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.
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.
Authors: I Ieiri; Y Kishimoto; H Okochi; K Momiyama; T Morita; M Kitano; T Morisawa; Y Fukushima; K Nakagawa; J Hasegawa; K Otsubo; T Ishizaki Journal: Eur J Clin Pharmacol Date: 2001-09 Impact factor: 2.953
Authors: Sarah C Sim; Carl Risinger; Marja-Liisa Dahl; Eleni Aklillu; Magnus Christensen; Leif Bertilsson; Magnus Ingelman-Sundberg Journal: Clin Pharmacol Ther Date: 2006-01 Impact factor: 6.875
Authors: G N Tytgat; K McColl; J Tack; G Holtmann; R H Hunt; P Malfertheiner; A P S Hungin; H K Batchelor Journal: Aliment Pharmacol Ther Date: 2007-10-31 Impact factor: 8.171
Authors: M Kimura; S Tani; H Watanabe; Y Naito; T Sakusabe; H Watanabe; J Nakaya; F Sasaki; T Numano; T Furuta; T Furuta Journal: Methods Inf Med Date: 2008-11-20 Impact factor: 2.176
Authors: P H O'Donnell; N Wadhwa; K Danahey; B A Borden; S M Lee; J P Hall; C Klammer; S Hussain; M Siegler; M J Sorrentino; A M Davis; Y A Sacro; R Nanda; T S Polonsky; J L Koyner; D L Burnet; K Lipstreuer; D T Rubin; C Mulcahy; M E Strek; W Harper; A S Cifu; B Polite; L Patrick-Miller; K-Tj Yeo; Eky Leung; S L Volchenboum; R B Altman; O I Olopade; W M Stadler; D O Meltzer; M J Ratain Journal: Clin Pharmacol Ther Date: 2017-06-15 Impact factor: 6.875