CYP2C19基因分型在基于雷贝拉唑的短期幽门螺杆菌三联疗法中的药代动力学-药效学分析

Pharmacokinetic- pharmacodynamic analysis of the role of CYP2C19 genotypes in short-term rabeprazole-based triple therapy against Helicobacter pylori.

作者信息

Yang Jyh-Chin, Yang Yu-Fan, Uang Yow-Shieng, Lin Chun-Jung, Wang Teh-Hong

机构信息

Department of Internal Medicine, Hospital and College of Medicine, National Taiwan University, Taipei, Taiwan.

出版信息

Br J Clin Pharmacol. 2009 May;67(5):503-10. doi: 10.1111/j.1365-2125.2009.03393.x. Epub 2009 Feb 23.

DOI:10.1111/j.1365-2125.2009.03393.x

PMID:19552744

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2686066/

Abstract

AIMS

The aim was to explore the role of CYP2C19 polymorphism in short-term rabeprazole-based triple therapy against Helicobacter pylori infection.

METHODS

Patients with H. pylori infection were tested for CYP2C19 genotype as poor metabolizers (PMs) or extensive metabolizers (EMs, homozygous EM or heterozygous EM) and given rabeprazole for 7 days. Antibiotics (clarithromycin and amoxicillin) were given on days 1-4, days 4-7, or days 1-7. A direct link model with an effect compartment was used in the population pharmacokinetic-pharmacodynamic analysis. The status of H. pylori infection was evaluated.

RESULTS

Rabeprazole clearance was lower in CYP2C19 PMs than in EMs (with average values of 10.7 vs. 16.8 l h(-1) in PMs and EMs, respectively), resulting in higher plasma levels in the former group. The values of EC(50) and k(eo) of gastrin response increased with multiple doses of rabeprazole. The k(eo) values were lower in CYP2C19 PMs than in EMs on day 1 (0.012 vs. 0.017 x 10(-4) l min(-1)), and higher than in EMs on day 4 (0.804 vs. 0.169 x 10(-4) l min(-1)) of rabeprazole treatment. The predicted gastrin-time profile showed a higher response in CYP2C19 PMs than in EMs on days 4 and 7. Helicobacter pylori was eradicated in all CYP2C19 PMs except in one patient infected by a resistant strain. In contrast, in CYP2C19 EMs the eradication rates ranged from 58 to 85%.

CONCLUSIONS

CYP2C19 genotypes play a role in H. pylori eradication therapy. Rabeprazole-based short-term triple therapy may be applicable in CYP2C19 PMs for H. pylori eradication.

摘要

目的

探讨细胞色素P450 2C19（CYP2C19）基因多态性在基于雷贝拉唑的短期三联疗法根除幽门螺杆菌感染中的作用。

方法

对幽门螺杆菌感染患者进行CYP2C19基因分型检测，分为慢代谢型（PMs）或快代谢型（EMs，纯合子EM或杂合子EM），给予雷贝拉唑治疗7天。抗生素（克拉霉素和阿莫西林）在第1 - 4天、第4 - 7天或第1 - 7天给予。群体药代动力学 - 药效学分析采用带有效应室的直接联系模型。评估幽门螺杆菌感染状况。

结果

CYP2C19 PMs中雷贝拉唑清除率低于EMs（PMs和EMs的平均值分别为10.7与16.8 l h⁻¹），导致前一组血浆水平更高。胃泌素反应的半数效应浓度（EC₅₀）和效应室药物消除速率常数（kₑₒ）值随雷贝拉唑多剂量给药而增加。在雷贝拉唑治疗第1天，CYP2C19 PMs的kₑₒ值低于EMs（0.012 vs. 0.017×10⁻⁴ l min⁻¹），而在第4天高于EMs（0.804 vs. 0.169×10⁻⁴ l min⁻¹）。预测的胃泌素 - 时间曲线显示，在第4天和第7天，CYP2C19 PMs的反应高于EMs。除1例感染耐药菌株的患者外，所有CYP2C19 PMs中的幽门螺杆菌均被根除。相比之下，在CYP2C19 EMs中，根除率为58%至85%。