兰索拉唑及其代谢产物的生物等效性研究

目的:评价兰索拉唑及其代谢产物的生物等效性.方法:用LC-MS/MS测定兰索拉唑及其代谢产物的血药浓度.20名健康男性志愿者随机分组、自身交叉口服单剂量受试制剂和参比制剂进行生物等效性评价.结果:受试制剂兰索拉唑的AUC0→t、Cmax、tmax分别为(3887.74±2 766.08 )ng·h·ml -、(1 009.95±321.73 )ng·ml-1、(2.42±0.89)h;参比制剂兰索拉唑的AUC0→t、Cmax、tmax分别为(3 895.25±2 809.82 )ng·h·ml-1、(1 150.74±480.22) ng·ml-1、(2.29±1.07)h.受试制剂5-羟基兰索拉唑的AUC0+t、Cmax、tmax分别为(278.44±106.60) ng·h·ml-1、(95.65±48.50 )ng · ml -1、(2.29±0.84)h;参比制剂5-羟基兰索拉唑的AUC0+t、Cmax、tmax分别为(291.52±131.81) ng·h·ml -、(113.81±66.36) ng ·ml-1、(2.16±1.11)h.受试制剂相比参比制剂的兰索拉唑、5-羟基兰索拉唑的人体相对生物利用度分别是(106.1％±32.7％)、(102.43％±38.87％).受试制剂相对参比制剂的兰索拉唑、5-羟基兰索拉唑主要药动学参数经交叉试验方差分析差异无统计学意义,两制剂的AUC0+t,Cmax经双单侧t检验示90％置信区间均位于有效置信区间范围内.结论:兰索拉唑的2种制剂以兰索拉唑及5-羟基兰索拉唑血药浓度数据评价,具有生物等效性.

Study on the Bioequivalence of Lansoprazole and Its Metabolites

Objective：To evaluate the bioequivalence of lansoprazole and its metabolites.Method：The concentrations of lansoprazole and its metabolites in plasma were determined by LC-MS/MS.Twenty healthy human volunteers were divided randomly into 2 groups,and a crossover and single oral dose of lansoprazole with the dosage of 30 mg of test and reference capsules were administrated, respectively.Result：AUC_（0→t）,C_（max） and t_（max） of test and reference lansoprazole capsules were（3 887.74±2 766.08）ng·h·ml~（-1）, （1 009.95±321.73）ng·ml~（-1） and（2.42±0.89）h,and（3 895.25±2 809·82）ng·h·ml~（-1）,（1 150.74±480.22） ng·ml~（-1） and （2.29±1.07） h,respectively.Those for 5 -hydroxylansoprazole of test and reference capsules were（278.44±106.60） ng·h·ml~（-1）, （95.65±48.50）ng·ml~（-1） and（2.29±0.84）h,and（291.52±131.81） ng·h·ml~（-1）,（113.81±66.36） ng·ml~（-1） and（2.16±1.11 ）h,respectively.Compared with the reference capsules,the bioavailability of lansoprazole and 5-hydroxylansoprazole of test capsules were（106.1%±32.7%） and（102.43%±38.87%）（n = 19）,respectively.Main pharmacokinetic parameters of lansoprazole and 5-hydrpxylansoprazole between test and reference capsules showed no statistical difference.Conclusion;The test and reference capsules are bioequivalent based on the statistical analysis of lansoprazole and 5-hydroxylansoprazole.