STEREOSELECTIVE GENETICALLY-DETERMINED INTERACTION BETWEEN CHRONIC FLECAINIDE AND QUINIDINE IN PATIENTS WITH ARRHYTHMIAS

1 Recent reports have indicated a role for the P450IID6 polymorphism in the stereo-selective 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.