Pedroso P, Almeida S, Filipe A, Neves R I, Boudreault S, Jiménez C
Medical Department, Tecnimede S.A., Sintra, Portugal.
Drug Res (Stuttg). 2013 Sep;63(9):477-83. doi: 10.1055/s-0033-1347235. Epub 2013 Jun 18.
In order to assess the bioequivalence of 2 different formulations of montelukast, a pivotal trial for the montelukast 10 mg film-coated tablets formulation and a pivotal trial for the montelukast 5 mg chewable tablets formulation were conducted.For the 10 mg study, 34 healthy subjects were enrolled in a single centre, randomised, single-dose, open-label, 2-way crossover study, with a minimum washout period of 7 days, while for the 5 mg study, 42 healthy subjects were included in another study with a similar design. For both studies, plasma samples were collected up to 24 h post-dosing and drug levels were determined by reverse liquid chromatography and detected by tandem mass spectrometry detection.Pharmacokinetic parameters used for bioequivalence assessment, area under the concentration-time curve from time zero to time of last non-zero concentration (AUC0-t) and from time zero to infinity (AUC0-inf) and maximum observed concentration (Cmax), were determined from the drug concentration data using non-compartmental analysis.In the 10 mg study, the 90% confidence intervals obtained by analysis of variance were 99.62-120.51% for Cmax, 102.25-117.37% for AUC0-t and 101.96-116.67% for AUC0-inf, which were within the predefined acceptable range of 80.00-125.00%.In the 5 mg study, the 90% confidence intervals were 91.14-98.46% for Cmax, 93.02-98.42% for AUC0-t and 93.09-98.63% for AUC0-inf, which were within the predefined acceptable range of 80.00-125.00%.Bioequivalence between formulations was concluded both in terms of rate and extent of absorption for both strengths.
为评估孟鲁司特两种不同剂型的生物等效性，分别开展了孟鲁司特10毫克薄膜包衣片剂型的关键试验和孟鲁司特5毫克咀嚼片剂型的关键试验。在10毫克研究中，34名健康受试者参与了一项单中心、随机、单剂量、开放标签、双向交叉研究，最短洗脱期为7天；而在5毫克研究中，42名健康受试者纳入了另一项设计相似的研究。两项研究均在给药后24小时内采集血浆样本，药物水平通过反相液相色谱法测定，并通过串联质谱检测进行检测。用于生物等效性评估的药代动力学参数，从零时间到最后一个非零浓度时间的浓度-时间曲线下面积（AUC0-t）、从零时间到无穷大的浓度-时间曲线下面积（AUC0-inf）以及最大观测浓度（Cmax），使用非房室分析从药物浓度数据中确定。在10毫克研究中，通过方差分析获得的90%置信区间，Cmax为99.62 - 120.51%，AUC0-t为102.25 - 117.37%，AUC0-inf为101.96 - 116.67%，均在预先定义的80.00 - 125.00%可接受范围内。在5毫克研究中，90%置信区间，Cmax为91.14 - 98.46%，AUC0-t为93.02 - 98.42%，AUC0-inf为93.09 - 98.63%，也在预先定义的80.00 - 125.00%可接受范围内。两种强度的剂型在吸收速率和程度方面均得出生物等效的结论。
