Sourgens H, Steinbrede H, Verschoor J S, Bertola M A, Rayer B
University of Münster, Germany.
Int J Clin Pharmacol Ther. 2001 Feb;39(2):75-82. doi: 10.5414/cpp39075.
With amoxicillin/clavulanic acid Solutab tablet, a new tablet formulation of amoxicillin/clavulanic acid (500/125), was developed. The aim of the present study was to demonstrate bioequivalence between the new tablet formulation, taken as an intact tablet and after prior dispersal, versus the originator product viz. Augmentan film-coated tablet. The study was performed in 48 healthy volunteers, according to an open, single-dose three-period, crossover design. Blood samples were taken prior to each administration and at 10 time points after dosing. Plasma concentrations of amoxicillin and clavulanic acid were determined by validated high performance liquid chromatography with UV detection. With regard to amoxicillin, the results were within the preset bioequivalence range of 0.8 to 1.25 for the ratios of the primary parameters AUC(0-t) and Cmax. In terms of clavulanic acid the 90% confidence intervals of the ratios for AUC(0-t) and Cmax versus the reference lay outside the predefined bioequivalence range of 0.75 to 1.33. This result, however, was mainly due to the large variability of the reference formulation compared to the amoxicillin/clavulanic acid Solutab tablet. Based on statistical indications that 3/48 subjects with extremely low levels on the reference formulation could be regarded as "outliers" and after excluding these subjects' data from the statistical analysis, results for clavulanic acid were within the predefined bioequivalence range of 0.75 to 1.33. Overall, the amoxicillin/clavulanic acid Solutab tablet provided, in comparison to the reference tablet, less variable levels of clavulanic acid, thus giving more appropriate protection to the available amoxicillin. Thirteen adverse events were reported post dosing by 7 subjects. There were no differences in incidence of adverse events between amoxicillin/clavulanic acid Solutab tablet taken intact or dispersed and Augmentan.
研发出了阿莫西林/克拉维酸索拉塔布片，这是一种新型的阿莫西林/克拉维酸（500/125）片剂剂型。本研究的目的是证明该新型片剂剂型在完整服用及预先分散后与原研产品即奥格门汀薄膜包衣片之间的生物等效性。该研究在48名健康志愿者中按照开放、单剂量、三期交叉设计进行。在每次给药前及给药后10个时间点采集血样。采用经过验证的带紫外检测的高效液相色谱法测定血浆中阿莫西林和克拉维酸的浓度。对于阿莫西林，主要参数AUC(0-t)和Cmax的比值结果在预设的0.8至1.25生物等效性范围内。就克拉维酸而言，AUC(0-t)和Cmax与参比制剂的比值的90%置信区间超出了预先定义的0.75至1.33生物等效性范围。然而，这一结果主要是由于参比制剂与阿莫西林/克拉维酸索拉塔布片相比变异性较大。基于统计学表明参比制剂水平极低的3/48名受试者可被视为“异常值”，在将这些受试者的数据排除在统计分析之外后，克拉维酸的结果在预先定义的0.75至1.33生物等效性范围内。总体而言，与参比片剂相比，阿莫西林/克拉维酸索拉塔布片提供的克拉维酸水平变异性较小，从而能为现有的阿莫西林提供更合适的保护。7名受试者在给药后报告了13起不良事件。完整服用或分散服用的阿莫西林/克拉维酸索拉塔布片与奥格门汀之间不良事件的发生率没有差异。
