Double-dosed pantoprazole accelerates the sustained symptomatic response in overweight and obese patients with reflux esophagitis in Los Angeles grades A and B.
OBJECTIVE
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 (P=0.005) until week 8 (P=0.01). While using standard-dosed pantoprazole, PMs had better rates of SSR during the 8-week period than both HomoEMs and HeteroEMs (P<0.05). By using double-dosed pantoprazole, the cumulative rates of SSR were improved as early as week 4 for both HomoEMs and HeteroEMs (P<0.005, 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.
Chen
Wei-Ying
WY
Department of Internal Medicine, National Cheng Kung University Medical Center, Tainan, Taiwan.
Chang
Wei-Lun
WL
Tsai
Yu-Ching
YC
Cheng
Hsiu-Chi
HC
Lu
Cheng-Chan
CC
Sheu
Bor-Shyang
BS
D053799:2-Pyridinylmethylsulfinylbenzimidazoles / Q000008:administration & dosage*; D000328:Adult; D000368:Aged; D015992:Body Mass Index; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004942:Esophagitis, Peptic / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy*; D005260:Female; D005500:Follow-Up Studies; D005764:Gastroesophageal Reflux / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy; D006801:Humans; D053208:Kaplan-Meier Estimate; D015141:Los Angeles; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000150:complications / Q000175:diagnosis; D050177:Overweight / Q000150:complications / Q000175:diagnosis*; D000077402:Pantoprazole; D011336:Probability; D011446:Prospective Studies; D018570:Risk Assessment; D012720:Severity of Illness Index; D018709:Statistics, Nonparametric; D016896:Treatment Outcome
D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D000077402:Pantoprazole