Pharmacogenomics‐based Tailored Versus Standard Therapeutic Regimen for Eradication of H. pylori

• Published in: Clinical pharmacology and therapeutics 2007-04, Vol.81 (4), p.521-528
• Main Authors: Furuta, T, Shirai, N, Kodaira, M, Sugimoto, M, Nogaki, A, Kuriyama, S, Iwaizumi, M, Yamade, M, Terakawa, I, Ohashi, K, Ishizaki, T, Hishida, A
• Format: Article
• Language: English
• Subjects: 2-Pyridinylmethylsulfinylbenzimidazoles - pharmacokinetics; Adult; Anti-Bacterial Agents - administration & dosage; Anti-Bacterial Agents - pharmacokinetics; Anti-Bacterial Agents - therapeutic use; Anti-Ulcer Agents - pharmacokinetics; Aryl Hydrocarbon Hydroxylases - genetics; Aryl Hydrocarbon Hydroxylases - metabolism; Biological and medical sciences; Clarithromycin - administration & dosage; Clarithromycin - pharmacokinetics; Clarithromycin - therapeutic use; Costs and Cost Analysis; Cytochrome P-450 CYP2C19; Female; Helicobacter Infections - drug therapy; Helicobacter Infections - genetics; Helicobacter Infections - microbiology; Helicobacter pylori; Humans; Lansoprazole; Male; Medical sciences; Mixed Function Oxygenases - genetics; Mixed Function Oxygenases - metabolism; Pharmacogenetics; Pharmacology. Drug treatments; Polymorphism, Genetic - genetics; RNA, Ribosomal - biosynthesis; RNA, Ribosomal - genetics
• ISSN: 0009-9236; 1532-6535
• DOI: 10.1038/sj.clpt.6100043

Helicobacter pylori eradication rates by triple therapy with a proton pump inhibitor, amoxicillin, and clarithromycin at standard doses depend on bacterial susceptibility to clarithromycin and patient CYP2C19 genotypes. We examined the usefulness of a personalized therapy for H. pylori infection based on these factors as determined by genetic testing. First, optimal lansoprazole dosing schedules that would achieve sufficient acid inhibition to allow H. pylori eradication therapy in each of different CYP2C19 genotype groups were determined by a 24‐h intragastric pH monitoring. Next, 300 H. pylori‐positive patients were randomly assigned to the standard regimen group (lansoprazole 30 mg twice daily (b.i.d.)), clarithromycin 400 mg b.i.d., and amoxicillin 750 mg b.i.d. for 1 week) or the tailored regimen group based on CYP2C19 status and bacterial susceptibility to clarithromycin assessed by genetic testing. Patients with failure of eradication underwent the second‐line regimen. The per‐patient cost required for successful eradication was calculated for each of the groups. In the first‐line therapy, the intention‐to‐treat eradication rate in the tailored regimen group was 96.0% (95% CI=91.5–98.2%, 144/150), significantly higher than that in the standard regimen group (70.0%: 95% CI=62.2–77.2%, 105/150) (P