Possible Interaction: Quinidine and Encainide

“Because quinidine has been reported recently to be a potent inhibitor of the enzyme responsible for this polymorphism (cytochrome P450db1), we tested the hypothesis that quinidine would selectively inhibit encainide metabolism and alter its effects in subjects with the extensive metabolism phenotype for debrisoquine oxidation.”

“In contrast, in poor metabolizers, quinidine did not change encainide disposition kinetics and neither encainide alone nor encainide plus quinidine significantly altered electrocardiographic intervals.(ABSTRACT TRUNCATED AT 250 WORDS)”

“In extensive metabolizers, quinidine decreased encainide systemic clearance from 935 +/- 541 to 190 +/- 77 ml/min and encainide nonrenal clearance from 782 +/- 474 to 95 +/- 32 ml/min (both P less than .02).”

“In this population, quinidine significantly increased encainide elimination half-life from 1.8 +/- 1.2 to 7.7 +/- 2.4 hr and fractional urinary recovery of unchanged encainide from 17.5 +/- 7.6 to 47.4 +/- 7.8% (both P less than .001).”

“Moreover, poor metabolism and QRS prolongation during encainide were blunted by addition of quinidine ; the extent of quinidine-induced reversal of encainide-related ECG changes was also correlated with debrisoquine ratio (r = 0.91).”

“Therefore, the purpose of this study was to test the hypothesis that quinidine would inhibit sodium channel block (and by inference arrhythmia suppression) during encainide therapy in patients with the extensive metabolizer phenotype.”