Effects of different omeprazole dosing on gastric pH in non-variceal upper gastrointestinal bleeding: A randomized prospective study

J Dig Dis. 2016 Sep;17(9):588-599. doi: 10.1111/1751-2980.12393.

Abstract

Objective: We aimed to identify the best method of omeprazole (OME) application with respect to intragastric pH, cytochrome P450 2C19 (CYP2C19) genotype and phenotype.

Methods: The patients with non-variceal upper gastrointestinal bleeding (NVUGIB) were prospectively enrolled. After the achievement of endoscopic hemostasis, the patients were randomized to 40-mg intravenous (i.v.) OME bolus injection every 12 h or 8-mg/h continuous i.v. infusion for 72 h after an 80-mg i.v. OME bolus administration. The intragastric pH was recorded for 72 h. The CYP2C19 variant alleles (*2, *3, *17) were analyzed and the serum concentrations of OME and 5-hydroxyomeprazole (5-OH OME) were determined.

Results: Altogether 41 Caucasians (18 in the OME infusion [OI] group and 23 in the OME bolus [OB] group) were analyzed. The median percentage of time with an intragastric pH > 4.0 was higher in the infusion group than in the OB group over 48 h (100% vs 96.6%, P = 0.009) and 72 h (100% vs 87.6%, P = 0.006), and that at an intragastric pH >6.0 was higher in the OI group than the OB group over 72 h (97.9% vs 63.5%, P = 0.04). Helicobacter pylori infection was correlated with the fastest increase in intragastric pH, especially in the OI group. In both groups, CYP2C19 genotypes (*1/*1, *1/*17, *17/*17) had no essential effect on intragastric pH.

Conclusions: In patients with NVUGIB, OME i.v. bolus followed by continuous infusion is more effective than OME i.v. bolus every 12 h in maintaining higher intragastric pH, regardless of CYP2C19 genetic polymorphisms. H. pylori infection accelerates the initial elevation of intragastric pH.

Keywords: CYP2C19; Helicobacter pylori; intragastric pH; non-variceal upper gastrointestinal bleeding; proton pump inhibitor.

Publication types

  • Comparative Study
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Cytochrome P-450 CYP2C19 / genetics
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • Duodenal Ulcer / blood
  • Duodenal Ulcer / drug therapy
  • Duodenal Ulcer / genetics
  • Female
  • Gastric Acid / metabolism
  • Gastric Acidity Determination
  • Genotype
  • Helicobacter Infections / genetics
  • Helicobacter Infections / metabolism
  • Helicobacter pylori
  • Humans
  • Hydrogen-Ion Concentration / drug effects
  • Infusions, Intravenous
  • Injections, Intravenous
  • Male
  • Middle Aged
  • Omeprazole / administration & dosage*
  • Omeprazole / blood
  • Peptic Ulcer Hemorrhage / blood
  • Peptic Ulcer Hemorrhage / drug therapy*
  • Peptic Ulcer Hemorrhage / genetics
  • Prospective Studies
  • Proton Pump Inhibitors / administration & dosage*
  • Proton Pump Inhibitors / blood
  • Stomach Ulcer / blood
  • Stomach Ulcer / drug therapy
  • Stomach Ulcer / genetics
  • Young Adult

Substances

  • Proton Pump Inhibitors
  • CYP2C19 protein, human
  • Cytochrome P-450 CYP2C19
  • Omeprazole