良事件。
结论
结果表明，控释醋氯芬酸 200mg 与即释醋氯芬酸 100mg 以相同的日总剂量给药时具有生物等效性。此外，高脂肪食物不会影响控释醋氯芬酸的生物利用度。
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