中国新药杂志

右兰索拉唑缓释胶囊健康人体生物等效性及安全性评价

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杨薇 ¹ , 于爽 ¹ , 许文苑 ² , 高振月 ² , 李浩 ³ , 杨海淼 ¹

中国新药杂志 | 临床研究 2021,30(5): 417-423

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中国新药杂志 |临床研究 2021 , 30 (5) : 417 -423

右兰索拉唑缓释胶囊健康人体生物等效性及安全性评价

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杨薇¹, 于爽¹, 许文苑², 高振月², 李浩³, 杨海淼¹

作者信息

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

通讯作者:

杨海淼，女，主任医师，主要从事药动学和临床试验管理研究。联系电话：（0431）86177635，E-mail：315597629@qq.com。

作者简介:

杨薇，女，博士，主治医师，主要从事药物临床试验及管理工作的研究。联系电话：（0431）86177876，E-mail：ywonline@163.com。

Bioequivalence and safety evaluation of dexlansoprazole modification release capsule in human

Wei YANG¹, Shuang YU¹, Wen-yuan XU², Zhen-yue GAO², Hao LI³, Hai-miao YANG¹

Affiliations

¹Phase Ⅰ Clinical Trial Research Ward, Affiliated Hospital to Changchun University of Traditional Chinese Medicine, Changchun 130021, China

²Chia Tai Tianqing Pharmaceutical Co., Ltd., Nanjing 210000, China

³Shanghai Xihua Testing Technology Service Co., Ltd., Shanghai 201200, China

出版时间: 2021-03-15

文章导航

摘要

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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 WinNonlin（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。

关键词

右兰索拉唑缓释胶囊 / 生物等效 / 安全性 / 临床评价

Abstract

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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 single-dose 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 and safe.

Key words

dexlansoprazole modification release capsule / bioequivalence / safety / clinical evaluation

引用本文

杨薇, 于爽, 许文苑, 高振月, 李浩, 杨海淼. 右兰索拉唑缓释胶囊健康人体生物等效性及安全性评价. 中国新药杂志, 2021 , 30 (5) : 417 -423 .

Wei YANG, Shuang YU, Wen-yuan XU, Zhen-yue GAO, Hao LI, Hai-miao YANG. Bioequivalence and safety evaluation of dexlansoprazole modification release capsule in human[J]. Chinese Journal of New Drugs, 2021 , 30 (5) : 417 -423 .

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2021年第30卷第5期

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首发时间：2026-10-29
出版时间：2021-03-15

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录用日期：2020-05-30

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作者信息

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

通讯作者:

杨海淼，女，主任医师，主要从事药动学和临床试验管理研究。联系电话：（0431）86177635，E-mail：315597629@qq.com。

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https://castjournals.cast.org.cn/joweb/zgxyzz/CN/1322627818425532823

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2种不同金属材料的力学参数

科 Family	属数 Number of genus	种数 Number of species	占总种数比例 Percentage of total species (%)	属 Genus	种数 Number of species	占总种数比例 Percentage of total species (%)
鹅膏菌科Amanitaceae	2	11	5.26	鹅膏菌属 Amanita	10	4.78
小菇科 Mycenaceae	2	12	5.74	丝盖伞属 Inocybe	5	2.39
多孔菌科 Polyporaceae	8	14	6.70	蜡蘑属 Laccaria	5	2.39
红菇科 Russulaceae	3	23	11.00	小皮伞属 Marasmius	6	2.87
				小菇属 Mycena	11	5.26
				光柄菇属 Pluteus	5	2.39
				红菇属 Russula	17	8.13
				栓菌属 Trametes	5	2.39

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