The clinical pharmacokinetics of osmotic pump controlled release tablets of terazosin hydrochloride in healthy volunteers  

盐酸特拉唑嗪口服渗透泵控释片人体药物动力学研究(英文)

作　　者：马廷升[1] 李高[2] 杨光忠[3] 刘志华[1] 朱兰寸[1] 

机构地区：[1]怀化医学高等专科学校药学系,湖南怀化418000 [2]华中科技大学同济医学院药学院,湖北武汉430030 [3]中南民族大学药学院,湖北武汉430074

出　　处：《Journal of Chinese Pharmaceutical Sciences》2011年第3期253-258,共6页中国药学（英文版）

基　　金：Hunan Department of Education(Grant No.07C048).

摘　　要：The clinical pharmacokinetics of osmotic pump controlled release tablets of terazosin hydrochloride in healthy volunteers was studied.A sensitive and rapid HPLC method was used to determine the terazosin plasma concentrations,and single and multiple doses of terazosin hydrochloride regular tablets（reference tablets）and osmotic pump controlled release tablets were orally administrated in randomized crossover design.The results showed that the C_（max）of the reference tablets after single oral dose（（120.56±23.15）ng/mL）in 20 healthy volunteers was significantly higher than that of controlled release tablets （（95.27±16.35）ng/mL）.The T_（max）of the controlled release tablets（（2.65±0.82）h）was significantly longer than that of reference tablets（（1.27±0.61）h）（P0.05）.The relative bioavailability of the controlled release tablets was found to be（105.85±6.12）%. The multiple oral dose pharmacokinetic parameters of the regular tablets and controlled release tablets were as follows：AUC_（SS） were（1275.17±175.35）and（1382.65±205.31）ng·h/mL respectively,C_（max）were（128.15±22.37）and（98.57±18.16）ng/mL respectively,T_（max）were（1.35±0.71）and（2.76±0.85）h respectively,C_（av）were（53.13±9.12）and（57.61±9.25）ng/mL respectively, and DF were（2.25±0.26）%and（1.62±0.25）%respectively.The relative bioavailability of the controlled release tablets to the reference tablets was（108.43±6.26）%.The controlled release tablet of terazosin hydrochloride was bioequivalent to the reference tablet.The controlled release tablet exhibited a sustained-release property with a significantly longer T_（max）and lower C_（max）.本研究进行了盐酸特拉唑嗪口服渗透泵控释片在健康人体内的药物动力学分析。运用随机交叉实验设计,20名健康受试者单剂量、多剂量口服受试制剂、参比制剂,采用HPLC法测定血浆中盐酸特拉唑嗪的浓度,使用3P97软件计算药物动力学参数。单剂量口服控释片、普通片各4 mg后,普通片的C_(max)(120.56±23.15)ng/mL明显高于控释片的C_(max)(95.27±16.35)ng/mL。控释片口服给药后的T_(max)为(2.65±0.82)h,较普通片T_(max)(1.27±0.61)h延迟,有显著性差异(P<0.05),其相对生物利用度为(105.85±6.12)%。受试者多剂量口服普通片与控释片后药物动力学参数稳态时曲线下面积(AUC_(ss))分别为(1275.17±175.35)、(1382.65±205.31)ng·h/mL;C_(max)分别为(128.15±22.37)、(98.57±18.16)ng/mL;T_(max)分别为(1.35±0.71)、(2.76±0.85)h;平均稳态血药浓度(C_(av))分别为(53.13±9.12)、(57.61±9.25)ng/mL;血药浓度波动度(DF)分别为(2.25±0.26)%和(1.62±0.25)%,其相对生物利用度为(108.43±6.26)%。经统计学检验表明,这两种制剂的AUC_(0-48 h)、AUC_(0-∞)具有生物等效性,普通片与控释片口服时吸收程度等效,吸收速度不等效。控释片的达峰时间明显滞后普通制剂,该控释片显示出控释特征。

关 键 词：Terazosin hydrochloride Osmotic pump system Controlled release tablets PHARMACOKINETICS BIOEQUIVALENCE 

分 类 号：R969.1[医药卫生—药理学]