目的建立测定血浆中尼扎替丁浓度的HPLC,并应用此方法研究国产尼扎替丁片和国产尼扎替丁胶囊的生物等效性。方法采用随机双周期两制剂交叉试验设计,用建立的HPLC对20名健康受试者po 300mg尼扎替丁片(受试制剂)和300mg尼扎替丁胶囊(参比制剂)后12h内多点抽取静脉血进行血药浓度检测。计算主要动力学参数,并评价2种制剂的生物等效性。ρ_max和AUC_0-t,AUC_0-inf采用方差分析和双单侧t检验,t_max进行秩和检验。结果受试制剂和参比制剂中尼扎替丁的达峰时间t_max分别为(2.05±0.32)和(2.00±0.32)h,最大血药浓度ρ_max分别为(2.04±0.63)和(1.97±0.69)mg·L^-1,用梯形法计算,血药浓度-时间曲线下面积AUC_0-12分别为(7.50±1.49)和(7.23±1.52)mg·h·L^-1,AUC_0-inf分别为(8.31±1.70)和(8.01±1.67)mg·h·L^-1。结论以AUC_0-12计算,与参比制剂相比,受试制剂的相对生物利用度为(104.4±11.1)%。受试制剂与参比制剂卫欣比较,经检验AUC_0-12,ρ_max和t_max均符合生物等效性要求,结果表明,2种制剂生物等效。

OBJECTIVE To develop a high-performance liquid chromatography for evaluating the bioequivalence of two nizatidine preparations in the healthy volunteers.METHODS A single oral dose of 300 mg nizatidine tablets and 300 mg nizatidine capsules was given to 20 healthy male volunteer in a randomized cross-over design.Nizatidine concentrations in plasma were determined by HPLC assay.RESULTS The pharmacokinetic parameters of nizatidine tablets and capsules were shown as follow:t_max(2.05±0.32) and(2.00±0.32) h,ρ_max(2.04 ± 0.63) and(1.97 ± 0.69) mg·L^-1,AUC_0-12(7.50±1.49) and(7.23±1.52) mg·h·L^-1,AUC_0-inf(8.31±1.70) and(8.01±1.67) mg·h·L^-1.CONCLUSION The two formulations were bioequivalent according to the statistical analysis.