CYP2C19 genotype is associated with symptomatic recurrence of GERD during maintenance therapy with low-dose lansoprazole.

BACKGROUND/AIMS: Maintenance therapy of gastroesophageal reflux disease (GERD) is usually performed with a low dose of a proton-pump inhibitor (PPI). Because PPIs are metabolized by CYP2C19 in the liver, we investigated whether a patient's CYP2C19 genotype was associated with symptomatic recurrence...

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Publicado en:European Journal of Clinical Pharmacology Vol. 65; no. 7; pp. 693 - 699
Autores principales: Furuta T, Sugimoto M, Kodaira C, Nishino M, Yamade M, Ikuma M, Shirai N, Watanabe H, Umemura K, Kimura M, Hishida A
Formato: research Journal Article
Publicado: Springer Nature Jul2009
Acceso en línea:Ver este registro en EBSCOhost
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      dt: Jul2009
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      pub: Springer Nature
      place: New York, New York
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        10.1007/s00228-009-0628-5
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        atl: CYP2C19 genotype is associated with symptomatic recurrence of GERD during maintenance therapy with low-dose lansoprazole.
      aug:
        au:
          Furuta T
          Sugimoto M
          Kodaira C
          Nishino M
          Yamade M
          Ikuma M
          Shirai N
          Watanabe H
          Umemura K
          Kimura M
          Hishida A
        affil: Center for Clinical Research, Hamamatsu University School of Medicine, 1-20-1, Handayama, Higashi-Ku, Hamamatsu, 431-3192, Japan. furuta@hama-med.ac.jp
      sug:
        subj:
          Gastroesophageal Reflux Therapy
          Genotype
          Lansoprazole Pharmacokinetics
          Oxidoreductases Physiology
          Recurrence Evaluation
          Cox Proportional Hazards Model
          Descriptive Statistics
          Female
          Funding Source
          Male
          Middle Age
          Pharmacy and Pharmacology
          Urease
          Human
          Middle Aged: 45-64 years
          Female
          Male
      ab: BACKGROUND/AIMS: Maintenance therapy of gastroesophageal reflux disease (GERD) is usually performed with a low dose of a proton-pump inhibitor (PPI). Because PPIs are metabolized by CYP2C19 in the liver, we investigated whether a patient's CYP2C19 genotype was associated with symptomatic recurrence of GERD during maintenance therapy with a low dose of a PPI. METHODS: We enrolled 124 patients with erosive GERD whose esophageal mucosal breaks were endoscopically proven to be cured after treatment with lansoprazole 30 mg/day for 8 weeks. When reflux symptoms occurred less than once per week, the dose of lansoprazole was decreased to 15 mg/day, but if symptoms then occurred more than once per week, it was restored to 30 mg/day. CYP2C19 genotypes were classified as rapid metabolizer (RM), intermediate metabolizer (IM) or poor metabolizer (PM). RESULTS: In 18 of 54 RMs, 28 of 56 IMs, and 8 of 14 PMs, the maintenance dose of lansoprazole was decreased to 15 mg/day, but in 16 (88.9%), 22 (78.6%), and 4 (50%), respectively, there was symptomatic recurrence of GERD and the dose was restored to 30 mg/day. The hazard ratios of symptomatic recurrence of GERD in IMs and PMs compared with RMs were 0.40 (95%CI: 0.19-0.87, P = 0.021) and 0.19 (95%CI: 0.05-0.69, P = 0.011). CONCLUSION: When the dose of lansoprazole is decreased, the RM genotype of CYP2C19 appears to be a risk factor for symptomatic recurrence of GERD. The CYP2C19 genotyping test would be useful for determining the optimal dose of a PPI for maintenance therapy of GERD.
      pubtype: Academic Journal
      doctype:
        research
        Journal Article
      ougenre: Article
    language: English
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