Pantoprazole has no influence on steady state pharmacokinetics and pharmacodynamics of metoprolol in healthy volunteers

Int J Clin Pharmacol Ther. 1996 Oct;34(10):420-3.


The new H+/K+ ATPase inhibitor pantoprazole, a substituted benzimidazole, is metabolized by the hepatic cytochrome P450 enzymes 2C19 or 3A4 and subsequently undergoes phase II metabolism. The widely used beta 1-adrenoreceptor-blocking agent metoprolol is metabolized via CYP2D6. The influence of pantoprazole on the pharmacokinetics of an orally administered zero order kinetics formulation (ZOK) of metoprolol was the objective of this study. Eighteen volunteers (9 female, 9 male, age 20-44 years) completed the randomized, double-blind crossover study. Each subject received either 95 mg metoprolol and placebo (reference (R)) or 95 mg metoprolol and 40 mg pantoprazole (test (T)) as oral doses (sid) for 5 consecutive days. On day 5 of each period serum concentrations of R- and S-metoprolol were determined and a treadmill ergometry was performed. The primary pharmacokinetic characteristics for extent and rate of absorption were AUC(0-24h) and % PTF, respectively. To assess the pharmacodynamic effect of metoprolol the excess area under the effect vs. time curve was calculated for heart rate during ergometry (AUCexHR). Point estimate and 90% confidence limits (CI) for the ratios of population medians of T and R were given. The respective point estimates (90% CI) of the ratios of both primary and secondary characteristics were entirely within the equivalence range of 0.80 and 1.25 for both enantiomers of metoprolol. Moreover, equivalence could be shown for the pharmacodynamic characteristic AUCexHR. Hence, it was concluded that pantoprazole does not interact with metoprolol pharmacokinetics or pharmacodynamics. Therefore, no dose adjustment of metoprolol during therapy with pantoprazole is necessary.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial

MeSH terms

  • 2-Pyridinylmethylsulfinylbenzimidazoles
  • Administration, Oral
  • Adrenergic beta-Antagonists / administration & dosage
  • Adrenergic beta-Antagonists / pharmacokinetics*
  • Adrenergic beta-Antagonists / pharmacology
  • Adult
  • Anti-Ulcer Agents / administration & dosage
  • Anti-Ulcer Agents / pharmacology*
  • Benzimidazoles / administration & dosage
  • Benzimidazoles / pharmacology*
  • Blood Chemical Analysis
  • Cross-Over Studies
  • Double-Blind Method
  • Drug Interactions
  • Exercise Test
  • Female
  • Heart Rate / drug effects
  • Humans
  • Male
  • Metoprolol / administration & dosage
  • Metoprolol / blood
  • Metoprolol / pharmacokinetics*
  • Metoprolol / pharmacology
  • Omeprazole / analogs & derivatives
  • Pantoprazole
  • Proton Pump Inhibitors*
  • Stereoisomerism
  • Sulfoxides / administration & dosage
  • Sulfoxides / pharmacology*


  • 2-Pyridinylmethylsulfinylbenzimidazoles
  • Adrenergic beta-Antagonists
  • Anti-Ulcer Agents
  • Benzimidazoles
  • Proton Pump Inhibitors
  • Sulfoxides
  • Pantoprazole
  • Metoprolol
  • Omeprazole