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


CONCLUSIONS
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.
Furuta
Takahisa
T
Center for Clinical Research, Hamamatsu University School of Medicine, 1-20-1, Handayama, Higashi-Ku, Hamamatsu, 431-3192, Japan. furuta@hama-med.ac.jp
Sugimoto
Mitsushige
M
Kodaira
Chise
C
Nishino
Masafumi
M
Yamade
Mihoko
M
Ikuma
Mutsuhiro
M
Shirai
Naohito
N
Watanabe
Hiroshi
H
Umemura
Kazuo
K
Kimura
Michio
M
Hishida
Akira
A
D053799:2-Pyridinylmethylsulfinylbenzimidazoles / Q000627:therapeutic use*; D000368:Aged; D000897:Anti-Ulcer Agents / Q000627:therapeutic use*; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics* / Q000378:metabolism; D002986:Clinical Trials as Topic; D065731:Cytochrome P-450 CYP2C19; D004305:Dose-Response Relationship, Drug; D005260:Female; D005764:Gastroesophageal Reflux / Q000188:drug therapy* / Q000235:genetics*; D005838:Genotype; D006801:Humans; D064747:Lansoprazole; D008297:Male; D008875:Middle Aged; D017410:Practice Guidelines as Topic / Q000592:standards; D012008:Recurrence
D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D000897:Anti-Ulcer Agents; D064747:Lansoprazole; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19