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Title: Effect of artesunate and mefloquine in combination on the Fridericia corrected QT intervals in Plasmodium falciparum infected adults from Thailand
Authors: 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
Mahidol University
Universiti Sains Malaysia
Organisation Mondiale de la Sante
University of Oxford
Luxembourg Institute of Health
Drugs for Neglected Diseases Initiative
Hopitaux universitaires de Geneve
Keywords: Immunology and Microbiology;Medicine
Issue Date: 1-Apr-2011
Citation: Tropical Medicine and International Health. Vol.16, No.4 (2011), 458-465
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. © 2011 Blackwell Publishing Ltd.
ISSN: 13653156
Appears in Collections:Scopus 2011-2015

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