Article date: March 1992
By: UM Birgersdotter, W Wong, J Turgeon, DM Roden, in Volume 33, Issue 3, pages 275-280
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.
DOI: 10.1111/j.1365-2125.1992.tb04035.x
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