Al Hawari Samar, AlGaai Eman, Yusuf Ahmed, Abdelgaleel Abdelraheem, Hammami Muhammad M
Centre for Clinical Research, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia.
Arzneimittelforschung. 2007;57(4):192-5. doi: 10.1055/s-0031-1296605.
A randomized single-dose cross-over study was conducted on 24 healthy male volunteers to compare the bioavailability of two metformin (CAS 657-24-9) tablet formulations, Emiphage (test) and a commercially available original preparation (reference). A dose of 850 mg was administered after an overnight fast with a washout period of seven days. Eighteen blood samples were collected over 32 h. Metformin concentrations in deproteinized serum were determined by a locally validated High Performance Liquid Chromatographic (HPLC) assay, and pharmacokinetic parameters were analyzed by the standard non-compartmental method. Mean +/- SD maximum concentration (C(max)), time to reach maximum concentration (T(max)), area under the curve (AUC(0 --> t) and AUC(0 --> infinity)), and elimination half-life (t(1/2)) were 1.73 +/- 0.54 and 1.86 +/- 0.67 microg/ml, 2.6 +/- 1.2 and 2.0 +/- 1.0 h, 10.72 +/- 3.93 and 10.82 +/- 3.72 microg x h/ml, 11.53 - 4.14 and 11.6 +/- 3.84 microg x h/ml, and 3.1 +/- 0.7 and 3.1 +/- 0.9 h for the test and reference formulation, respectively. The parametric 90% confidence intervals on the mean of the difference (test - reference) between log-transformed values of the two formulations were 82.92% to 98.78%, 85.95% to 101.47%, and 77.82% to 100.4% for AUC(0 --> t), AUC(0 --> infinity), and C(max), respectively. The results indicate that the two formulations can be considered equivalent in the extent of absorption under fasting conditions.
对24名健康男性志愿者进行了一项随机单剂量交叉研究，以比较两种二甲双胍（CAS 657-24-9）片剂制剂Emiphage（试验制剂）和市售原研制剂（参比制剂）的生物利用度。禁食过夜后给予850 mg剂量，洗脱期为7天。在32小时内采集18份血样。采用经本地验证的高效液相色谱（HPLC）法测定去蛋白血清中的二甲双胍浓度，并采用标准的非房室模型方法分析药代动力学参数。试验制剂和参比制剂的平均±标准差最大浓度（C(max)）、达峰时间（T(max)）、曲线下面积（AUC(0→t)和AUC(0→∞)）以及消除半衰期（t(1/2)）分别为1.73±0.54和1.86±0.67μg/ml、2.6±1.2和2.0±1.0小时、10.72±3.93和10.82±3.72μg·小时/ml、11.53 - 4.14和11.6±3.84μg·小时/ml以及3.1±0.7和3.1±0.9小时。两种制剂对数转换值之间差异均值（试验制剂 - 参比制剂）的参数90%置信区间，AUC(0→t)、AUC(0→∞)和C(max)分别为82.92%至98.78%、85.95%至101.47%和77.82%至100.4%。结果表明，在禁食条件下，两种制剂在吸收程度上可被视为等效。
