Effect of fluvoxamine on the pharmacokinetics of quinidine

Eur J Clin Pharmacol. 1999 Aug;55(6):451-6. doi: 10.1007/s002280050655.


Objective: To investigate the possible involvement of cytochromes CYP1A2 and CYP2C19 in the in vivo oxidative metabolism of quinidine.

Methods: This was an open study of six healthy young male volunteers. The pharmacokinetics of a 200-mg single oral dose of quinidine were studied before and during daily treatment with 100 mg fluvoxamine. Biomarkers of other isozyme activities in the form of caffeine, sparteine, mephenytoin, tolbutamide and cortisol metabolism were applied.

Results: The results showed a statistically significant median reduction of 2944% in the quinidine total apparent oral clearance, partial clearances by 3-hydroxylation and N-oxidation and residual clearance during fluvoxamine treatment. Renal clearance was unaffected by fluvoxamine.

Conclusions: The effect of fluvoxamine on the formation clearances of 3-hydroxyquinidine and quinidine-N-oxide most likely reflects inhibition of cytochrome P4503A4 by fluvoxamine at clinically relevant doses. The results of this study do not rule out a possible involvement of CYP1A2 and CYP2C19 in the in vivo oxidative metabolism of quinidine.

Publication types

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

MeSH terms

  • Anti-Arrhythmia Agents / metabolism
  • Anti-Arrhythmia Agents / pharmacokinetics*
  • Aryl Hydrocarbon Hydroxylases*
  • Cytochrome P-450 CYP1A2 / metabolism
  • Cytochrome P-450 CYP1A2 Inhibitors
  • Cytochrome P-450 Enzyme Inhibitors
  • Cytochrome P-450 Enzyme System / metabolism
  • Drug Interactions
  • Enzyme Inhibitors / adverse effects
  • Enzyme Inhibitors / pharmacology
  • Fluvoxamine / adverse effects
  • Fluvoxamine / pharmacology*
  • Humans
  • Male
  • Metabolic Clearance Rate
  • Quinidine / analogs & derivatives
  • Quinidine / metabolism
  • Quinidine / pharmacokinetics*
  • Quinidine / pharmacology
  • Steroid 16-alpha-Hydroxylase*
  • Steroid Hydroxylases / antagonists & inhibitors
  • Steroid Hydroxylases / metabolism


  • Anti-Arrhythmia Agents
  • Cytochrome P-450 CYP1A2 Inhibitors
  • Cytochrome P-450 Enzyme Inhibitors
  • Enzyme Inhibitors
  • 3-hydroxyquinidine
  • Cytochrome P-450 Enzyme System
  • Steroid Hydroxylases
  • Aryl Hydrocarbon Hydroxylases
  • CYP1A2 protein, human
  • Cytochrome P-450 CYP1A2
  • Steroid 16-alpha-Hydroxylase
  • Quinidine
  • Fluvoxamine