Document Detail


Effect of cytochrome P4502C19 genotypic differences on cure rates for gastroesophageal reflux disease by lansoprazole.
MedLine Citation:
PMID:  12386647     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND AND OBJECTIVES: The acid-inhibitory effect of lansoprazole depends on differences in cytochrome P450 (CYP) 2C19 genotypes. We assessed whether therapeutic effects of lansoprazole on gastroesophageal reflux disease (GERD) depended on the CYP2C19 genotype status in relation to the grade of GERD. METHODS: A total of 65 patients with GERD (grades A-D) completed treatment with lansoprazole, by taking 30 mg orally once a day for 8 weeks. The CYP2C19 genotype status of patients was determined by polymerase chain reaction-restriction fragment length polymorphism analysis. Before and after treatment, esophageal endoscopy was performed. GERD was considered to be cured on the basis of endoscopic findings at the end of treatment. Plasma lansoprazole levels could be determined at 3 hours after the last 30-mg dose of lansoprazole in the 27 genotyped patients. RESULTS: Cure rates for GERD depended significantly on the CYP2C19 genotype status, as well as the grade of GERD before treatment. Cure rates in the homozygous extensive, heterozygous extensive, and poor metabolizer groups were 45.8%, 67.9%, and 84.6%, respectively. Cure rates in the groups with GERD grade A, grade B, and grade C or D were 85.0%, 60.0%, and 45.0%, respectively. The cure rate in patients with the homozygous extensive metabolizer genotype of CYP2C19 with a GERD grade of C or D was very low (16.7%). Plasma lansoprazole levels in patients with the homozygous extensive metabolizer genotype were the lowest of the 3 groups. CONCLUSIONS: CYP2C19 genotype status, as well as the grade of GERD before treatment, is one of the determinants for the success or failure of treatment of GERD with lansoprazole. The low cure rate in patients with the homozygous extensive metabolizer genotype appeared to be a result of these patients having the lowest plasma lansoprazole levels among the 3 genotype groups.
Authors:
Takahisa Furuta; Naohito Shirai; Fumitoshi Watanabe; Satoru Honda; Ken Takeuchi; Takayuki Iida; Yoshihiko Sato; Masayoshi Kajimura; Hajime Futami; Shigekazu Takayanagi; Masami Yamada; Kyoichi Ohashi; Takashi Ishizaki; Hiroyuki Hanai
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Clinical pharmacology and therapeutics     Volume:  72     ISSN:  0009-9236     ISO Abbreviation:  Clin. Pharmacol. Ther.     Publication Date:  2002 Oct 
Date Detail:
Created Date:  2002-10-18     Completed Date:  2002-11-12     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0372741     Medline TA:  Clin Pharmacol Ther     Country:  United States    
Other Details:
Languages:  eng     Pagination:  453-60     Citation Subset:  AIM; IM    
Affiliation:
First Department of Medicine, Hamamatsu University School of Medicine, Japan. furutat@mail,nih.gov
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MeSH Terms
Descriptor/Qualifier:
2-Pyridinylmethylsulfinylbenzimidazoles
Aged
Aryl Hydrocarbon Hydroxylases / genetics*,  metabolism
Confidence Intervals
Female
Gastroesophageal Reflux / classification,  drug therapy*,  enzymology,  genetics*
Genotype
Helicobacter Infections / classification,  drug therapy,  enzymology,  genetics
Helicobacter pylori
Humans
Male
Middle Aged
Mixed Function Oxygenases / genetics*,  metabolism
Odds Ratio
Omeprazole / analogs & derivatives*,  blood,  therapeutic use*
Chemical
Reg. No./Substance:
0/2-Pyridinylmethylsulfinylbenzimidazoles; 103577-45-3/lansoprazole; 73590-58-6/Omeprazole; EC 1.-/Mixed Function Oxygenases; EC 1.14.14.1/Aryl Hydrocarbon Hydroxylases; EC 1.14.14.1/CYP2C19 protein, human

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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