Effet de l'artésunate et de la méfloquine en combinaison sur les intervalles QT de Fridericia corrigés chez les adultes infectés par Plasmodium falciparum en Thaïlande

Translated title of the contribution: Effect of artesunate and mefloquine in combination on the Fridericia corrected QT intervals in Plasmodium falciparum infected adults from Thailand

S. Krudsood, S. Looareesuwan, P. Wilairatama, W. Leowattana, N. Tangpukdee, K. Chalermrut, S. Ramanathan, V. Navaratnam, P. Olliaro, M. Vaillant, J. R. Kiechel, W. R.J. Taylor*

*Corresponding author for this work

    Research output: Contribution to journalArticleResearchpeer-review

    15 Citations (Scopus)

    Abstract

    Objective To ascertain whether mefloquine (MQ) produces electrocardiogram (ECG) changes that could be a risk for Torsades de Pointe (TdP), a potentially malignant, ventricular tachyarrhythmia. Methods We measured the Fridericia corrected QT (QTcF) intervals on 12 lead ECGs on days (D) 0, 3, 7 in Plasmodium falciparum infected adults, treated with oral artesunate (AS) and MQ as a new fixed dose (n=25) combination or loose tablets (n=25) over 3days. Target total doses were 12mg/kg of AS and 24-25mg/kg of MQ. MQ concentrations ([MQ]) were measured by HPLC. Results All ECG intervals were similar between drug arms and were combined for analysis. Mean QTcF values were 389 (D0), 407 (D3) and 399 (D7) ms (Ps<0.003 vs. D0); corresponding heart rates and [MQ]s were 83, 67 and 73 beats/minute (Ps≤0.0003 vs. D0) and 0, 3095 and 1721ng/ml. One male patient (loose arm) had a D3 QTcF 504ms (D0 406ms, D7 433ms). In the modelling of QTcF and JTcF from D0 to D7, significant effects were observed individually for [MQ], temperature and heart rate (HR). The MQ AUC 0-∞ was not a significant factor. Using a manual descending, model building approach to select variables, the HR was the only significant variable (P=0.001) over time in the model that best explained the changes in the QTcF and JTcF intervals. Conclusions In this small group of patients, slowing heart rates due to malaria resolution best explained the observed increases in the QTcF intervals.

    Translated title of the contributionEffect of artesunate and mefloquine in combination on the Fridericia corrected QT intervals in Plasmodium falciparum infected adults from Thailand
    Original languageFrench
    Pages (from-to)458-465
    Number of pages8
    JournalTropical Medicine and International Health
    Volume16
    Issue number4
    DOIs
    Publication statusPublished - Apr 2011

    Keywords

    • Artesunate
    • Electrocardiogram
    • Malaria
    • Mefloquine
    • QT interval
    • Torsades de Pointe

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