Randomized open trial for comparison of proton pump inhibitors in triple therapy for <i>Helicobacter pylori</i> infection in relation to <i>CYP2C19</i> genotype

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<jats:p><jats:bold>Abstract</jats:bold><jats:bold> <jats:italic>Background and aims</jats:italic> :</jats:bold> Genetic polymorphism of cytochrome <jats:italic>P450</jats:italic> (<jats:italic>CYP</jats:italic>) <jats:italic>2C19</jats:italic> influences the efficacy of <jats:italic>Helicobacter pylori</jats:italic> eradication therapy with a proton pump inhibitor (PPI) and amoxicillin. However, in triple therapy (PPI plus amoxicillin and clarithromycin), little is known about the impact of <jats:italic>CYP2C19</jats:italic> polymorphism, or the use of rabeprazole, which is not well metabolized by <jats:italic>CYP2C19</jats:italic>. The efficacy of three PPI (omeprazole, lansoprazole, and rabeprazole) in a 1‐week triple regimen were compared in relation to <jats:italic>CYP2C19</jats:italic> polymorphism.</jats:p><jats:p><jats:bold> <jats:italic>Method</jats:italic> : </jats:bold> One hundred and eighty‐three patients were randomized to receive one of the following regimens: amoxicillin 500 mg t.i.d., clarithromycin 200 mg t.i.d., and PPI (omeprazole 20 mg, lansoprazole 30 mg, or rabeprazole 10 mg) b.i.d. <jats:italic>CYP2C19</jats:italic> polymorphism was analyzed by PCR restriction fragment length polymorphism.</jats:p><jats:p><jats:bold> <jats:italic>Results</jats:italic> :</jats:bold> Intention‐to‐treat‐based overall cure rates for omeprazole, lansoprazole or rabeprazole regimens were 83.1% (95% confidence interval (CI): 69–89%), 86.7% (CI: 75–93%), and 76.6% (CI: 64–85%), respectively, without significant difference. The cure rate of the rabeprazole regimen (but not the lansoprazole or omeprazole regimens) tended to be correlated with <jats:italic>CYP2C19</jats:italic> genotypes (<jats:italic>P</jats:italic> = 0.076). In patients with a homozygous extensive metabolizer genotype, the per protocol‐based cure rate with rabeprazole (62.5%) was significantly lower than that with lansoprazole (90.0%; <jats:italic>P</jats:italic> = 0.038).</jats:p><jats:p><jats:bold> <jats:italic>Conclusion</jats:italic> :</jats:bold> The overall cure rate of 1‐week triple therapy for <jats:italic>H. pylori</jats:italic> eradication was not significantly different between regimens with omeprazole, lansoprazole or rabeprazole, but the impact of <jats:italic>CYP2C19</jats:italic> genetic polymorphism on the cure rate appeared to differ between these PPI.</jats:p><jats:p>© 2002 Blackwell Publishing Asia Pty Ltd</jats:p>

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