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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AUC_(0→t)、C_(max)、t_(max)分别为(3 887.74±2 766.08)ng·h·ml~(-1)、(1 009.95±321.73)ng·ml~(-1)、(2.42±0.89)h;参比制刺兰索拉唑的AUC_(0→t)、C_(max)、t_(max)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AUC_(0→t)、C_(max)、t_(max)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AUC_(0→t)、C_(max)、t_(max)分别为(291.52±131.81)ng·h·ml~(-1)、(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AUC_(0→t),C_(max)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。
Objective: To evaluate the bioequivalence of lansoprazole and its metabolites. Methods: The plasma concentrations of lansoprazole and its metabolites were determined by LC-MS / MS. Twenty healthy male volunteers were randomized to receive bioequivalence evaluations of crossover single-dose test and reference preparations. Results: The values of AUC_ (0 → t), C_ (max) and t_ (max) of the tested formulations of lansoprazole were (3 887.74 ± 2 766.08) ng · h · ml -1 and 1 009.95 ± 321.73) ng · ml ~ (-1) and (2.42 ± 0.89) h, respectively. The AUC_ (0 → t), C_max and t_max of the reference lansoprazole were (3 895.25 ± 2 809.82 ng · h · ml -1, (150 ± 14 ± 480.22) ng · ml -1, (2.29 ± 1.07) h. The AUC_ (0 → t), C_ (max) and t_ (max) of the tested 5-hydroxy-Lansoprazole were (278.44 ± 106.60) ng · h · ml -1 and (95.65 ± 48.50) ng · ml ~ (-1) and (2.29 ± 0.84) h, respectively. The AUC_ (0 → t), C max and t max of the reference drug 5-hydroxylan Loprazole were (291.52 ± 131.81) ng · h · ml ~ (-1), (113.81 ± 66.36) ng · ml ~ (-1), (2.16 ± 1.11) h. The relative bioavailabilities of lansoprazole and 5-hydroxy-lansoprazole in the test preparations were (106.1% ± 32.7%) and (102.43% ± 38.87%), respectively. The main pharmacokinetic parameters of lansoprazole and 5-hydroxy-lansoprazole were not significantly different by the cross-test analysis of variance. The AUC_ (0 → t) and C_ (max) The double unilateral t-test showed that 90% confidence intervals were all within the valid confidence interval. Conclusion: The two formulations of lansoprazole are bioequivalent with lansoprazole and 5-hydroxy-lansoprazole plasma concentrations.