Quinidine administration resulted in a 44% greater QTc interval prolongation relative to serum concentration in women compared to men (42.2 vs 29.3 ms/microg per mL, P<0.001).
RCT (n=24)
Single-blind
crossover
Does a single intravenous dose of quinidine cause greater QTc interval prolongation in healthy young women compared to men?
Quinidine causes significantly greater QTc prolongation in women than in men at equivalent serum concentrations, which may explain the higher risk of drug-induced torsades de pointes in women.
Effect estimate: 44% greater
Absolute Event Rate: 42.2% vs 29.3%
p-value: p=<.001
BACKGROUND: Prolongation of the electrocardiographic QT interval by drugs is associated with the occurrence of a potentially lethal form of polymorphic ventricular tachycardia termed torsades de pointes. Women are at greater risk than men for development of this adverse event when taking drugs that prolong the QT interval. 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 healthy young men and women. METHODS: Twelve women and 12 men received a single intravenous dose of quinidine (4 mg/kg) or placebo in a single-blind, randomized crossover trial. Total plasma and protein-free concentrations of quinidine and 3-hydroxyquinidine were measured in serum. QT intervals were determined and corrected for differences in heart rate with use of the method of Bazett (QTc = QT/RR1/2). RESULTS: As expected, the mean QTc interval at baseline was longer for women than for men (mean +/- SD; 407 +/- 7 versus 395 +/- 9 ms, P < .05). The slope of the relationship between change in the QTc interval (delta QTc) from baseline to the serum concentration of quinidine was 44% greater for women than for men (mean +/- SE; 42.2 +/- 3.4 versus 29.3 +/- 2.6 ms/microg per mL, P < .001). These results were not influenced by analysis of 3-hydroxyquinidine, free concentrations of quinidine and 3-hydroxyquinidine, or the JT interval. CONCLUSIONS: Quinidine causes greater QT prolongation in women than in men at equivalent serum concentrations. This difference may contribute to the greater incidence of drug-induced torsades de pointes observed in women taking quinidine and has implications for other cardiac and noncardiac drugs that prolong the QTc interval. Adjustment of dosages based on body size alone are unlikely to substantially reduce the increased risk of torsades de pointes in women.
R.E. Benton (Sat,) conducted a rct in Healthy (n=24). quinidine vs. placebo was evaluated on slope of the relationship between change in the QTc interval from baseline to the serum concentration of quinidine (44% greater, p=<.001). Quinidine administration resulted in a 44% greater QTc interval prolongation relative to serum concentration in women compared to men (42.2 vs 29.3 ms/microg per mL, P<0.001).