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Lookup NU author(s): Professor Simon ThomasORCiD
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Aims: To investigate the source of the apparent increased susceptibility of women to develop QT interval prolongation and torsade de pointes after the administration of drugs that delay cardiac repolarization. Methods: Plasma quinidine concentrations and electrocardiographic changes (QRS and QT intervals) were measured over 24 h following the administration of single oral doses of the QT prolonging drug quinidine (3 mg kg-1) and compared between 27 male and 21 female healthy volunteers. Results: There were no significant differences between males and females in plasma quinidine concentrations or in calculated pharmacokinetic variables. Maximum quinidine concentrations in males and females were 997 ± 56 and 871 ± 57 ng ml-1, respectively (mean difference (-125, 95% confidence intervals (CI) -239, 11 ng ml-1, P = NS). Quinidine lengthened actual (QTa) and corrected (QTc) QT intervals and the QRS interval to a greater extent in females than males (P < 0.001 for each), but there were no significant sex differences detected in the effects of quinidine on the heart rate corrected JT interval. Maximum prolongation of QTc interval was observed 2 h after quinidine and was significantly greater in women (33 ± 16 vs 24 ± 17 ms, mean difference 9 ± 20 ms, 95% CI 3, 15, P = 0.037). At this time mean differences (95% CI) were 1.0 min-1 (-2.5, 4.4, P = NS) for heart rate, 5.5 ms (3.5, 7.6, P = 0.05) for the QRS and 3.4 ms (-2.5, 9.3, P = NS) for the JTc intervals. Conclusions: Quinidine-induced increases in QTc were larger in females, but no sex differences in quinidine pharmacokinetics were found. The disparity in prolongation of cardiac repolarization is thus due to a pharmacodynamic difference which appears more complex than simply an increase in repolarization delay in females.
Author(s): El-Eraky H, Thomas SHL
Publication type: Article
Publication status: Published
Journal: British Journal of Clinical Pharmacology
Year: 2003
Volume: 56
Issue: 2
Pages: 198-204
ISSN (print): 0306-5251
ISSN (electronic): 1365-2125
Publisher: Wiley-Blackwell
URL: http://dx.doi.org/10.1046/j.1365-2125.2003.01865.x
DOI: 10.1046/j.1365-2125.2003.01865.x
PubMed id: 12895193
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