Controlling on-demand gastric acidity in obese subjects: a randomized, controlled trial comparing a single dose of 20 mg rabeprazole and 20 mg omeprazole.

Kafia Belhocine,Fabienne Vavasseur,Christelle Volteau,Yann Touchefeu,Stanislas Bruley Des Varannes,Laurent Flet

doi:10.1186/1471-230x-14-128

Abstract

BackgroundObesity is associated with a risk of gastroesophageal reflux disease. The pharmacodynamic efficacy of proton pump inhibitors has not been specifically evaluated in obese subjects. The aim of this study was to compare the antisecretory response to a single oral dose of 20 mg rabeprazole, 20 mg omeprazole and placebo in obese subjects.MethodsGastric pH was monitored for 24 hours on three separate occasions in eighteen H. pylori-negative, asymptomatic obese subjects. Subjects were given omeprazole, rabeprazole or placebo in a randomized order and in a double-blind fashion. The main analysis criterion was 24-h percent of time post dose with intragastric pH above 3; secondary criteria were percentage of time above pH 4, median pH, [H+] concentrations and nocturnal acid breakthrough (NAB). Results were analyzed using linear mixed models and Wilks test comparing variances.Results24-h median [IQ] percentages of time with gastric pH above 3 and 4 were higher with rabeprazole than omeprazole (46 [37–55] vs. 30 [15–55] %, 9 [5-11] % for placebo) but the differences did not reach statistical significance (p = 0.11 and 0.24, respectively). Median acid concentrations were significantly lower with rabeprazole than with omeprazole and placebo (22 [14–53] vs. 54 [19–130] and 95 [73–170] mmoles/l, p < 0.01) for all periods. The number of NAB was significantly lower with rabeprazole than with omeprazole (median 1 [1,2] vs. 2 [1-3], p = 0.04). Variances of 24-h data (pH above 3 and 4, median pH, [H+] concentrations) were significantly lower with rabeprazole than with omeprazole (p < 0.0001).ConclusionsIn asymptomatic obese subjects the gastric antisecretory response to a single dose of rabeprazole and omeprazole was strong and not significantly different between drugs despite a significantly more homogeneous response with rabeprazole.Trial registrationClinicalTrial.gov: NCT01136317

Highlights

Obesity is associated with a risk of gastroesophageal reflux disease
No study has established whether high body mass index (BMI) might affect the pharmacodynamic and pharmacokinetic profile of Proton pump inhibitor (PPI) [4]
As most PPIs are mainly metabolized by the liver cytochrome P450 (CYP450) pathway [8], metabolism may be affected in the setting of obesity with fatty liver disease

Summary

Introduction

Obesity is associated with a risk of gastroesophageal reflux disease. GERD is a multifactorial disease, being overweight and obese are established as increasing the risk of developing GERD and its complications [2]. In overweight and obese subjects, direct mechanical factors and proinflammatory signals derived from the visceral adipose tissue may account for an increased occurrence of reflux episodes [3]. Some studies have reported a lower rate of healing of esophagitis symptoms control in patients with a high BMI treated with esomeprazole [9,10]. Another study using a retrospective design did not find any clear differences in mucosal healing rate between lean and overweight/obese patients treated with omeprazole or rabeprazole [12]

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