A randomized, double-blind, parallel-group, comparative safety, and efficacy trial of oral co-artemether versus oral chloroquine in the treatment of acute uncomplicated Plasmodium falciparum malaria in adults in India.

Abstract

Abstract. In India, treatment of acute, uncomplicated Plasmodium falciparum malaria is becoming increasingly difficult due to resistance to chloroquine, thus there is a need for new antimalarial drugs. CGP 56697 (co-artemether), a new drug, is a combination of artemether and lumefantrine in a single oral formulation (one tablet ϭ 20 mg of artemether plus 120 mg of lumefantrine). In a double-blind study, 179 patients with acute uncomplicated P. falciparum malaria were randomly assigned to receive either CGP (n ϭ 89) given as a short course of 4 ϫ 4 tablets over a 48-hr period or chloroquine (n ϭ 90) given as four tablets (one tablet ϭ 150 mg of chloroquine base) initially, followed by two tablets each at 6-8, 24, and 48 hr. Due to a death in the chloroquine group and a decrease in the chloroquine cure rate to Ͻ 50% (based on the blinded overall cure rate at that time), recruitment was terminated prematurely. CGP 56697 showed a superior 28-day cure rate (95.4% versus 19.7%; P Ͻ 0.001), time to parasite clearance (median ϭ 36 versus 60 hr; P Ͻ 0.001), and resolution of fever (median ϭ 18 versus 27 hr; P ϭ 0.0456). This drug provides a safe, effective, and rapid therapy for the treatment of acute uncomplicated P. falciparum malaria.

Randomized, Double-Blind, Placebo-Controlled Clinical Trial of a Two-Day Regimen of Dihydroartemisinin-Piperaquine for Malaria Prevention Halted for Concern over Prolonged Corrected QT Interval

“…This would have required additional ECG studies at 90 min postdose to coincide with the C max of dihydroartemisinin (32). Several studies with artemisinin-containing oral compounds have demonstrated excellent cardiac safety profiles despite higher peak plasma concentrations compared to intramuscular formulations (17,(33)(34)(35). We cannot determine whether our findings would be similar for the conventional 3-day regimen of dihydroartemisinin-piperaquine.…”

Pharmacokinetics and electrocardiographic pharmacodynamics of artemether‐lumefantrine (Riamet®) with concomitant administration of ketoconazole in healthy subjects

“…Although co-artemether, in contrast to other antimalarials like quinine or halofantrine, has never been reported to cause any relevant cardiotoxicity when given alone [28][29][30][31] or in combination with mefloquine [32] or quinine [16], electrocardiographic parameters were closely monitored during this study.…”

Assessment of the Sub-Acute and Delayed Toxicity of Artemether-Lumefantrine Combination in Rats

“…These changes were considerably less than asymptomatic and no adverse clinical cardiac events were reported. 16,[47][48][49][50] In conclusion, the once daily oral administration of increasing doses of AL to rats for one week, elicited varying sub-acute and delayed hematological, biochemical and histopathological effects. The AL elicited hyperglycemic effect, as well as stimulatory effects on haemopoeisis and immune response, but no significant sub-acute and delayed toxic effects on the liver, kidneys and heart.…”