奥拉西坦口服溶液的人体生物等效性评价Bioequivalence of oxiracetam oral solutions
刘杰,张国顺,赵云丽,于治国,李久旭
LIU Jie1,ZHANG Guo-shun1,ZHAO Yun-li1,YU Zhi-guo1,LI Jiu-xu2(1.School of Pharmacy
摘要(Abstract)：
目的建立测定人血浆样品中奥拉西坦浓度的HPLC-UV方法,并用于评价奥拉西坦口服溶液的人体生物等效性。方法采用Agilent Zorbax SB-Aq色谱柱(150 mm×4.6 mm,5μm),流动相为0.05 mol.L-1磷酸二氢钾溶液-0.01 mol.L-1高氯酸溶液(体积比为10∶90),流速为0.5 mL.min-1,柱温为20℃;检测波长为215 nm,内标物为鸟嘌呤,测定给药后健康志愿者血浆中奥拉西坦质量浓度,计算相关药动学参数及相对生物利用度。结果 20名志愿者单剂量口服受试制剂与参比制剂后,tmax分别为(0.99±0.48)和(1.28±0.49)h,ρmax分别为(28.79±6.00)和(30.55±7.65)mg.L-1,t1/2分别为(2.93±0.78)和(2.62±1.02)h,AUC0-t分别为(105.09±29.07)和(120.55±39.08)mg.h.L-1,AUC0-∞分别为(113.27±28.91)和(126.89±40.33)mg.h.L-1。以AUC0-t计算,受试制剂的相对生物利用度平均为(92.6±30.0)%。结论受试制剂与参比制剂具有生物等效性。
Objective To develop a simple,selective HPLC-UV method for the determination of oxiracetam concentration in human plasma and evaluate the bioequivalence of oxiracetam oral solutions with the method.Methods A single oral dose of two oxiracetam preparations were given respectively to 20 volunteers in an open randomized two-way cross-over test and the plasma samples collected at predetermined time points were determined by HPLC-UV method.The related parameters of pharmacokinetics were calculated by DAS2.0 program.Results The main pharmacokinetic parameters of oxiracetam in test and reference preparations were as follows:tmax were(0.99±0.48) and(1.28±0.49)h,ρmax were(28.79±6.00) and(30.55±7.65)mg · L-1,t1/2 were(2.93±0.78) and(2.62±1.02)h,AUC0-t were(105.09±29.07) and(120.55±39.08)mg · h · L-1,AUC0-∞ were(113.27±28.91) and(126.89±40.33)mg · h · L-1,respectively.The relative bioavailability of oxiracetam was(92.6±30.0)%.Conclusions The statistical analysis results show that the two preparations are bioequivalent.
关键词(KeyWords)：
奥拉西坦;生物等效性;高效液相色谱法
oxiracetam;bioequivalence;HPLC
基金项目(Foundation):
作者(Author):
刘杰,张国顺,赵云丽,于治国,李久旭
LIU Jie1,ZHANG Guo-shun1,ZHAO Yun-li1,YU Zhi-guo1,LI Jiu-xu2(1.School of Pharmacy
DOI: 10.14066/j.cnki.cn21-1349/r.2012.04.012
参考文献(References)：
- [1]刘治军,胡欣.促智药奥拉西坦的临床和基础研究[J].中华神经外科疾病研究杂志,2005,4(3):286-288.
- [2]纪立伟,胡欣.促智药奥拉西坦研究进展[J].中国药物与临床,2003,3(4):354-356.
- [3]钟大放.以加权最小二乘法建立分析标准曲线的若干问题[J].药物分析杂志,1996,16(5):343-346.
- [4]国家药典委员会.中华人民共和国药典:二部[M].北京:中国医药科技出版社,2010:附录195-199.
- [5]WEI Chun-min,WANG Ben-jie,GUO Rui-chen.Phar-macokinetics of oxiracetam in healthy volunteers[J].Journal of Chinese Pharmaceutical Sciences,2005,14(1):29-32.
- [6]周玉娟,於东晖,焦效兰,等.国产奥拉西坦胶囊剂的相对生物利用度[J].中国新药杂志,1997,6(4):303-305.
- [7]刘治军,李可欣,阴继爱,等.奥拉西坦注射液在中国健康受试者体内的药动学[J].中国医院药学杂志,2005,25(5):404-406.
- [8]高连用,顾以保,李全胜,等.两种奥拉西坦胶囊的人体生物等效性研究[J].中国药学杂志,1999,34(7):474-477.