摘要
目的:建立人血浆中比索洛尔浓度的HPLC-MS测定方法,并评价国产与进口富马酸比索洛尔片的人体生物等效性。方法:18例男性健康受试者随机分成两组,分别交叉口服受试制剂和参比制剂各5mg,采用HPLC- MS法测定人血浆中比索洛尔的浓度。结果:血浆中比索洛尔的最低定量限为0.05 ng·mL^(-1),在0.05~120 ng·mL^(-1)范围内线性关系良好,批内及批间精密度RSD均小于8%。受试制剂与参比制剂的各主要药动学参数:T_(max)分别为(1.9±0.9)和(1.9±0.7)h,C_(max)分别为(20.3±3.3)和(20.6±3.3)ng·mL^(-1),t_(1/2)分别为(8.4±1.2)和(8.1±1.0)h,用梯形法计算AUC_(0~48h)分别为(244.0±38.5)和(249.5±41.0)ng·h·mL^(-1)。两种制剂的主要药动学参数C_(max)和AUC_(0~48h)经对数转换后进行方差分析及双单侧t检验,并计算90%置信区间,表明两种制剂生物等效,相对生物利用度为(98.4±10.6)%。结论:两种制剂生物等效。
Objective: To establish a HPLC-MS method for the determination of bisoprolol in human plasma and to evaluate the bioequivalence of domestic and imported bisoprolol fumarate tablets in healthy volunteers. Methods : A 5 mg dose of the reference or test drug was given to 18 healthy male volunteers in a randomized two-way crossover design and the plasma concentration of the drug was assayed by HPLC-MS. The main pharmacokinetic parameters and bioequivalence of the two formulations were evaluated. Results: The low determination limit of bisoprolol in plasma was 0.05 ng· mL^-1 and a good linearity was obtained over the range of 0.05 - 120 ng· mL^-1. The intra-and inter-run standard deviation was less than 8%. The pharmacokinetic parameters of the test and reference drugs were as follows: T (1.9±0.9) and (1.9±0.7) h, Cmax(20.3±3.3) and (20.6±3.3) ng·mL^-1, t1/2(8.4±1.2) and (8.1 ± 1.0) h, and AUC0-48h(244.0±38.5) and (249.5±41.0) ng·h·mL^-1, respectively. The relative bioavailability of the test product to the reference was (98.4 ± 10.6) %. Conclusion: The two formulations were bioequivalent.
出处
《中国新药杂志》
CAS
CSCD
北大核心
2007年第20期1712-1715,共4页
Chinese Journal of New Drugs