[1]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.
 YU Mingjie,SUN Fengjun,XIONG Lirong,et al.Pharmacokinetics and pharmacodynamics of injectable dex-rabrazole for healthy people[J].J Third Mil Med Univ,2021,43(17):1696-1702.
点击复制

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(/HTML )
分享到:

《第三军医大学学报》[ISSN:1000-5404/CN:51-1095/R]

卷:
43卷
期数:
2021年第17期
页码:
1696-1702
栏目:
药学
出版日期:
2021-09-15

文章信息/Info

Title:
Pharmacokinetics and pharmacodynamics of injectable dex-rabrazole for healthy people
作者:
喻明洁孙凤军熊丽蓉程林戴青李小川张枢袁小青陈勇川
陆军军医大学(第三军医大学)第一附属医院药剂科;苏州旭辉检测有限公司
Author(s):
YU Mingjie SUN Fengjun XIONG Lirong CHENG Lin DAI Qin LI Xiaochuan ZHANG Shu YUAN Xiaoqing CHEN Yongchuan
Department of Pharmacy, First Affiliated Hospital, Army Medical University (Third Military Medical University), Chongqing, 400038; 2Suzhou Xuhui Analysis Co., Ltd, Suzhou, Jiangsu Province, 215000, China
 
关键词:
右旋雷贝拉唑高效液相质谱法药代动力学药效学
Keywords:
dex-rabeprazole liquid chromatography with tandem mass spectrometry pharmacokinetics pharmacodynamics
分类号:
R969.1; R969.4; R975.6
文献标志码:
A
摘要:

目的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。结果受试者第1、5天20 mg/q12h右旋组的主要药代动力学参数:Cmax为(1.70±0.46)、(1.74±0.49)μg·mL-1,AUC0-t为(2.19±0.59)、(2.21±0.51) h·μg·mL-1,高于其他3组;Tmax为(0.51±0.03)、(0.50±0.00)h,与其他3组相当;T1/2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:

ObjectiveTo study the pharmacokinetic and pharmacodynamic characteristics of dex-rabeprazole for injection at different doses in healthy subjects and to evaluate its safety. MethodsA 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 value 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. ResultsThe pharmacokinetic parameters on the first and fifth days of the subjects after intravenous infusion of dex-rabeprazole 20 mg/q12h were Cmax 1.70±0.46 and 1.74±0.49 μg·mL-1 and AUC0-t 2.19±0.59 and 2.21±0.51 μg·mL-1 (significantly higher than the other 3 groups); Tmax 0.51±0.03 and 0.50±0.00 h (similar to the other 3 groups); and T1/2 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. ConclusionInjectable dex-rabeprazole shows good pharmacokinetic and pharmacodynamics effects, and has sound safety to healthy subjects.

参考文献/References:

[1]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.
CHEN Q C, ZHAO J, ZHANG J Y. The pharmacological and clinical research progress of rabeprazole[J]. West China J Pharm Sci,2014,29(4):467-468. DOI:10.13375/j.cnki.wcjps.2014.04.038.
[2]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.
[3]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. 
YUAN H Y, WANG Y Q, ZHANG H W, et al. Combined pharmacokinetics-pharmacodynamics study of rabeprazole in inhibition of gastric acid secretion[J]. Her Med, 2014, 33(6): 699-702. DOI:10.3870/yydb.2014.06.002.
[4]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. 
ZHANG C L, LUO H J, JIANG Q, et al. Improved process of dexrabeprazole sodium[J]. J China Pharm Univ, 2018, 49(3): 291-294. DOI:10.11665/j.issn.1000-5048.20180306.
[5]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.
[6]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.
[7]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.
[8]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. 
LI P J, TAN S Z, ZENG J L, et al. Assay of dexrabeprazole sodium for injection by high performance liquid chromatography[J]. Appl Chem Ind, 2016, 45(2): 373-376. DOI:10.16581/j.cnki.issn1671-3206.20151224.040.
[9]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. 
XU Q H, LI Z H, HUANG F F, et al. Comparison of the effects of rabeprazole sodium and its racemes on experimental gastric ulcer in rats[J]. Chin J New Drugs, 2015, 24(8): 917-923. 
[10]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.
[11]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.
SHAO H R, CHEN X F, WANG X B, et al. Pharmacokinetic study of enteric coated (R)-rabeprazole sodium in Beagle dogs[J]. Chin J Pharm Anal, 2018, 38(9): 1523-1529. DOI:10.16155/j.0254-1793.2018.09.09. 
[12]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. 
LI X H, XIE H T, LIANG D H, et al. Determination of dexrabeprazole and levrabeprazole in human plasma by HPLC-MS/MS and its pharmacokinetic study[J]. Chin J New Drugs, 2021, 30(1): 43-49.
[13]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. 

更新日期/Last Update: 2021-09-03