Yonago Acta medica 2008;51:31–38
Effect of CYP2C19 Polymorphism on Treatment Success in Lansoprazole-Based 7-Day Treatment Regimen for Cure of H. pylori Infection in Japan
Yosuke Kishimoto*†, Kazuo Yashima‡, Akiko Sano*, Masaharu Koda‡, Tomoyuki Mukoyama‡, Atsushi Yanagidani‡, Akihide Udagawa‡, Koichiro Kawaguchi‡, Takahiro Nomi‡, Atsushi Kitamura‡, Yasuyoshi Fujii‡, Atsushi Tsutsumi‡, Yuji Takano‡, Shuji Kitaoka‡, Norimasa Miura*, Masayuki Kitano¶, Naoto Maeda‡, Akihide Hosoda‡, Goshi Shiota§, Yoshikazu Murawaki‡ and Junichi Hasegawa
Division of Pharmacotherapeutics, Department of Pathophysiological and Therapeutic Science, School of Medicine, Tottori University Faculty of Medicine, Yonago 683-8503, †Department of Internal Medicine, Hitachi General Hospital, Hitachi 317-0077, ‡Division of Medicine and Clinical Science, Department of Multidisciplinary Internal Medicine, School of Medicine, Tottori University Faculty of Medicine, Yonago 683-8504, ¶Division of Gastroenterology and Hepatology, Department of Internal Medicine, Kinki University School of Medicine, Osaka-Sayama 589-8511 and §Division of Molecular and Genetic Medicine, Department of Genetic Medicine and Regenerative Therapeutics, Institute of Regenerative Medicine and Biofunction, Graduate School of Medical Sciences, Tottori University Faculty of Medicine, Yonago 683-8503 Japan
Recently, Helicobacter pylori (H. pylori)-positive peptic ulcer patients were treated by a 1-week triple therapy [lansoprazole (LPZ) 30 mg, amoxicillin 750 mg and clarithromycin 200 or 400 mg, each twice daily] without the checking CYP2C19 genotype in Japan. This regimen was done to obtain sufficient cure rates for H. pylori infection using a high dose of LPZ (60 mg/day) without the great cost of having to determine the genotype. However, the failure rate for eradicating H. pylori was reported to be 12.5%. The reasons for this were studied in 33 Japanese patients with H. pylori-positive gastric or duodenal ulcer. Blood samples of the patients were collected to determine the genotype of CYP2C19 and plasma concentrations of LPZ and its metabolites at 3 h postdose on the morning of the 7th day of treatment. H. pylori infection was cured in 25 of the 33 patients (75.8%). The cure rate was highest in the group of poor metabolizers (PM), intermediate in the group of extensive metabolizers of the heterozygous type (htEM) and lowest in the group of extensive metabolizers of the homozygous type (hmEM). The relative ratio of mean plasma concentration for LPZ among the 3 groups was 1.00:1.43:2.93 (hmEM:htEM:PM groups). Our data suggest that success of the eradication is dependent on the CYP2C19-related genotypic status or the plasma concentrations of LPZ in a steady state condition after a multiple dosing regimen; that is to say, checking CYP2C19 is necessary even on occasions when treatment is done by H. pylori eradication methods as performed in Japan.
Key words: CYP2C19; Helicobacter pylori; Japan; lansoprazole
