Pharmacokinetic– pharmacodynamic analysis of the role of CYP2C19 genotypes in short-term rabeprazole-based triple therapy against Helicobacter pylori |
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Authors: | Jyh-Chin Yang,Yu-Fan Yang,Yow-Shieng Uang,Chun-Jung Lin,& Teh-Hong Wang |
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Affiliation: | Department of Internal Medicine, Hospital and College of Medicine, School of Pharmacy, College of Medicine, National Taiwan University and;School of Pharmacy, Taipei Medical University, Taipei, Taiwan |
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Abstract: | AIMSThe aim was to explore the role of CYP2C19 polymorphism in short-term rabeprazole-based triple therapy against Helicobacter pylori infection.METHODSPatients 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.RESULTSRabeprazole 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 EC50 and keo of gastrin response increased with multiple doses of rabeprazole. The keo values were lower in CYP2C19 PMs than in EMs on day 1 (0.012 vs. 0.017 × 10−4 l min−1), and higher than in EMs on day 4 (0.804 vs. 0.169 × 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%.CONCLUSIONSCYP2C19 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. |
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Keywords: | CYP2C19 polymorphism Helicobacter pylori population PK/PD rabeprazole |
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