Spínola Ana Cristina Franco, Almeida Susana, Filipe Augusto, Tanguay Mario, Yritia Mercedes
Medical Department, Grupo Tecnimede, Prior Velho, Portugal.
Arzneimittelforschung. 2008;58(3):122-5.
This study was conducted in order to assess the bioequivalence of two tablet formulations containing 100 mg sildenafil (1-[4-ethoxy-3-(6,7-dihydro-1-,ethyl-7-oxo-3-propyl-1H-pyrazolo[4,3-d]pyrimidin-5-yl)phenylsulphonyl] -4-methyl piperazine, CAS 139755-83-2). Twenty-eight 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. Plasma samples were collected up to 18.0 h postdosing. Sildenafil levels were determined by reverse liquid chromatography coupled with tandem mass spectrometry detection (LC-MS/MS). Pharmacokinetic parameters used for bioequivalence assessment [area under the concentration-time curve from time zero to time of last non-zero concentration (AUC(last)) and maximum observed concentration (C(max)) were main evaluation criteria; however, the area under the concentration-time curve from time zero to infinity (AUC(inf)) was also analysed] were determined from the sildenafil concentration data using non-compartmental analysis. The 90% confidence intervals (obtained by analysis of variance, ANOVA) were 86.70-108.19 for C(max), 86.67-99.26 for AUC(last) and 87.19-99.82 for AUC(inf) within the predefined ranges. Bioequivalence between the two formulations was concluded both in terms of rate and extent of absorption.
本研究旨在评估两种含有100毫克西地那非（1-[4-乙氧基-3-(6,7-二氢-1-乙基-7-氧代-3-丙基-1H-吡唑并[4,3-d]嘧啶-5-基)苯基磺酰基]-4-甲基哌嗪，CAS 139755-83-2）的片剂制剂的生物等效性。28名健康受试者参与了一项单中心、随机、单剂量、开放标签的双向交叉研究，最短洗脱期为7天。给药后长达18.0小时采集血浆样本。西地那非水平通过反相液相色谱-串联质谱检测（LC-MS/MS）测定。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（AUC(last)）和最大观察浓度（C(max)）是主要评估标准；然而，也分析了从零时间到无穷大的浓度-时间曲线下面积（AUC(inf)）]使用非房室分析从西地那非浓度数据中确定。在预定义范围内，C(max)的90%置信区间（通过方差分析，ANOVA获得）为86.70-108.19，AUC(last)为86.67-99.26，AUC(inf)为87.19-99.82。两种制剂在吸收速率和程度方面均具有生物等效性。
