盐酸阿呋唑嗪缓释胶囊在Beagle犬体内的药动学与生物等效性研究  

Pharmacokinetics and Relative Bioavailability of Sustained-Release Alfzosin Hydrochloride Capsules in Healthy Beagle Dogs

作　　者：刘雪英[1] 王庆伟[2] 梅其炳[2] 李小强[2] 冯娟[2] 张生勇[1] 

机构地区：[1]第四军医大学药学系药物化学教研室,西安710032 [2]第四军医大学药理教研室,西安710032

出　　处：《中国药学杂志》2007年第6期466-469,共4页Chinese Pharmaceutical Journal

摘　　要：目的研究盐酸阿呋唑嗪缓释胶囊在Beagle犬体内的药动学与相对生物利用度。方法用高效液相色谱法测定了6条健康Beagle犬口服盐酸阿呋唑嗪缓释胶囊（受试制剂）和阿呋唑嗪普通片（参比制剂）后不同时间点血浆中阿呋唑嗪的浓度，绘制血药浓度-时间曲线，计算药动学参数及相对生物利用度。结果受试犬口服盐酸阿呋唑嗪20mg的受试制剂和参比制剂后，血浆中阿呋唑嗪的tmax分别为（1．42±0．49）和（0．79±0．19）h；ρmax分别为（323．92±70．82）和（508．31±120．62）μg·L^-1；用梯形法计算，AUC0-4分别为（1082．99±290．75）和（1174．56±336．31）μg·h·L^-1。以AUC计算，与参比制剂相比，受试制剂中阿呋唑嗪的相对生物利用度平均为（93．26±14．94）％。将AUC0-t对数转换后进行方差分析，结果表明，受试制剂与参比制剂相比，除个体间外，周期间与制剂间无显著性差异（P〉0．05），受试制剂AUC0-t的90％置信区间为参比制剂的82．5％～108．2％。结论盐酸阿呋唑嗪缓释胶囊与普通片相比，在犬体内有更长的作用时间，相对生物利用度接近。OBJECTIVE To study the pharmacokinetics and relative bioavailability of the sustained-release alfuzosin hydrochloride capsules in healthy Beagle dogs . METHODS Following a single oral dose of the sustained-release alfuzosin hydrochloride capsules （ test formulation） and conventional tablets （ reference formulation） to each of the 6 healthy beagle dogs in a randomized crossover design, the plasma levels of the active drugs at different-time points were determined by HPLC and the plasma concentration-time curves of these formulations were obtained, The pharmacokinetic parameters as well as the relative bioavailability were ana- lyzed. RESULTS The tmax values of the test formulation and reference formulation were （ 1. 42 ± 0. 49 ） and （0. 79 ± 0. 19 ） h, The ρmax values were （323.92 ±70.82） and（508.31 ± 120.62） μg·L^-1,and the AUC0-t were （1 082.99 ±290.75） and（1174.56 ± 336, 31 ）μg·h·L^-1 , respectively. The relative bioavailability of the test formulation was found to be（92. 20 ± 14. 94）% compared with the reference formulation . The variance analysis showed no significant difference between the test and reference formulation in periods and formulations（P 〉 0.05） ,but significant difference was obtained in subjects , The 90% confidence interval of AUC0-t of the test formulation was 82. 5% - 108. 2 %, compared with the reference formulation. CONCLUSION Compared with the alfuzosin hydrochloride conventional tablets,the sustained-release alfuzosin hydrochloride capsules have longer action time in dogs and similar relative bioavailability.

关 键 词：盐酸阿呋唑嗪 反相高效液相色谱法 缓释胶囊 药动学 生物等效性 相对生物利用度 

分 类 号：R969[医药卫生—药理学]