三种尼扎替丁制剂在中国健康人体的药动学及生物等效性

Pharmacokinetics and bioequivalence of three nizatidine preparations in healthy chinese volunteers

目的:评价健康受试者单剂量口服受试尼扎替丁片剂、胶囊以及参比尼扎替丁片剂的人体药动学与生物等效性。方法:采用3种制剂3周期随机交叉试验设计,HPLC法测定18例男性健康受试者单剂量口服150mg受试尼扎替丁片剂、胶囊和参比尼扎替丁片后的血药浓度;采用非室模型计算药动学参数;AUC,Cmax经对数转换后进行方差分析并计算90%置信区间。结果:受试尼扎替丁片剂、胶囊和参比尼扎替丁片剂的Cmax分别为(1280±359),(1377±438)和(1140±269)ng·mL-1;tmax分别为(0.986±0.358),(1.069±0.362)和(1.125±0.464)h;t1/2分别为(1.556±0.312),(1.441±0.309)和(1.511±0.259)h;AUC0-t分别为(3864.50±662.77),(3775.06±596.18)和(3685.83±561.46)ng·h·mL-1;AUC0-∞分别为(3896.55±668.89),(3798.17±605.86)和(3711.37±563.63)ng·h·mL-1。结论:受试制剂尼扎替丁片、胶囊与参比尼扎替丁片具有生物等效性。

Objective： To evaluate the pharmacokinetics and bioequivalence of nizatidine tablets and capsules （test samples） with nizatidine tablets （reference samples） in the healthy volunteers. Methods： This was an open randomized, three periods cross over study that recruited eighteen healthy male volunteers. Each volunteer was randomly administered with a single oral dose of nizatidine （test or reference samples） 150 mg. The plasma concentrations of nizatidine were determined by HPLC. Non-compartment models was used in analysis of pharmacokinetic parameters. Logarithm-transformed Cmax and AUC were analyzed by the analysis of variance（ANOVA） and 90% confidence intervals. Results： The Cmax of test nizatidine tablets, capsules and reference tablets were（ 1 280 ± 359）, （ 1 377 ± 438） and （1 140 ± 269） ng·mL^-1, respectively, tmax= were （0.986 ± 0.358）, （1.069 ± 0.362） and （1.125 ± 0.464） h; respectively. t1/2 were （1.556 ± 0.312）, （1.441 ± 0.309） and （1.511 ± 0.259） h, respectively; AUC0-t were （3 864.50 ± 662.77）, （3 775.06 ± 596.18） and （3 685.83 ± 561.46） ng·h·mL^-1, respectively. AUC0-∞, were （3 896.55 ± 668.89）, （3 798.17 ± 605.86） and （3 711.37 ± 563.63） ng·h·mL^-1, respectively. Conclusion： The test nizatidine tablets and capsules are bioequivalent with the reference tablets.