Artemether-lumefantrine for the treatment of multidrug-resistant falciparum malaria

Abstract

The efficacy and safety of the 6-dose regimen of artemether-lumefantrine were assessed in an open randomized trial in children and adults presenting with acute, uncomplicated Plasmodium falciparum malaria in Thailand between November 1997 and March 1998. 200 patients were enrolled in 2 centres: 150 received artemether-lumefantrine (i.e., a median total dose of 9.6 mg/kg [interquartile range 8.7-10.7] and 57.9 mg/kg of lumefantrine [52.4-64.0]) and 50 the standard combination of artesunate (12 mg/kg over 3 d) and mefloquine (25 mg/kg). All patients had rapid initial clinical and parasitological responses. The 28 d cure rates were high: 97.7% (95% confidence interval [95% CI] 93.5-99.5%) for artemether-lumefantrine and 100% (95% CI 92.5-100%) for artesunate-mefloquine. The 6-dose regimen of artemether-lumefantrine was better tolerated than, and as effective as, artesunate-mefloquine, the current standard treatment in this area of multidrug-resistant P. falciparum malaria.

Development of artemether and lumefantrine co-loaded nanostructured lipid carriers: physicochemical characterization and in vivo antimalarial activity

“…In artemether-loaded NLC-treated group, the parasitemia was $31.9 ± 13% on day 19, and all mice died before 28 d. In lumefantrine-loaded NLC-treated groups, on the 19th d, parasitemia was 22 ± 15% leading to death of five mice in a group within 28 d, and only single mice survived up to 28 d. Similar type of enhanced antimalarial activity was observed in earlier studies after encapsulating either artemether or lumefantrine in various carrier systems like NLCs, emulsions, liposome's (Joshi et al, 2008;Santos-Magalhães & Mosqueira, 2010;Sosnik & Amiji, 2010). In contrary, mice treated with the artemether and lumefantrine combination either in NLCs or simple oil suspension, treated animals have shown significant decrease in parasitemia on day 19, and !50% mice survived beyond 28 d. The increased antiparasitic activity may be due to the presence of two drugs, which have shown similar increased therapeutic efficiency when used in combination in earlier clinical trials (van Vugt et al, 2000). In addition, between these two groups, artemether and lumefantrine co-loaded NLC-treated group has shown !90% decrease in parasitemia (4 ± 3%) in comparison to artemether and lumefantrine oil suspension-treated animals, which have shown the parasitemia of $13 ± 4% on day 19 due to the availability of artemether for prolonged period, which helps to reduce the parasitemia followed by availability of the lumefantrine, which will clear the remaining parasites and artemether resistant parasites if any.…”

Chlorproguanil–Dapsone–Artesunate versus Chlorproguanil–Dapsone: A Randomized, Double-Blind, Phase III Trial in African Children, Adolescents, and Adults with Uncomplicated Plasmodium falciparum Malaria

“…In a pivotal study of 1,850 children, CPG-DDS had Day 14 cure rates of 93-99% and was more effective than sulfadoxinepyrimethamine (SP) in three of five African countries. 4 Artemisinin derivatives are active against multidrug-resistant P. falciparum , 5,6 rapidly reduce asexual parasitemia, 7,8 and are gametocytocidal, potentially reducing transmission. [9][10][11][12][13] However, the short half-life of these agents precludes their use as monotherapy for uncomplicated malaria.…”

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

“…9,12,[15][16][17][18][19] The 6-dose regimen of AL was better tolerated than, and as effective as, artesunate-mefloquine against multi-drugresistant falciparum malaria. 8,20 Furthermore, AL was better tolerated than the comparator drugs used in some trials. Higher incidences of vomiting and pruritus were reported with chloroquine.…”

“…Lumefantrine (benflumetol) is an aryl amino alcohol which belongs to the same chemical class as quinine, mefloquine and halofantrine. [7][8][9][10] Lumefantrine is a class II blood schizontocide, which inhibits heme polymerization. 10,11 The combination of artemether, that rapidly reduces parasite biomass, with longer-acting lumefantrine, that eliminates residual parasites, has proven to be highly effective in achieving parasitologic cure, symptom relief, and reduction of gametocyte carriage.…”

“…Dizziness, nausea and vomiting were more common with mefloquine while dizziness, abdominal pain, nausea and vomiting were more frequent with quinine. 8 Considering the acclaimed efficacy and widespread use of AL, the knowledge of its sub-acute and delayed toxicity patterns will be essential in comparative risk assessment and management of malaria patients. Hence this study set out to evaluate the toxicity profile of normal and high doses of AL in rats.…”