title: On-demand proton pump inhibitory treatment in overweight/obese patients with gastroesophageal reflux disease: are there pharmacodynamic arguments for using higher doses?
abstract: BACKGROUND
  Increased body mass index (BMI) is associated with a higher risk of gastroesophageal reflux disease (GORD).
  
  
  OBJECTIVE
  To investigate whether overweight/obesity affects proton pump inhibitor pharmacodynamics when used in a single dose in patients with GORD.
  
  
  METHODS
  Post hoc analyses by patient BMI were performed on data from two single-center, double-blind, single-dose, crossover studies comparing the pharmacodynamics of rabeprazole 20 mg and pantoprazole 40 mg in GORD patients with a history of nocturnal heartburn. The primary endpoint was the mean percentage of time with intragastric pH >4 between lean and overweight/obese patients (BMI <25 and ≥25).
  
  
  RESULTS
  24 h baseline intragastric pH values were not different between BMI groups. The pharmacodynamic effects of both proton pump inhibitors were not significantly different between BMI groups, and no evidence was found for an interaction between BMI and treatment. As compared with pantoprazole, rabeprazole showed a significantly greater effect on the antisecretory response for both BMI groups.
  
  
  CONCLUSIONS
  Overweight/obesity in GORD patients does not appear to affect the antisecretory efficacy of a single dose of rabeprazole and pantoprazole. These data do not support adapting the dosage of rabeprazole and pantoprazole according to BMI in GORD patients when administered as an on-demand therapy schedule.
authors.affiliation: Nantes University Hospital, INSERM-U913, Institut des Maladies de l'Appareil Digestif (IMAD), Nantes, France. stanislas.bruleydesvarannes@chu-nantes.fr
authors.forename: Stanislas
authors.initials: S
authors.lastname: Bruley des Varannes
authors.forename: Bogdana
authors.initials: B
authors.lastname: Coudsy
authors.forename: Sandra
authors.initials: S
authors.lastname: Waechter
authors.forename: Byron
authors.initials: B
authors.lastname: Delemos
authors.forename: Jim
authors.initials: J
authors.lastname: Xiang
authors.forename: John
authors.initials: J
authors.lastname: Lococo
authors.forename: Philippe
authors.initials: P
authors.lastname: Ducrotté
mesh_terms: D053799:2-Pyridinylmethylsulfinylbenzimidazoles / Q000008:administration & dosage* / Q000493:pharmacokinetics; D000293:Adolescent; D000328:Adult; D000368:Aged; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005260:Female; D005764:Gastroesophageal Reflux / Q000188:drug therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000188:drug therapy*; D050177:Overweight / Q000188:drug therapy*; D000077402:Pantoprazole; D054328:Proton Pump Inhibitors / Q000008:administration & dosage* / Q000493:pharmacokinetics; D064750:Rabeprazole / Q000008:administration & dosage* / Q000493:pharmacokinetics; D055815:Young Adult
chemical_list: D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D054328:Proton Pump Inhibitors; D064750:Rabeprazole; D000077402:Pantoprazole