Effects of fluvoxamine on lansoprazole pharmacokinetics in relation to CYP2C19 genotypes

J Clin Pharmacol. 2004 Nov;44(11):1223-9. doi: 10.1177/0091270004269015.


Lansoprazole is a substrate of CYP2C19 and CYP3A4. The aim of this study was to compare the inhibitory effects of fluvoxamine, an inhibitor of CYP2C19, on the metabolism of lansoprazole between CYP2C19 genotypes. Eighteen volunteers--of whom 6 were homozygous extensive metabolizers (EMs), 6 were heterozygous EMs, and 6 were poor metabolizers (PMs) for CYP2C19--received three 6-day courses of either daily 50 mg fluvoxamine or placebo in a randomized fashion with a single oral 60-mg dose of lansoprazole on day 6 in all cases. Plasma concentrations of lansoprazole and its metabolites, 5-hydroxylansoprazole and lansoprazole sulfone, were monitored up to 24 hours after the dosing. During placebo administration, there was a significant difference in the area under the plasma concentration-time curve from time 0 to infinity (AUC(0-infinity)) of lansoprazole between CYP2C19 genotypes. Fluvoxamine treatment increased AUC(0-infinity) of lansoprazole by 3.8-fold (P < .01) in homozygous EMs and by 2.5-fold (P < .05) in heterozygous EMs, whereas no difference in any pharmacokinetic parameters was found in PMs. There was a significant difference in the fluvoxamine-mediated percentage increase in the AUC(0-infinity) of lansoprazole between CYP2C19 genotypes. The present study indicates that there are significant drug interactions between lansoprazole and fluvoxamine in EMs. CYP2C19 is predominantly involved in lansoprazole metabolism in EMs.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial

MeSH terms

  • 2-Pyridinylmethylsulfinylbenzimidazoles
  • Adult
  • Anti-Ulcer Agents / metabolism
  • Anti-Ulcer Agents / pharmacokinetics*
  • Area Under Curve
  • Aryl Hydrocarbon Hydroxylases / antagonists & inhibitors
  • Aryl Hydrocarbon Hydroxylases / genetics*
  • Aryl Hydrocarbon Hydroxylases / metabolism
  • Cross-Over Studies
  • Cytochrome P-450 CYP2C19
  • Double-Blind Method
  • Drug Synergism
  • Female
  • Fluvoxamine / pharmacology*
  • Genotype
  • Humans
  • Lansoprazole
  • Male
  • Mixed Function Oxygenases / antagonists & inhibitors
  • Mixed Function Oxygenases / genetics*
  • Mixed Function Oxygenases / metabolism
  • Omeprazole / analogs & derivatives*
  • Omeprazole / metabolism
  • Omeprazole / pharmacokinetics*
  • Proton Pump Inhibitors
  • Serotonin Uptake Inhibitors / pharmacology*


  • 2-Pyridinylmethylsulfinylbenzimidazoles
  • Anti-Ulcer Agents
  • Proton Pump Inhibitors
  • Serotonin Uptake Inhibitors
  • Lansoprazole
  • Lansoprazole Sulfone
  • Mixed Function Oxygenases
  • Aryl Hydrocarbon Hydroxylases
  • CYP2C19 protein, human
  • Cytochrome P-450 CYP2C19
  • Omeprazole
  • Fluvoxamine