Quinidine-Induced QTc Interval Prolongation and Gender Differences in Healthy Korean Subjects

ABSTRACT

BACKGROUND AND OBJECTIVES: Drug-induced electrocardiographic QT interval prolongation is associated with the occurrence of a potentially lethal form of polymorphic ventricular tachycardia, termed 'torsades de pointes' (TdP). Women are at greater risk for the development of drug-induced TdP. To determine whether this may be the result of gender-specific differences in the effect of quinidine on cardiac repolarization, we compared the degree of quinidine-induced QT interval lengthening in young, healthy volunteers. SUBJECTS AND METHODS: Twelve women and 12 men each received a single intravenous dose of quinidine (4 mg/kg) or placebo in a single-blinded, randomized crossover trial. Total plasma concentrations of quinidine were measured, and QT and corrected QT intervals were analyzed. RESULTS: As expected, the mean QTc interval at baseline was longer for women than for men (443.6+/-26.9 vs 402.1+/-31.3 msec, respectively, p=0.037). The mean value of the maximal DeltaQTc after quinidine infusion was higher in women (134.4+/-46.4 vs 117.5+/-37.7 msec, respectively, p=0.029), and the mean value of the minimal DeltaQTc for 1 hour after quinidine infusion was also higher in the female group (47.6+/-15.7 vs 83.7+/-25.4 msec, p=0.034). However, there were no significant differences in the time courses of the changes in the quinidine-induced QTc and DeltaQTc interval between the two groups (p=0.092, and p=0.305, respectively). CONCLUSION: Quinidine causes greater QT prolongation in women at equivalent serum concentrations. This difference may contribute to the greater incidence of drug-induced TdP observed in women taking quinidine, and has implications for other cardiac and noncardiac drugs that prolong the QTc interval.