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Investigation of potential mechanisms of sex differences in quinidine-induced torsade de pointes risk.

AbstractINTRODUCTION:
The electrocardiographic index Tpeak-Tend has been proposed as a marker of dispersion of repolarization and may be a stronger predictor of torsade de pointes risk than QTc prolongation.
METHODS AND RESULTS:
We assessed whether quinidine-induced Tpeak-Tend prolongation is greater in women than men. The relationship between QTc prolongation and quinidine concentration was greater in women than men (38 ± 10 vs. 28 ± 9 ms/μg/ml, p=0.02), but there was no difference for Tpeak-Tend prolongation (39 ± 13 vs. 32 ± 13 ms/μg/ml, p=0.21). There was a delay (hysteresis) between peak concentration and both maximum QTc and Tpeak-Tend prolongation and a trend toward higher serum quinidine concentration in men than women. Analysis controlling for hysteresis showed no sex difference for QTc (55 ± 18 vs. 43 ± 19 ms/μg/ml, p=0.14), without changing the lack of sex difference with Tpeak-Tend (61 ± 22 vs. 55 ± 21 ms/μg/ml, p=0.49).
CONCLUSIONS:
Women do not have a greater quinidine-induced Tpeak-Tend prolongation than men. Sex differences in hysteresis and serum quinidine concentration in this study may have contributed to sex differences in quinidine-induced QTc prolongation.
AuthorsJose Vicente, Jacob Simlund, Lars Johannesen, Frida Sundh, Jeffry Florian, Martin Ugander, Galen S Wagner, Raymond L Woosley, David G Strauss
JournalJournal of electrocardiology (J Electrocardiol) 2015 Jul-Aug Vol. 48 Issue 4 Pg. 533-8 ISSN: 1532-8430 [Electronic] United States
PMID25796102 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)
CopyrightPublished by Elsevier Inc.
Chemical References
  • Anti-Arrhythmia Agents
  • Quinidine
Topics
  • Adolescent
  • Adult
  • Anti-Arrhythmia Agents (administration & dosage, adverse effects, pharmacokinetics)
  • Dose-Response Relationship, Drug
  • Electrocardiography (drug effects)
  • Feasibility Studies
  • Female
  • Humans
  • Male
  • Quinidine (administration & dosage, adverse effects, blood)
  • Reproducibility of Results
  • Risk Assessment (methods)
  • Sensitivity and Specificity
  • Sex Factors
  • Single-Blind Method
  • Torsades de Pointes (blood, chemically induced, diagnosis)
  • Young Adult

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