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注射用右旋雷贝拉唑钠在健康人体内的药代动力学和药效学研究
Pharmacokinetics and pharmacodynamics of injectable dex-rabrazole for healthy people
- 第三军医大学学报 2021年43卷第17期 页码：1696-1702
- 作者机构：
- 作者简介：
- 基金信息：重庆市社会事业与民生保障科技创新专项项目(CSTC2017shmsA130043)
DOI：10.16016/j.1000-5404.202103050
中图分类号：收稿：2021-03-05，
纸质出版：2021-09-15
- 稿件说明：
移动端阅览
喻明洁, 孙凤军, 熊丽蓉, 等. 注射用右旋雷贝拉唑钠在健康人体内的药代动力学和药效学研究[J]. 第三军医大学学报, 2021,43(17):1696-1702.
Mingjie YU, Fengjun SUN, Lirong XIONG, et al. Pharmacokinetics and pharmacodynamics of injectable dex-rabrazole for healthy people[J]. Journal of Third Military Medical University, 2021, 43(17): 1696-1702.
喻明洁, 孙凤军, 熊丽蓉, 等. 注射用右旋雷贝拉唑钠在健康人体内的药代动力学和药效学研究[J]. 第三军医大学学报, 2021,43(17):1696-1702. DOI： 10.16016/j.1000-5404.202103050.
Mingjie YU, Fengjun SUN, Lirong XIONG, et al. Pharmacokinetics and pharmacodynamics of injectable dex-rabrazole for healthy people[J]. Journal of Third Military Medical University, 2021, 43(17): 1696-1702. DOI： 10.16016/j.1000-5404.202103050.
摘要
目的
2
探讨不同剂量注射用右旋雷贝拉唑钠在健康受试者体内的药代动力学和药效学特征
并评价其安全性。
方法
2
采用随机、开放、阳性药对照试验设计
筛选40例健康受试者分为4组（
n
=10）
分别静脉滴注注射用右旋雷贝拉唑钠10 mg/qd（10 mg/qd右旋组）、10 mg/q12h（10 mg/q12h右旋组）、20 mg/q12h（20 mg/q12h右旋组）和注射用雷贝拉唑钠20 mg/q12h（20 mg/q12h消旋组）
于第1、5天给药后监测胃内24 h pH值
并用液-质联用(LC-MS/MS)法测定血液中右旋雷贝拉唑浓度
数据用WinNonlin7.0和SAS9.4软件分析处理。
结果
2
受试者第1、5天20 mg/q12h右旋组的主要药代动力学参数：C
max
为(1.70±0.46)、(1.74±0.49)μg·mL
-1
AUC
0-t
为(2.19±0.59)、(2.21±0.51) h·μg·mL
-1
高于其他3组；T
max
为(0.51±0.03)、(0.50±0.00)h
与其他3组相当；T
1/2
为(1.93±0.73)、(1.82±0.67)h
高于10 mg/qd右旋组和10 mg/q12h右旋组
稍低于20 mg/q12h消旋组。用药第1、5天后20 mg/q12h右旋组胃内pH
>
4.0的时间百分比为(82.27±10.13)%、(93.16±5.84)%
高于其他3组；20 mg/q12h消旋组胃内pH
>
4.0的时间百分比高于10 mg/qd右旋组和10 mg/q12h右旋组。20 mg/q12h右旋组出现1例1件轻度不良事件（大腿后侧酸痛）
自行好转
各组均未出现严重不良事件。
结论
2
注射用右旋雷贝拉唑钠20 mg/q12h的药代动力学和药效学效果较好
且健康受试者服药后安全性良好。
Abstract
Objective
2
To study the pharmacokinetic and pharmacodynamic characteristics of dex-rabeprazole for injection at different doses in healthy subjects and to evaluate its safety.
Methods
2
A randomized
open
positive drug control trial design was adopted in this study. Forty healthy subjects were divided into 4 groups (
n
=10)
and underwent intravenous infusion of dex-rabeprazole at 10 mg/qd
10 mg/q12h
20 mg/q12h and rabeprazole sodium 20 mg/q12h
respectively. The intragastric pH va
lue was monitored for 24 h on the first and fifth days after administration. Liquid chromatography with tandem mass spectrometry (LC-MS/MS) was used to determine the blood dex-rabeprazole concentration. WinNonlin7.0 and SAS9.4 software was conducted to analyze and process the obtained data.
Results
2
The pharmacokinetic parameters on the first and fifth days of the subjects after intravenous infusion of dex-rabeprazole 20 mg/q12h were C
max
1.70±0.46 and 1.74±0.49 μg·mL
-1
and AUC
0-t
2.19±0.59 and 2.21±0.51 μg·mL
-1
(significantly higher than the other 3 groups); T
max
0.51±0.03 and 0.50±0.00 h (similar to the other 3 groups); and T
1/2
1.93±0.73 and 1.82±0.67 (higher than the 10 mg/qd and 10 mg/q12h groups and slightly lower than the rabeprazole sodium 20 mg/q12h). The percentage of time with intragastric pH value
>
4.0 after the first and fifth days of medication was (82.27±10.13)% and (93.16±5.84)% in the dex-rabeprazole 20 mg/q12h group
statistically higher than those in the other 3 groups. The percentage was also higher in the rabeprazole sodium 20 mg/q12h group than the 10 mg/qd and 10 mg/q12h groups. One case from the dex-rabeprazole 20 mg/q12h group experienced mild adverse event (pain in the back of the thigh) and relieved after that spontaneously. No serious adverse events were observed in each group.
Conclusion
2
Injectable dex-rabeprazole shows good pharmacokinetic and pharmacodynamics effects
and has sound safety to healthy subjects.
关键词
Keywords
references
陈 庆财 赵 俊 张 建义 雷贝拉唑的药理与临床研究进展 华西药学杂志 2014 29 4 467 468 10.13375/j.cnki.wcjps.2014.04.038 陈庆财, 赵俊, 张建义. 雷贝拉唑的药理与临床研究进展[J]. 华西药学杂志, 2014, 29(4): 467-468. DOI: 10.13375/j.cnki.wcjps.2014.04.038.
BAKHEIT A H AL-KAHTANI H M ALBRAIKI S Rabeprazole: a comprehensive profile Profiles Drug Subst Excip Relat Methodol 2021 46 137 183 10.1016/bs.podrm.2020.07.003 BAKHEIT A H, AL-KAHTANI H M, ALBRAIKI S. Rabeprazole: a comprehensive profile[J]. Profiles Drug Subst Excip Relat Methodol, 2021, 46: 137-183. DOI: 10.1016/bs.podrm.2020.07.003.
袁 红宇 王 永庆 张 宏文 雷贝拉唑抑制胃酸分泌的药动学-药效学结合研究 医药导报 2014 33 6 699 702 10.3870/yydb.2014.06.002 袁红宇, 王永庆, 张宏文, 等. 雷贝拉唑抑制胃酸分泌的药动学-药效学结合研究[J]. 医药导报, 2014, 33(6): 699-702. DOI: 10.3870/yydb.2014.06.002.
张 春来 罗 宏军 姜 琦 右旋雷贝拉唑钠的制备工艺改进 中国药科大学学报 2018 49 3 291 294 10.11665/j.issn.1000-5048.20180306 张春来, 罗宏军, 姜琦, 等. 右旋雷贝拉唑钠的制备工艺改进[J]. 中国药科大学学报, 2018, 49(3): 291-294. DOI: 10.11665/j.issn.1000-5048.20180306.
MIURA M KAGAYA H TADA H Enantioselective disposition of rabeprazole in relation to CYP2C19 genotypes Br J Clin Pharmacol 2006 61 3 315 320 10.1111/j.1365-2125.2005.02566.x MIURA M, KAGAYA H, TADA H, et al . Enantioselective disposition of rabeprazole in relation to CYP2C19 genotypes[J ] . Br J Clin Pharmacol, 2006, 61(3): 315-320. DOI: 10.1111/j.1365-2125.2005.02566.x.
PAI V PAI N Randomized, double-blind, comparative study of dexrabeprazole 10 mg versus rabeprazole 20 mg in the treatment of gastroesophageal reflux disease World J Gastroenterol 2007 13 30 4100 4102 10.3748/wjg.v13.i30.4100 PAI V, PAI N. Randomized, double-blind, comparative study of dexrabeprazole 10 mg versus rabeprazole 20 mg in the treatment of gastroesophageal reflux disease[J]. World J Gastroenterol, 2007, 13(30): 4100-4102. DOI: 10.3748/wjg.v13.i30.4100.
JAIN S C RELIEF STUDY GROUP A postmarketing surveillance study of dexrabeprazole in the treatment of acid peptic disorders J Indian Med Assoc 2009 107 2 111 113 http://www.ncbi.nlm.nih.gov/pubmed/19585824 JAIN S C, RELIEF STUDY GROUP. A postmarketing surveillance study of dexrabeprazole in the treatment of acid peptic disorders[J]. J Indian Med Assoc, 2009, 107(2): 111-113.
李 蒲江 谭 淑珍 曾 巨澜 高效液相色谱法测定注射用右旋雷贝拉唑钠粉针剂含量 应用化工 2016 45 2 373 376 10.16581/j.cnki.issn1671-3206.20151224.040 李蒲江, 谭淑珍, 曾巨澜, 等. 高效液相色谱法测定注射用右旋雷贝拉唑钠粉针剂含量[J]. 应用化工, 2016, 45(2): 373-376. DOI: 10.16581/j.cnki.issn1671-3206.20151224.040.
许 庆华 李 宗河 黄 菲菲 雷贝拉唑钠拆分体对大鼠实验性胃溃疡作用的比较研究 中国新药杂志 2015 24 8 917 923 https://www.cnki.com.cn/Article/CJFDTOTAL-ZXYZ201508016.htm 许庆华, 李宗河, 黄菲菲, 等. 雷贝拉唑钠拆分体对大鼠实验性胃溃疡作用的比较研究[J]. 中国新药杂志, 2015, 24(8): 917-923.
GAO Y H XU J X SU Z X The chiral bioconversion and preclinical pharmacokinetic analysis of (R)-(+)-rabeprazole in beagle dogs by HPLC and HPLC-MS/MS Biomed Chromatogr 2013 27 11 1380 1386 10.1002/bmc.2932 GAO Y H, XU J X, SU Z X, et al . The chiral bioconversion and preclinical pharmacokinetic analysis of (R)-(+)-rabeprazole in beagle dogs by HPLC and HPLC-MS/MS[J ] . Biomed Chromatogr, 2013, 27(11): 1380-1386. DOI: 10.1002/bmc.2932.
邵 华荣 陈 相峰 王 晓波 右旋雷贝拉唑钠肠溶片在Beagle犬体内的药代动力学 药物分析杂志 2018 38 9 1523 1529 10.16155/j.0254-1793.2018.09.09 邵华荣, 陈相峰, 王晓波, 等. 右旋雷贝拉唑钠肠溶片在Beagle犬体内的药代动力学[J]. 药物分析杂志, 2018, 38(9): 1523-1529. DOI: 10.16155/j.0254-1793.2018.09.09.
李 相鸿 谢 海棠 梁 大虎 HPLC-MS/MS法测定人血浆中右旋雷贝拉唑和左旋雷贝拉唑浓度及其人体药动学研究 中国新药杂志 2021 30 1 43 49 https://www.cnki.com.cn/Article/CJFDTOTAL-ZXYZ202101008.htm 李相鸿, 谢海棠, 梁大虎, 等. HPLC-MS/MS法测定人血浆中右旋雷贝拉唑和左旋雷贝拉唑浓度及其人体药动学研究[J]. 中国新药杂志, 2021, 30(1): 43-49.
MIURA M TADA H SATOH S Determination of rabeprazole enantiomers and their metabolites by high-performance liquid chromatography with solid-phase extraction J Pharm Biomed Anal 2006 41 2 565 570 10.1016/j.jpba.2005.12.016 MIURA M, TADA H, SATOH S, et al . Determination of rabeprazole enantiomers and their metabolites by high-performance liquid chromatography with solid-phase extraction[J ] . J Pharm Biomed Anal, 2006, 41(2): 565-570. DOI:10.1016/j.jpba.2005.12.016.
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