盐酸文拉法辛缓释胶囊在中国健康受试者体内的药代动力学及生物等效性研究  

Pharmacokinetics and bioequivalence of venlafaxine hydrochloride sustained-release capsules in Chinese healthy volunteers

作　　者：许浩云[1] 刘剑锋[2] 伊金玲 柳云玲 林游游 熊文刚 谢黎崖[1] XU Hao-yun;LIU Jian-feng;YI Jin-ling;LIU Yun-ling;LIN You-you;XIONG Wen-gang;XIE Li-ya(Drug Clinical Trial Institution,The First Affiliated Hospital of Xiamen University,Xiamen 361003,Fujian Province,China;BE/Phase I Clinical Research Center,The First Affiliated Hospital of Xiamen University,Xiamen 361003,Fujian Province,China;AccuBE PharmaTech Co.,LTD,Xiamen 361026,Fujian Province,China)

机构地区：[1]厦门大学附属第一医院药物临床试验机构,福建厦门361003 [2]厦门大学附属第一医院BE/I期临床研究中心,福建厦门361003 [3]莱必宜科技(厦门)有限公司,福建厦门361026

出　　处：《中国临床药理学杂志》2023年第2期271-275,共5页The Chinese Journal of Clinical Pharmacology

摘　　要：目的 研究餐后条件下文拉法辛及其代谢产物O-去甲文拉法辛在健康人体的药代动力学特性,并评价其生物等效性。方法 用随机、开放、双序列、两周期交叉试验设计,28例健康受试者单剂量餐后单次口服受试药物和参比药物,清洗期为7 d;用高效液相色谱-串联质谱法测定健康受试者血浆中文拉法辛及其代谢产物O-去甲文拉法辛的浓度,用WinNonlin 6.4软件计算各自的药代动力学参数,评价两制剂的生物等效性。结果 餐后单次给药后文拉法辛的主要药代动力学参数:受试制剂和参比制剂的C_(max)分别为(123.23±44.47)和(118.93±44.53)ng·mL^(-1),t_(_(max))分别为5.00(4.00,6.00)和5.00(3.00,11.00)h,t1/2分别为(9.39±2.66)和(9.90±2.62)h, AUC_(0-t)分别为(1 969.42±1 063.97)和(1 964.42±1 203.89)ng·mL^(-1)·h, AUC_(0-∞)分别为(2 104.89±1287.14)和(2 124.22±1 459.73)ng·mL^(-1)·h。代谢物O-去甲文拉法辛的主要药代动力学参数:参比制剂和受试制剂的C_(max)分别为(176.75±54.76)和(176.02±47.30)ng·mL^(-1),t_(max)分别为10.00(6.00,13.00)和10.00(5.00,13.00)h,t1/2分别为(12.80±2.52)和(13.06±2.10)h, AUC_(0-t)分别为(4600.54±1246.00)和(4 582.65±1 035.04)ng·mL^(-1)·h, AUC_(0-∞)分别为(5 152.36±1 403.51)和(5 286.86±1 161.96)ng·mL^(-1)·h。单次口服文拉法辛受试药物和参比药物,血浆中文拉法辛的C_(max)、AUC_(0-t)和AUC_(0-∞)的几何均值比90%置信区间分别为98.66%~109.99%,97.61%~107.67%和96.70%~106.94%。结论 餐后给药条件下,文拉法辛受试药物和参比制剂有生物等效性。Objective To study the pharmacokinetic(PK) characteristic and evaluate the bioequivalence of venlafaxine (VEN) and its metabolite O-desmethylvenlafaxine (ODV) in healthy human plasma under fed condition between two formulations of venlafaxine.Methods Randomized,open,two-cycle,two-sequence,double-crossover design was used.Twenty-eight healthy volunteers were recruited,and given a single oral dose of test and reference drugs under fed conditions,and the washout period was 7 d,and the concentration of venlafaxine and O-desmethylvenlafaxine in plasma were determined by HPLC-MS/MS platform.The pharmacokinetic parameters were calculated by WinNonlin6.4,and the bioequivalence was evaluated in the study.Results The main pharmacokinetic parameters of venlafaxine test and reference formulations were as follows:C_(max)were (123.23±44.47) and (118.93±44.53) ng·mL^(-1);t_(max)were 5.00 (4.00,6.00) and 5.00 (3.00,11.00) h,t1/2were (9.39±2.66) and (9.90±2.62) h;AUC_(0-t)were(1 969.42±1 063.97) and (1 964.42±1 203.89) ng·mL^(-1)·h,AUC_(0-∞)were (2 104.89±1 287.14) and(2 124.22±1 459.73) ng·mL^(-1)·h.The main pharmacokinetic parameters of metabolite O-desmethylvenlafaxine reference and test formulations were as follows:C_(max)were (176.75±54.76) and (176.02±47.30) ng·mL^(-1);t_(max)were 10.00 (6.00,13.00) and 10.00 (5.00,13.00) h;t1/2were (12.80±2.52) and (13.06±2.10) h;AUC_(0-t)were (4 600.54±1 246.00) and (4 582.65±1 035.04) ng·mL^(-1)·h;AUC_(0-∞)were (5 152.36±1 403.51) and(5 286.86±1 161.96) ng·mL^(-1)·h.The 90%CI of C_(max),AUC_(0-t)and AUC_(0-∞)of single oral venlafaxine test and reference drugs were 98.66%-109.99%,97.61%-107.67%,and 96.70%-106.94%under fed condition,respectively.Conclusion Under fed conditions,these two formulations of venlafaxine hydrochloride sustainedrelease capsules are bioequivalent in Chinese healthy subjects.

关 键 词：文拉法辛 O-去甲文拉法辛 液相串联质谱法 药代动力学 生物等效性 

分 类 号：R971[医药卫生—药品]