Stereoselective genetically-determined interaction between chronic flecainide and quinidine in patients with arrhythmias

Br J Clin Pharmacol. 1992 Mar;33(3):275-80. doi: 10.1111/j.1365-2125.1992.tb04035.x.


1. Recent reports have indicated a role for the P450IID6 polymorphism in the stereoselective disposition of single doses of the antiarrhythmic flecainide. 2. In this study, we evaluated the effects of adding low dose quinidine, a potent inhibitor of P450IID6, to chronic flecainide therapy in patients with arrhythmias. 3. In five extensive metabolizer patients, quinidine significantly reduced the clearance of R-(-)-flecainide, from 395 +/- 121 (s.d.) to 335 +/- 88 ml min-1. This change was attributable to a decrease in metabolic clearance, was accompanied by decreased formation of the two major metabolites of flecainide and was not observed in a poor metabolizer subject. The renal clearance of R-(-)-flecainide rose significantly. 4. Quinidine did not alter the clearance of S-(+)-flecainide. 5. The pharmacologic effects of flecainide therapy (QRS widening, % arrhythmia suppression) were slightly, but not significantly, increased. 6. In extensive metabolizer patients receiving chronic flecainide, increased plasma concentrations will develop if P450IID6 is inhibited.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Arrhythmias, Cardiac / drug therapy*
  • Cytochrome P-450 CYP2D6
  • Cytochrome P-450 Enzyme System / genetics
  • Drug Interactions
  • Flecainide / pharmacokinetics
  • Flecainide / pharmacology
  • Flecainide / therapeutic use*
  • Humans
  • Mixed Function Oxygenases / genetics
  • Polymorphism, Genetic
  • Quinidine / pharmacokinetics
  • Quinidine / pharmacology
  • Quinidine / therapeutic use*


  • Cytochrome P-450 Enzyme System
  • Mixed Function Oxygenases
  • Cytochrome P-450 CYP2D6
  • Quinidine
  • Flecainide