Pharmacokinetic– pharmacodynamic analysis of the role of CYP2C19 genotypes in short‐term rabeprazole‐based triple therapy againstHelicobacter pylori

作者：Jyh‐Chin Yang, Yufan Yang, Yow‐Shieng Uang, Chun‐Jung Lin, Teh‐Hong Wang · 发表于：British Journal of Clinical Pharmacology · 年份：2009 · DOI：10.1111/j.1365-2125.2009.03393.x · 被引用次数：17 · 研究领域：Helicobacter pylori-related gastroenterology studies、Pharmacogenetics and Drug Metabolism、Inflammatory Bowel Disease

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • Asians have a higher percentage of CYP2C19 poor metabolizers (PMs) and a high percentage of Helicobacter pylori infection compared with Whites. • Although rabeprazole has been suggested to be least affected by CYP2C19 genotype, the pharmacokinetic properties of rabeprazole have been shown to correlate with the CYP2C19 genotype. • Short‐term (i.e. <7 days) rabeprazole‐based triple therapy has been suggested for its use in eradicating H. pylori , whereas the eradication rate has been reported variously as 90–27% without CYP2C19 genotyping. WHAT THIS STUDY ADDS • Population pharmacokinetic–pharmacodynamic analysis showed that the plasma rabeprazole levels, the values of k eo (the first‐order rate constant for drug dissipation from the effect compartment), and the predicted gastrin‐time profile were higher in CYP2C19 PMs than in extensive metabolizers (EMs) after multiple dosing. • Helicobacter pylori was eradicated in all CYP2C19 PMs except in one patient infected by a resistant strain, whereas the eradication rates ranged from 58 to 85% in CYP2C19 EMs. 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 amoxic...