title: Concomitant Administration of a Histamine2 Receptor Antagonist and Proton Pump Inhibitor Enhances Gastric Acid Suppression.
abstract: OBJECTIVE
  Because it has been hypothesized that histamine2 receptor antagonists (H2 RAs) might interfere with the action of proton pump inhibitors (PPIs) when the drugs are given concomitantly, we sought to compare the pharmacodynamic effects of simultaneous administration of a PPI and an H2 RA with the effects of each drug administered alone.
  
  
  METHODS
  Prospective, randomized, double-blind, three-way crossover study.
  
  
  METHODS
  Esophageal motility laboratory at a large teaching hospital.
  
  
  METHODS
  Twenty-one healthy volunteers.
  
  
  METHODS
  Subjects were randomized to one of three treatment arms: an H2 RA (ranitidine 300 mg) plus placebo, a PPI (omeprazole 40 mg) plus placebo, or ranitidine 300 mg plus omeprazole 40 mg, all given once/day at 8 a.m., 30 minutes before a standard breakfast, for 1 week. The subjects then received the other two treatments, with each treatment period separated by a 1-week washout period.
  
  
  RESULTS
  The primary outcome was length of time that the gastric pH remained higher than 4. Secondary outcomes were median gastric pH higher than 4 and percentage of time that the gastric pH remained higher than 4. On day 7, ambulatory intragastric pH was recorded over an 8-hour period in each treatment arm. The combination of ranitidine and omeprazole resulted in a significantly longer time that the gastric pH remained higher than 4 (median 410.5 min [interquartile range (IQR) 298.5-454.25 min]) versus either omeprazole alone (median 356.7 min [IQR 254.9-419.2 min], p=0.023) or ranitidine alone (134.1 min [IQR 99.9-302.5 min], p<0.0001). Median gastric pH was also significantly higher when omeprazole and ranitidine were given in combination (pH 5.92 [IQR 4.75-6.46]) than either omeprazole alone (pH 4.88 [IQR 4.27-6.11], p=0.001) or ranitidine alone (pH 2.31 [IQR 2.04-5.27], p=0.0003). Likewise, the percentage of time that the gastric pH remained higher than 4 was significantly higher when omeprazole and ranitidine were given in combination (median 85.52%) than either omeprazole alone (74.31%, p=0.027) or ranitidine alone (27.94%, p=0.0002).
  
  
  CONCLUSIONS
  When a PPI and H2 RA were administered concomitantly 30 minutes before breakfast, the H2 RA did not decrease the acid suppressive ability of the PPI; rather, it improved gastric acid control. Thus these results failed to support the initial hypothesis of this study. Further prospective studies are needed to test these findings in patients with gastroesophageal reflux disease as well as those with erosive esophagitis.
authors.affiliation: Gastroenterology and Hepatology, Medical University of South Carolina, Charleston, South Carolina.
authors.forename: Mustafa
authors.initials: M
authors.lastname: Abdul-Hussein
authors.affiliation: Gastroenterology and Hepatology, Medical University of South Carolina, Charleston, South Carolina.
authors.forename: Janice
authors.initials: J
authors.lastname: Freeman
authors.affiliation: Gastroenterology and Hepatology, Medical University of South Carolina, Charleston, South Carolina.
authors.forename: Donald
authors.initials: D
authors.lastname: Castell
mesh_terms: D000328:Adult; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D005744:Gastric Acid / Q000378:metabolism*; D005764:Gastroesophageal Reflux / Q000517:prevention & control*; D006635:Histamine H2 Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D008297:Male; D009853:Omeprazole / Q000008:administration & dosage / Q000494:pharmacology*; D011446:Prospective Studies; D054328:Proton Pump Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D011899:Ranitidine / Q000008:administration & dosage / Q000494:pharmacology*; D016896:Treatment Outcome
chemical_list: D006635:Histamine H2 Antagonists; D054328:Proton Pump Inhibitors; D011899:Ranitidine; D009853:Omeprazole
keywords: GERD; H2RA; PPI; concomitant PPI and H2RA; gastric acid; histamine2 receptor antagonist; proton pump inhibitor