OBJECTIVES: Body mass index (BMI) in the range defined as overweight or obese adversely decreases the sustained symptomatic response (SSR) to proton pump inhibitors for patients with reflux esophagitis of Los Angeles grade A or B (RE-AB). We thus investigated whether double-dosed pantoprazole can accelerate SSR in such patients.METHODS: A total of 200 overweight or obese patients with RE-AB were evenly randomized into a double-dosed group (receiving 8-week pantoprazole 40 mg twice daily) or a standard-dosed control group (receiving 8-week pantoprazole 40 mg per day and one blank tablet at night). In each patient, demographic factors and the genotype of S-mephenytoin 4′-hydroxylase (CYP2C19) were checked and defined as poor metabolizer (PM), or homologous extensive metabolizer (HomoEM), or heterologous extensive metabolizer (HeteroEM). The cumulative proportions of patients with SSR were compared during the 8-week period.RESULTS: Both intention-to-treat and per-protocol analyses disclosed that the rates of SSR were higher in the double-dosed group than in the standard-dosed group from week 4 (P0.005) until week 8 (P0.01). While using standard-dosed pantoprazole, PMs had better rates of SSR during the 8-week period than both HomoEMs and HeteroEMs (P0.05). By using double-dosed pantoprazole, the cumulative rates of SSR were improved as early as week 4 for both HomoEMs and HeteroEMs (P0.005, log-rank test).CONCLUSIONS: For RE-AB in overweight and obese patients, double-dosed pantoprazole effectively accelerates the SSR, especially for those with CYP2C19 genotypes as HeteroEM or HomoEM. Accordingly, it offers an earlier shift into on-demand pantoprazole for RE-AB patients with high BMI.
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