TY - JOUR
T1 - Interaction trial between artemether-lumefantrine (Riamet®) and quinine in healthy subjects
AU - Lefèvre, Gilbert
AU - Carpenter, Polly
AU - Souppart, Claire
AU - Schmidli, Heinz
AU - Martin, John M.
AU - Lane, Andrew
AU - Ward, Chris
AU - Amakye, Dereck
PY - 2002/10
Y1 - 2002/10
N2 - Forty-two healthy Caucasian subjects were randomized in a double-blind, parallel three-group study (14 subjects per group) to investigate potential electrocardiographic and pharmacokinetic interactions between the antimalarials artemether-lumefantrine (six-dose regimen of Riamet® over 3 days) and quinine (2-h intravenous infusion of 10 mg/kg body weight, not exceeding 600 mg in total, 2 h after the last dose of Riamet®). The study medications were all safe and well tolerated after all treatments. Neither the pharmacokinetics of lumefantrine nor the pharmacokinetics of quinine was influenced by the presence of the other drug. Plasma levels of artemether and dihydroartemisinin appeared to be lower following the combined treatment Riamet® + quinine, but this was not considered to be clinically relevant. Riamet® alone had no effect on QTc interval. Infusion of quinine alone caused a transient prolongation of QTc interval, which was consistent with the known cardiotoxicity of quinine, with this effect being slightly but significantly greater when quinine was infused after Riamet®. It would thus appear that the inherent risk of QTc prolongation of IV quinine was enhanced by prior administration of Riamet®. However, these occasional QTc prolongations, which were small in magnitude and not correlated with plasma concentrations of any of the compounds, were not considered to be of clinical importance. In conclusion, overlapping therapy with artemether-lumefantrine and IV quinine in the treatment of patients with complicated or multidrug-resistant Plasmodium falciparum malaria may result in a modest increased risk of QTc prolongation, but this is far outweighed by the potential therapeutic benefit.
AB - Forty-two healthy Caucasian subjects were randomized in a double-blind, parallel three-group study (14 subjects per group) to investigate potential electrocardiographic and pharmacokinetic interactions between the antimalarials artemether-lumefantrine (six-dose regimen of Riamet® over 3 days) and quinine (2-h intravenous infusion of 10 mg/kg body weight, not exceeding 600 mg in total, 2 h after the last dose of Riamet®). The study medications were all safe and well tolerated after all treatments. Neither the pharmacokinetics of lumefantrine nor the pharmacokinetics of quinine was influenced by the presence of the other drug. Plasma levels of artemether and dihydroartemisinin appeared to be lower following the combined treatment Riamet® + quinine, but this was not considered to be clinically relevant. Riamet® alone had no effect on QTc interval. Infusion of quinine alone caused a transient prolongation of QTc interval, which was consistent with the known cardiotoxicity of quinine, with this effect being slightly but significantly greater when quinine was infused after Riamet®. It would thus appear that the inherent risk of QTc prolongation of IV quinine was enhanced by prior administration of Riamet®. However, these occasional QTc prolongations, which were small in magnitude and not correlated with plasma concentrations of any of the compounds, were not considered to be of clinical importance. In conclusion, overlapping therapy with artemether-lumefantrine and IV quinine in the treatment of patients with complicated or multidrug-resistant Plasmodium falciparum malaria may result in a modest increased risk of QTc prolongation, but this is far outweighed by the potential therapeutic benefit.
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U2 - 10.1177/009127002401382632
DO - 10.1177/009127002401382632
M3 - Article
C2 - 12362930
AN - SCOPUS:0036785445
VL - 42
SP - 1147
EP - 1158
IS - 10
ER -