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 correctedQT (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 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. MeanQTcF 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 1721 ng/ml. One male patient (loose arm) had a D3 QTcF 504 ms (D0 406 ms, D7 433 ms). 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.
RCT Entities:
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 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 < 0.003 vs. D0); corresponding heart rates and [MQ]s were 83, 67 and 73 beats/minute (Ps ≤ 0.0003 vs. D0) and 0, 3095 and 1721 ng/ml. One male patient (loose arm) had a D3 QTcF 504 ms (D0 406 ms, D7 433 ms). 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.
Authors: Bernhards Ogutu; Elizabeth Juma; Charles Obonyo; Vincent Jullien; Gwenaelle Carn; Michel Vaillant; Walter Robert John Taylor; Jean-René Kiechel Journal: Malar J Date: 2014-12-16 Impact factor: 2.979
Authors: Thanaporn Wattanakul; Bernhards Ogutu; Abdunoor M Kabanywanyi; Kwaku-Poku Asante; Abraham Oduro; Alex Adjei; Ali Sie; Esperanca Sevene; Eusebio Macete; Guillaume Compaore; Innocent Valea; Isaac Osei; Markus Winterberg; Margaret Gyapong; Martin Adjuik; Salim Abdulla; Seth Owusu-Agyei; Nicholas J White; Nicholas P J Day; Halidou Tinto; Rita Baiden; Fred Binka; Joel Tarning Journal: Antimicrob Agents Chemother Date: 2020-06-23 Impact factor: 5.191
Authors: Borimas Hanboonkunupakarn; Rob W van der Pluijm; Richard Hoglund; Sasithon Pukrittayakamee; Markus Winterberg; Mavuto Mukaka; Naomi Waithira; Kesinee Chotivanich; Pratap Singhasivanon; Nicholas J White; Arjen M Dondorp; Joel Tarning; Podjanee Jittamala Journal: Antimicrob Agents Chemother Date: 2019-07-25 Impact factor: 5.191
Authors: George O Adjei; Collins Oduro-Boatey; Onike P Rodrigues; Lotte C Hoegberg; Michael Alifrangis; Jorgen A Kurtzhals; Bamenla Q Goka Journal: Malar J Date: 2012-12-17 Impact factor: 2.979