Effect of omeprazole 10 mg on intragastric pH in three different CYP2C19 genotypes, compared with omeprazole 20 mg and lafutidine 20 mg, a new H2-receptor antagonist

Aliment Pharmacol Ther. 2003 Dec;18(11-12):1149-57. doi: 10.1046/j.1365-2036.2003.01804.x.

Abstract

Background: Omeprazole 10 mg is used as maintenance therapy for gastro-oesophageal reflux disease, but previous reports have not mentioned the potency of its acid suppression.

Aim: To evaluate the potency of acid suppression with omeprazole 10 mg, in relation to CYP2C19 genotypes.

Methods: Eighteen healthy subjects without Helicobacter pylori participated. After a 7-day regimen of omeprazole 10 mg, 20 mg, lafutidine 20 mg (a novel H2-receptor antagonist) or water only (baseline data), intragastric pH was measured for 24 h.

Results: With omeprazole 10 mg, greater differences were observed than 20 mg in median pH values and pH > 4 holding time ratios between poor metabolizers (PMs, n = 6) and the others [homozygous extensive metabolizers (homo-EMs, n = 6) and heterozygous extensive metabolizers (hetero-EMs, n = 6)]. With lafutidine 20 mg, these parameters were not influenced by the genotype. The potency of acid suppression was: omeprazole 20 mg approximately lafutidine 20 mg > omeprazole 10 mg in homo-EMs, omeprazole 20 mg > omeprazole 10 mg approximately lafutidine 20 mg in hetero-EMs, and omeprazole 20 mg approximately omeprazole 10 mg > lafutidine 20 mg in PMs.

Conclusions: Omeprazole 10 mg strongly suppresses acid secretion, but depending on the CYP2C19 genotypes shows greater interindividual variations in suppression than 20 mg.

Publication types

  • Clinical Trial
  • Comparative Study
  • Randomized Controlled Trial

MeSH terms

  • Acetamides / administration & dosage*
  • Acetamides / pharmacology
  • Adult
  • Aryl Hydrocarbon Hydroxylases / genetics
  • Circadian Rhythm
  • Cross-Over Studies
  • Cytochrome P-450 CYP2C19
  • Gastric Acid / physiology*
  • Gastric Acidity Determination
  • Genotype
  • Humans
  • Hydrogen-Ion Concentration
  • Male
  • Manometry
  • Mixed Function Oxygenases / genetics
  • Omeprazole / pharmacology*
  • Piperidines / administration & dosage*
  • Piperidines / pharmacology
  • Prospective Studies
  • Pyridines / administration & dosage*
  • Pyridines / pharmacology
  • Receptors, Histamine H2 / administration & dosage*
  • Receptors, Histamine H2 / physiology

Substances

  • Acetamides
  • Piperidines
  • Pyridines
  • Receptors, Histamine H2
  • lafutidine
  • Mixed Function Oxygenases
  • Aryl Hydrocarbon Hydroxylases
  • CYP2C19 protein, human
  • Cytochrome P-450 CYP2C19
  • Omeprazole