右兰索拉唑缓释胶囊健康人体生物等效性及安全性评价  

Bioequivalence and safety evaluation of dexlansoprazole modification release capsule in human

作　　者：杨薇[1] 于爽 许文苑 高振月 李浩 杨海淼[1] YANG Wei;YU Shuang;XU Wen-yuan;GAZhen-yue;LI Hao;YANG Hai-miao(PhaseⅠClinical Trial Research Ward,Affiliated Hospital to Changchun University of Traditional Chinese Medicine,Changchun 130021,China;Chia Tai Tianqing Pharmaceutical Co.,Ltd.,Nanjing 210000,China;Shanghai Xihua Testing Technology Serice Co.,Lud.,Shanghai 201200,China)

机构地区：[1]长春中医药大学附属医院Ⅰ期临床试验研究室,长春130012 [2]正大天晴药业集团股份有限公司,南京210000 [3]上海熙华检测技术服务有限公司,上海201200

出　　处：《中国新药杂志》2021年第5期417-423,共7页Chinese Journal of New Drugs

摘　　要：目的:评价右兰索拉唑缓释胶囊在健康受试者空腹、餐后状态下的人体生物等效性及安全性。方法:采取随机、开放、四周期、两交叉单次给药设计,空腹组及餐后组各有30例健康受试者入选,采用高效液相色谱-串联质谱法测定受试者每周期口服右兰索拉唑缓释胶囊受试制剂或参比制剂(Dexilant^(■))后15个不同时间点的右兰索拉唑浓度。采用平均生物等效性(average bioequivalence,ABE)方法评价生物等效性,应用Phoenix Win Nonlin(Pharsight Corporation,Version 6.4),采用混合效应模型,以置信区间法评价生物等效性。试验全程对受试者不良事件进行监测。结果:空腹试验与餐后试验各有30例受试者完成试验,空腹试验受试者平均年龄(38.90±10.31)岁,男女比例为1∶1.31,C_(max),AUC_(0-t)和AUC_(0-∞)几何均值比值分别为102.44%,103.20%和103.09%,90%置信区间分别为93.92~111.74%,98.57%~108.03%和98.32%~108.09%;餐后试验受试者平均年龄(41.30±11.12)岁,男女比例为1∶1.50,C_(max),AUC_(0-t)和AUC_(0-∞)几何均值比值分别为101.04%,101.83%和101.49%;90%置信区间分别为95.76%~106.60%,98.43%~105.35%和97.90%~105.22%。试验中最常见(≥2%)的不良事件为腹泻、腹痛、恶心,与试验相关且非预期不良事件主要为心电图T波低平(4,6.67%)、尿酮体升高(1,1.67%)、心动过速(1,1.67%)。所有不良事件均未采用治疗措施并恢复正常,无严重不良事件。结论:2种右兰索拉唑缓释胶囊制剂生物等效,健康人体中安全性良好。Objective: To evaluate the bioequivalence and safety of dexlansoprazole sustained-release capsule in healthy subjects on fasting and postprandial state. Methods: A random,open,four-cycle,two-cross and singledose design was adopted. Healthy subjects were grouped to either fasting or postprandial group( n = 30 in each group). The concentrations of lansoprazole at 15 different time points after oral test or reference preparation( Dexilant^(■))were determined by high-performance liquid chromatography-tandem mass spectrometry. Average bioequivalence( ABE) method was adopted. The bioequivalence was evaluated using mixed effect model by Phoenix WinNonlin( Pharsight Corporation,Version 6. 4) and confidence interval method. Adverse events( AE) were monitored during the whole test. Results: Thirty subjects completed the test in each of fasting or postprandial group. The average age of the subjects was 38. 90 ± 10. 31 in fasting group,the ratio of male to female was 1 ∶ 1. 31. The geometric average ratios of tested C_(max),AUC_(0-t)and AUC_(0-∞)were 102. 44%,103. 20% and 103. 09%,and the 90% confidence intervals were 93. 92% ~ 111. 74%,98. 57% ~ 108. 03% and 98. 32% ~ 108. 09%,respectively.The average age of the subjects was( 41. 30 ± 11. 12) years in postprandial group,and the ratio of male to female was 1∶ 1. 50,with the standard deviation Swr of each individual less than 0. 294. The geometric average ratios of C_(max),AUC_(0-t)and AUC_(0-∞)were 101. 04%,101. 83% and 101. 49%,with the 90% confidence intervals 95. 76% ~106. 60%,98. 43% ~ 105. 35% and 97. 90% ~ 105. 22%,respectively. The most common AE( ≥2%) occurred during the experiment mainly included diarrhea,abdominal pain,and nausea. The unanticipated AE correlated with the test were T wave lowland( 4,6. 67%),urine ketone body raised( 1,1. 67%) and tachycardia( 1,1. 67%).All AEs were not treated and recovered to normal. No serious adverse events( SAE) occurred. Conclusion: Two formulations of dexlansoprazole sustained release capsules are bioequivalent a

关 键 词：右兰索拉唑缓释胶囊 生物等效 安全性 临床评价 

分 类 号：R969.4[医药卫生—药理学]