Korean Circ J.  2007 Nov;37(11):559-566. 10.4070/kcj.2007.37.11.559.

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

• Kim SM
• Kim DS
• Kim DI
• Kim DK
• Yang TH
• Seol SH
• Park YJ
• Lee EJ
• Choi SB
• Han YC
• Shin JG

• KMID: 1909617
• DOI: http://doi.org/10.4070/kcj.2007.37.11.559

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.

Keyword

Quinidine; Electrocardiography; Gender; Koreans

MeSH Terms

Asian Continental Ancestry Group
Electrocardiography
Female
Healthy Volunteers
Humans
Incidence
Male
Plasma
Quinidine
Tachycardia, Ventricular
Quinidine

Figure

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  Fig. 1 Representative electrocardiography before (A) and after (B) intravenous quinidine infusion, and QT interval measurement.

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  Fig. 2 Mean plasma quinidine concentration-time curve. Mean plasma quinidine concentration-time profile after intravenous infusion of quinidine (4 mg/kg) for 20 minutes in the 12 male and 12 female healthy Korean subjects. After reaching a peak at the end of the infusion, the curve declined rapidly within 15 min, followed by a slow decline. Although mean concentrations of quinidine in the men tended to be higher than those in the women, this difference was not statistically significant (p=0.127).

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  Fig. 3 Mean QTc interval-time curve with quinidine or placebo. The QTc interval was markedly prolonged in both groups after intravenous quinidine infusion compared with the QTc interval caused by saline infusion. QTc: corrected QT interval.

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  Fig. 4 Mean QTc and ΔQTc interval-time curve according to different plasma quinidine concentrations. The changes in the QTc and ΔQTc profiles were generally paralleled by plasma quinidine concentrations. QTc: corrected QT interval, ΔQTc: delta changes of corrected QT interval.

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  Fig. 5 Mean QTc and ΔQTc interval-time curve with quinidine. There were no significant differences in terms of the time courses of the quinidine-induced QTc and ΔQTc interval changes between the men and women (p=0.092 and p=0.305, respectively). QTc: corrected QT interval, ΔQTc: delta changes of corrected QT interval.

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