Pharmacokinetics and pharmacodynamics of esomeprazole, the S-isomer of omeprazole

Aliment Pharmacol Ther. 2001 Oct;15(10):1563-9. doi: 10.1046/j.1365-2036.2001.01087.x.

Abstract

Background: Esomeprazole, the S-isomer of omeprazole, is the first proton pump inhibitor developed as a single isomer for the treatment of acid-related diseases.

Aim: To examine the pharmacokinetics and pharmacodynamics of esomeprazole.

Methods: In a crossover study, 12 healthy males received 5, 10 or 20 mg of esomeprazole, or 20 mg of omeprazole, once daily over 5 days. The pharmacokinetics and effects on pentagastrin-stimulated peak acid output of esomeprazole and omeprazole were studied on days 1 and 5.

Results: The area under the curve (AUC) of both esomeprazole and omeprazole increased from day 1 to day 5. The correlation between acid inhibition and AUC for esomeprazole could be well described with a sigmoid Emax model. The mean inhibition values of the pentagastrin-stimulated peak acid output on day 1 for 5, 10 and 20 mg of esomeprazole were 15%, 29% and 46%, respectively; the corresponding day 5 values were 28%, 62% and 90%. The mean inhibition values of the pentagastrin-stimulated peak acid output for omeprazole were 35% (day 1) to 79% (day 5).

Conclusions: The pharmacokinetics of esomeprazole are time and dose dependent. There was a good correlation between AUC and effect for esomeprazole. These data suggest an increased acid inhibitory effect of esomeprazole compared to omeprazole.

Publication types

  • Clinical Trial
  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Adult
  • Anti-Ulcer Agents / administration & dosage
  • Anti-Ulcer Agents / blood
  • Anti-Ulcer Agents / pharmacokinetics
  • Anti-Ulcer Agents / pharmacology*
  • Area Under Curve
  • Cross-Over Studies
  • Esomeprazole
  • Gastric Acid / metabolism*
  • Gastric Acidity Determination
  • Gastrointestinal Agents / pharmacokinetics
  • Humans
  • Male
  • Omeprazole / analogs & derivatives
  • Omeprazole / pharmacokinetics
  • Omeprazole / pharmacology*
  • Omeprazole / therapeutic use
  • Pentagastrin / pharmacokinetics
  • Proton Pump Inhibitors*
  • Proton Pumps / blood
  • Proton Pumps / pharmacokinetics
  • Stereoisomerism
  • Time Factors

Substances

  • Anti-Ulcer Agents
  • Gastrointestinal Agents
  • Proton Pump Inhibitors
  • Proton Pumps
  • Pentagastrin
  • Omeprazole
  • Esomeprazole