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用 13C-泮托拉唑呼气试验预测 CYP2C19 表型和质子泵抑制剂兰索拉唑的疗效。

[13C]-pantoprazole breath test to predict CYP2C19 phenotype and efficacy of a proton pump inhibitor, lansoprazole.

机构信息

Center for Clinical Research, Hamamatsu University School of Medicine, Hamamatsu, Japan.

出版信息

Aliment Pharmacol Ther. 2009 Aug;30(3):294-300. doi: 10.1111/j.1365-2036.2009.04044.x. Epub 2009 May 18.

Abstract

BACKGROUND

(13)CO(2) is produced on metabolism of (13)C-labelled-pantoprazole ([(13)C]-pantoprazole) by CYP2C19.

AIM

To investigate whether the [(13)C]-pantoprazole breath test can predict CYP2C19 status and efficacy of proton pump inhibitors (PPIs) in Japanese.

METHODS

We classified 110 healthy volunteers as rapid metabolizers (RM), intermediate metabolizers (IM) or poor metabolizers (PM) of CYP2C19 by genotyping. Breath samples were collected at 10-min intervals for 60 min after dosing with 100 mg [(13)C]-pantoprazole. Changes in the carbon isotope ratios ((13)CO(2)/(12)CO(2)) in carbon dioxide in breath samples were measured and expressed as a delta-over-baseline (DOB) ratio ( per thousand). Of the 110 subjects, twenty-two randomly selected subjects underwent intragastric pH monitoring on day 7 of dosing with 30 mg of lansoprazole.

RESULTS

The DOB values of RMs were the highest and those of PMs the lowest of the three groups. Statistically significant differences were observed in the area-under-the-curve (AUC)(20-60 min) of DOB among the three groups. The mean 24-h intragastric pHs attained by lansoprazole 30 mg for 7 days were inversely correlated with the AUC(20-60 min) of DOB.

CONCLUSIONS

[(13)C]-pantoprazole breath test can easily estimate the individual activity of CYP2C19 and predict the efficacy of a PPI (i.e. lansoprazole). This test would be useful for individualized medicine with a PPI.

摘要

背景

(13)CO2 是由 CYP2C19 代谢(13C 标记的泮托拉唑)[(13)C]-泮托拉唑产生的。

目的

研究(13)C-泮托拉唑呼气试验能否预测 CYP2C19 状态和质子泵抑制剂(PPIs)在日本人中的疗效。

方法

我们通过基因分型将 110 名健康志愿者分为 CYP2C19 快速代谢者(RM)、中间代谢者(IM)或弱代谢者(PM)。给药后 10 分钟收集 60 分钟的呼吸样本[(13)C]-泮托拉唑 100mg。测量呼气样本中二氧化碳中碳同位素比((13)CO2/(12)CO2)的变化,并表示为基线(DOB)比值(每千分之一)。在 110 名受试者中,随机选择 22 名受试者在给药第 7 天接受 30mg 兰索拉唑进行胃内 pH 监测。

结果

RM 的 DOB 值最高,PM 的 DOB 值最低。三组之间 DOB 值的曲线下面积(AUC)(20-60 分钟)存在显著差异。兰索拉唑 30mg 7 天的平均 24 小时胃内 pH 值与 DOB AUC(20-60 分钟)呈负相关。

结论

(13)C-泮托拉唑呼气试验可简便地估计 CYP2C19 的个体活性,预测 PPI(即兰索拉唑)的疗效。该试验对于个体化 PPI 治疗具有重要意义。

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