caa a22 4500 475818970 CHVBK 20180406123817.0 cr unu---uuuuu 170329e20000801xx s 000 0 eng 10.1007/s002280000155 doi (NATIONALLICENCE)springer-10.1007/s002280000155 Cardiac effects of co-artemether (artemether/lumefantrine) and mefloquine given alone or in combination to healthy volunteers [Elektronische Daten] [M. Bindschedler, G. Lefèvre, F. Ezzet, N. Schaeffer, I. Meyer, M. S. Thomsen] Co-artemether is an oral tablet of artemether (20 mg) and lumefantrine (120 mg) for the treatment of falciparum malaria. Administration in the presence of mefloquine is likely, as co-artemether may be used following failure of antimalarial prophylaxis or treatment with mefloquine. Objective: The effects on the QTc interval were compared among treatment with three doses of mefloquine (500, 250, 250 mg over 12 h) followed by six doses of co-artemether (6 × 4 tablets over 60 h) and either treatment alone. The study was performed in a randomised, double-blind, parallel group design in 14 healthy male subjects per dose group. Methods: Electrocardiograms (ECGs) were recorded before dosing and repeatedly thereafter. The Bazett formula was used to calculate the QTc interval. The maximum and average QTc intervals for the first, third and sixth dosing intervals of co-artemether treatment were compared among treatments. Drug plasma concentrations were determined at identical times with the ECG recordings for exploratory pharmacokinetic/pharmacodynamic evaluation. Results: No clinically relevant differences in the QTc interval were observed after sequential administration of mefloquine and co-artemether relative to either treatment given alone, and there were no clinically relevant study drug-related effects on the QTc interval after either treatment. Plasma drug measurements revealed adequate systemic exposure to artemether, dihydroartemisinin, lumefantrine and mefloquine, well in line with the clinical setting. No correlation between the length of the QTc interval and plasma drug concentrations was found for any of the compounds. Conclusions: Untoward effects on the QTc interval are unlikely to occur when co-artemether is administered following prophylaxis or treatment with mefloquine. Springer-Verlag Berlin Heidelberg, 2000 Key words Healthy volunteers nationallicence QTc nationallicence Benflumetol nationallicence Bindschedler M. Novartis Pharma Ltd, Research and Development Department, CH-4002 Basel, Switzerland, CH aut Lefèvre G. Novartis Pharma Ltd, Research and Development Department, CH-4002 Basel, Switzerland, CH aut Ezzet F. Novartis Pharma Ltd, Research and Development Department, CH-4002 Basel, Switzerland, CH aut Schaeffer N. Novartis Pharma Ltd, Research and Development Department, CH-4002 Basel, Switzerland, CH aut Meyer I. Quintiles (Innovex) GmbH, Freiburg, Germany, DE aut Thomsen M. S. Novartis Pharma Ltd, Research and Development Department, CH-4002 Basel, Switzerland, CH aut https://doi.org/10.1007/s002280000155 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s002280000155 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Bindschedler M. Novartis Pharma Ltd, Research and Development Department, CH-4002 Basel, Switzerland, CH aut NATIONALLICENCE 700 1- Lefèvre G. Novartis Pharma Ltd, Research and Development Department, CH-4002 Basel, Switzerland, CH aut NATIONALLICENCE 700 1- Ezzet F. Novartis Pharma Ltd, Research and Development Department, CH-4002 Basel, Switzerland, CH aut NATIONALLICENCE 700 1- Schaeffer N. Novartis Pharma Ltd, Research and Development Department, CH-4002 Basel, Switzerland, CH aut NATIONALLICENCE 700 1- Meyer I. Quintiles (Innovex) GmbH, Freiburg, Germany, DE aut NATIONALLICENCE 700 1- Thomsen M. S. Novartis Pharma Ltd, Research and Development Department, CH-4002 Basel, Switzerland, CH aut Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer