Hussein Rajaa, Lockyer Marilyn, Yusuf Ahmed, Al Gaai Eman, Abdelgaleel Abdelraheem, Hammami Muhammad M
Centre for Clinical Research, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia.
Arzneimittelforschung. 2007;57(5):269-73. doi: 10.1055/s-0031-1296617.
A randomized, single-dose, crossover study was conducted to assess the bioavailability of two domperidone (CAS 57808-66-9) tablet formulations, Domperidone (test) and a commercially available original preparation (reference) under fasting conditions. A 10 mg dose of each formulation was administered to 36 healthy male volunteers with a one-week washout period, 17 blood samples were collected over 48 h, plasma concentrations of domperidone were analyzed by a locally validated LC-MS-MS assay, and the pharmacokinetic parameters were determined by the standard non-compartmental method. Mean +/- SD maximum concentration (C(max)), time to reach maximum concentration (T(max)), areas under the curve (AUC(0 --> t and AUC(0 --> infininty)), and elimination constant (K(el)) were 17.13 +/- 9.62 and 17.67 +/- 7.97 ng/ml, 0.87 +/- 0.58, and 0.89 +/- 0.33 h, 73.12 +/- 43.37 and 71.45 +/- 35.41 ng x h/ml, 90.32 +/- 48.55 and 87.08 +/- 40.29 ng x h/ml, and 0.069 +/- 0.046 and 0.068 +/- 0.048 h(-1) for the test and reference formulation, respectively. The parametric 90% confidence intervals on the mean difference between log-transformed values of the two formulations were within the acceptable bioequivalence range for AUC(0 --> t) (87.84% to 109.60%), AUC(0 --> infinity) (89.05% to 111.67%) and C(max) (83.28% to 107.50%). ANOVA revealed significant subject's effect for AU4C(0 --> t), AUC((0 -->infinity), C(max), and t1/2 with a ratio of the inter-subject to intra-subject coefficient of variation of 2.10, 1.55, 1.10, and 1.02, respectively. The results indicate that the two formulations are equivalent in relation to the extent and rate of absorption and confirm the previously reported marked intra-individual variations in the pharmacokinetics of domperidone.
进行了一项随机、单剂量、交叉研究，以评估两种多潘立酮（化学物质登记号57808 - 66 - 9）片剂制剂（多潘立酮（试验制剂）和市售原研制剂（参比制剂））在空腹条件下的生物利用度。向36名健康男性志愿者分别给予10 mg剂量的每种制剂，洗脱期为一周，在48小时内采集17份血样，采用本地验证的液相色谱 - 串联质谱法分析多潘立酮的血浆浓度，并通过标准非房室方法确定药代动力学参数。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→∞)）以及消除常数（K(el)）分别为17.13±9.62和17.67±7.97 ng/ml、0.87±0.58和0.89±0.33小时、73.12±43.37和71.45±35.41 ng·h/ml、90.32±48.55和87.08±40.29 ng·h/ml以及0.069±0.046和0.068±0.048 h⁻¹。两种制剂对数转换值的均值差异的参数90%置信区间在AUC(0→t)（87.84%至109.60%）、AUC(0→∞)（89.05%至111.67%）和C(max)（83.28%至107.50%）的可接受生物等效性范围内。方差分析显示，对于AU4C(0→t)、AUC((0→∞)、C(max)和t1/2，受试者效应显著，受试者间与受试者内变异系数之比分别为l02.10、1.55、1.10和1.02。结果表明，两种制剂在吸收程度和吸收速率方面相当，并证实了先前报道的多潘立酮药代动力学存在明显的个体内差异。
