Metabolic disposition of pantoprazole, a proton pump inhibitor, in relation to S-mephenytoin 4'-hydroxylation phenotype and genotype

Clin Pharmacol Ther. 1997 Dec;62(6):619-28. doi: 10.1016/S0009-9236(97)90081-3.


Objectives: To assess the possible relationship between the metabolic disposition of pantoprazole and genetically determined S-mephenytoin 4'-hydroxylation phenotype and genotype.

Methods: The pharmacokinetic disposition of pantoprazole was investigated in 14 Japanese male volunteers (seven extensive and seven poor metabolizers of S-mephenytoin). All subjects received a single 40 mg oral dose of pantoprazole as the enteric-coated formulation.

Results: An interphenotypic difference in the metabolic disposition of pantoprazole was observed: the mean values for area under the concentration-time curve (AUC), elimination half-life (t1/2), and apparent oral clearance were significantly (p < 0.01) greater, longer, and lower, respectively, in the poor metabolizers than in the extensive metabolizers. The mean AUC of pantoprazole sulfone was greater (p < 0.01) in the poor metabolizers than in the extensive metabolizers, whereas the mean AUC of the main demethylated metabolite (M2) was lower (p < 0.01) in the poor metabolizers than in the extensive metabolizers. A significant negative correlation was observed between the individual values for log10% urinary excretion of 4'-hydroxymephenytoin and AUC of pantoprazole (rs = -0.816; p < 0.005). The CYP2C19 genotyping test results were found to be in a complete accordance with the phenotypes.

Conclusion: These data indicated that the metabolic disposition of pantoprazole is under the pharmacogenetic control of S-mephenytoin 4'-hydroxylase (CYP2C19).

Publication types

  • Comparative Study

MeSH terms

  • 2-Pyridinylmethylsulfinylbenzimidazoles
  • Adult
  • Anti-Ulcer Agents / pharmacokinetics*
  • Anti-Ulcer Agents / pharmacology
  • Area Under Curve
  • Aryl Hydrocarbon Hydroxylases*
  • Benzimidazoles / pharmacokinetics*
  • Benzimidazoles / pharmacology
  • Cytochrome P-450 CYP2C19
  • Cytochrome P-450 Enzyme System / genetics
  • Cytochrome P-450 Enzyme System / metabolism*
  • Enzyme Inhibitors / pharmacokinetics*
  • Enzyme Inhibitors / pharmacology
  • Half-Life
  • Humans
  • Japan
  • Male
  • Mephenytoin / analogs & derivatives
  • Mephenytoin / urine
  • Metabolic Clearance Rate
  • Mixed Function Oxygenases / genetics
  • Mixed Function Oxygenases / metabolism*
  • Omeprazole / analogs & derivatives
  • Pantoprazole
  • Proton Pump Inhibitors*
  • Sulfoxides / pharmacokinetics*
  • Sulfoxides / pharmacology


  • 2-Pyridinylmethylsulfinylbenzimidazoles
  • Anti-Ulcer Agents
  • Benzimidazoles
  • Enzyme Inhibitors
  • Proton Pump Inhibitors
  • Sulfoxides
  • 4-hydroxymephenytoin
  • Cytochrome P-450 Enzyme System
  • Pantoprazole
  • Mixed Function Oxygenases
  • Aryl Hydrocarbon Hydroxylases
  • CYP2C19 protein, human
  • Cytochrome P-450 CYP2C19
  • Omeprazole
  • Mephenytoin