盐酸文拉法辛渗透泵型缓释片人体药动学特性

Study on pharmacokinetics of osmotic pump tablets of hydrochloride venlafaxine in Chinese healthy volunteers

目的比较餐后状态下两种盐酸文拉法辛缓释片在中国健康受试者体内药动学及生物等效性。方法本试验入组26例受试者,采用随机、开放、两周期、两序列、双交叉给药设计,单次口服受试或参比制剂(75 mg)后,运用LC-MS/MS测定血浆中文拉法辛(VEN)及其活性代谢产物O-去甲基文拉法辛(ODV)浓度,经PhoenixTM WinNonlin 6.4软件计算药动学参数,以VEN的药动学参数作为评价指标,ODV作为参考,进行生物等效性分析。结果餐后服用受试或参比制剂后,血浆VEN的Cmax分别为(58.50±19.47)和(60.14±22.18)μg·L^(-1),AUC0-t分别为(1074.1±526.7)和(1057.9±539.7)μg·h·L^(-1),AUC0-∞分别为(1084.7±536.8)和(1067.8±554.0)μg·h·L^(-1);ODV的Cmax分别为(101.63±29.64)和(101.45±31.62)μg·L^(-1),AUC0-t分别为(2694.0±834.5)和(2702.9±946.4)μg·h·L^(-1),AUC0-∞分别为(2753.9±885.5)和(2753.2±988.4)μg·h·L^(-1),VEN和ODV的Cmax,AUC0-t,AUC0-∞几何均数比值90%CI均在80.00%~125.00%等效区间内。结论餐后状态下,两制剂在中国健康受试者体内具有生物等效性。

Aim To evaluate the pharmacokinetics and bioequivalence of two osmotic pump tablets of hydrochloride venlafaxine in Chinese healthy volunteers.Methods The fed test each enrolled twenty-six Chinese healthy volunteers in a randomized-sequence,open-label,two-period crossover single-dose oral test and reference preparations of hydrochloride venlafaxine extended-release tablets.The plasma concentrations of venlafaxine and its active metabolites O-desmethylvenlafaxine were determined by a validated liquid chromatography-tandem mass spectrometry(LC-MS/MS)method,and the pharmacokinetic parameters and bioequivalence of the two tablets were analyzed using PhoenixTM WinNonlin 6.4 software.Results The pharmacokinetic parameters of venlafaxine after single dose for the test and reference tablets were as follows:Cmax(58.50±19.47)vs(60.14±22.18)μg·L^(-1),AUC0-t(1074.1±526.7)vs(1057.9±539.7)μg·h·L^(-1),AUC0-∞(1084.7±536.8)vs(1067.8±554.0)μg·h·L^(-1).The pharmacokinetic parameters of O-desmethylvenlafaxine were as follows:Cmax(101.63±29.64)vs(101.45±31.62)μg·L^(-1),AUC0-t(2694.0±834.5)vs(2702.9±946.4)μg·h·L^(-1),AUC0-∞(2753.9±885.5)vs(2753.2±988.4)μg·h·L^(-1).The 90%confidence intervals of the geometric mean ratios of Cmax,AUC0-t,AUC0-∞for the test preparation and the reference preparation were all within the equivalent interval of 80.00%-125.00%.Conclusion The test and reference preparations of hydrochloride venlafaxine extended-release tablets are bioequivalent in Chinese healthy volunteers under fed conditions.