Olliaro, P., Kiechel, J.R., Navaratnam, V., Ramanathan, S., Vaillant, M., Krudsood, S., Looareesuwan, S., Tangpukdee, N., Wilairatama, P., Leowattana, W., Chalermrut, K., Taylor, V.R.J.
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 combination (n = 25) or loose tablets (n = 25) over 3 days. Target total doses were 12 mg/kg of AS and 24–25 mg/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-∞ 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.
Tropical Medicine & International Health (2011), published online before print, 10 Jan 2011 [DOI: 10.1111/j.1365-3156.2010.02714.x].