[1]李晓宇,尚圣兰,熊丽蓉,等.不同剂量注射用泮托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,2018,40(17):1613-1618.
 LI Xiaoyu,SHANG Shenglan,XIONG Lirong,et al.Pharmacokinetics and pharmacodynamics of pantoprazole sodium at different doses in healthy volunteers[J].J Third Mil Med Univ,2018,40(17):1613-1618.
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不同剂量注射用泮托拉唑钠在健康人体内的药代动力学和药效学研究(/HTML )
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《第三军医大学学报》[ISSN:1000-5404/CN:51-1095/R]

卷:
40卷
期数:
2018年第17期
页码:
1613-1618
栏目:
药学
出版日期:
2018-09-15

文章信息/Info

Title:
Pharmacokinetics and pharmacodynamics of pantoprazole sodium at different doses in healthy volunteers
作者:
李晓宇尚圣兰熊丽蓉孙凤军向荣凤邱学文喻明洁王若茜陈勇川
陆军军医大学(第三军医大学)第一附属医院药剂科;解放军第285医院药剂科
Author(s):
LI Xiaoyu SHANG Shenglan XIONG Lirong SUN Fengjun XIANG Rongfeng QIU Xuewen1 YU Mingjie WANG Ruoxi CHEN Yongchuan

Department of Pharmacy, First Affiliated Hospital, Army Medical University (Third Military Medical University), Chongqing, 400038; Department of Pharmacy, No. 285 Hospital of PLA, Handan, Hebei Province, 056001, China

关键词:
泮托拉唑高效液相质谱联用药代动力学药效学
Keywords:
antoprazole liquid chromatography-mass spectrometry/mass spectrometry pharmacokinetics pharmacodynamics
分类号:
R451; R969; R975.6
文献标志码:
A
摘要:

目的    观察不同剂量注射用泮托拉唑钠在中国健康志愿者体内的药代动力学和药效学特征,并评价其安全性。方法    用单中心、随机、开放、平行对照的试验设计,筛选20名健康受试者,采用男女分层区组随机化方法分组,分别静脉滴注40、80 mg注射用泮托拉唑钠(每日2次,连续5 d),给药后监测24 h胃内pH值。用LCMS/MS法测定左旋泮托拉唑钠血药浓度,数据分别用WinNonlin 6.4软件和SAS软件分析处理。结果    首次静脉滴注注射用泮托拉唑钠后,40、80 mg剂量组后左旋泮托拉唑的主要药动学参数:Cmax分别为(2.37±0.61)、(4.56±0.89)μg/mL;AUC(0t)分别为(4.96±3.26)、(10.16±3.16)μg·h/mL;AUC(0∞)分别为(5.17±3.68)、(10.34±3.35)μg·h/mL;t1/2分别为(1.67±0.76)、(1.75±0.57)h;Tmax分别为(0.50±0.01)、(0.53±0.08)h;连续给药5 d后40、80 mg剂量组左旋泮托拉唑的主要药动学参数:Cmax分别为(2.30±0.62)、(4.50±0.71)μg/mL;AUC(0t)分别为(5.02±3.85)、(10.75±3.82)μg·h/mL;AUC(0∞)分别为(5.26±4.35)、(10.98±4.10)μg/mL·h;Cmin,ss分别为(0.03±0.08)、(0.05±0.07)μg/mL;t1/2分别为(1.72±0.78)、(1.80±0.64)h;Tmax分别为(0.52±0.04)、(0.50±0.00)h。用药第1天后40、80 mg剂量组胃内pH>4的时间比例分别为(38.6±20.9)%、(46.9±16.5)%;pH>6的时间比例分别为(25.5±20.6)%、(32.7±7.9)%;用药第5天后胃内pH>4的时间比例分别为(69.6±15.4)%、(80.2±16.6)%;pH>6的时间比例分别为(48.3±13.7)%、(49.7±15.7)%。结    论注射用泮托拉唑钠在健康人体内符合线性药代动力学特征。通过两剂量组药效学参数比较,80 mg剂量组的抑酸效果明显优于40 mg剂量组,且服药后较安全。建议临床使用80 mg每12小时1次。

Abstract:

Objective     To investigate the pharmacokinetic and pharmacodynamic properties of pantoprazole sodium at different doses of injection and explore its safety in healthy Chinese volunteers. MethodsA single center, randomized, open, and parallel controlled trial was designed for this study. Twenty healthy subjects were screened by a stratified randomization method for men and women to receive multiple doses of pantoprazole sodium of 40 and 80 mg (twice daily for 5 consecutive days), respectively. The intragastric pH value was monitored 24 h after administration.S(-)pantoprazole sodium concentration was determined by liquid chromatographymass spectrometry/mass spectrometry (LCMS/MS). The data were analyzed by WinNonlin 6.4 software and SAS software respectively. ResultsAfter the first intravenous infusion of pantoprazole sodium, the main pharmacokinetic parameters of S(-)pantoprazole after 40 and 80 mg groups were as follows: Cmax were 2.37±0.61 and 4.56±0.89 μg/mL; AUC(0-t) 4.96±3.26 and 10.16±3.16 μg·h/mL; AUC(0-∞) 5.17±3.68 and 10.34±3.35 μg·h/mL; t1/2 1.67±0.76 and 1.75±0.57 h; and Tmax 0.50±0.01 and 0.53±0.08 h. After 5 days’ continuous administration, the main pharmacokinetic parameters were as follows: Cmax were 2.30±0.62 and 4.50±0.71 μg/mL; AUC(0-t) 5.02±3.85 and 10.75±3.82 μg·h/mL; AUC(0∞) 5.26±4.35 and 10.98±4.10 μg/mL·h; Cmin,ss 0.03±0.08 and 0.05±0.07 μg/mL; t1/2 1.72±0.78 and 1.80±0.64 h; and Tmax 0.52±0.04 and 0.50±0.00 h. After the first day of treatment, the both groups had (38.6±20.9)% and (46.9±16.5)%, respectively of time with gastric juice pH>4, and (25.5±20.6)% and (32.7±7.9)% respectively with pH>6. In 5 d after the administration, the time percentage of gastric juice pH>4 was (69.6±15.4)% and (80.2±16.6)%, respectively, and it of pH>6 was (48.3±13.7)% and (49.7±15.7)%, respectively. ConclusionThe pantoprazole sodium for injection is in accordance with the linear pharmacokinetic characteristics in healthy volunteers. Compared with the pharmacodynamic parameters of 2 doses, the inhibitory effect of 80 mg dose group is better than that of 40 mg dose group, and the higher dose is safer. It is recommended of 80 mg q12 h in clinical practice.
 

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更新日期/Last Update: 2018-09-19