Lumefantrine

Lumefantrine is an antimalarial drug. It is only used in combination with artemether. This is combination is frequently the first-line medication for Plasmodium falciparum malaria. Lumefantrine has a much longer half-life compared to artemether, and is therefore thought to clear any residual parasites that remain after combination treatment.

Mechanism of action

Exact mechanism by which lumefantrine acts on erythrocytic stages of Plasmodium falciparum is unknown. However, it was shown to exert its action through possible two mechanisms:

inhibiting β-hematin formation by creating complexes with hemin
inhibiting nucleic acid and protein synthesis

Moreover, it was shown to interact with human sodium/potassium ATPase subunit α1.

Metabolism

Lumefantrine is metabolised in the liver by cytochrome P450 3A4 isoenzyme and 2D6, yielding desbutyl-lumefantrine as a major metabolite.

Adverse effects

Lumefantrine, as used in combination with artemether, was shown to induce the following side effects:

prolongation of QT interval, especially in combination with other drugs exhibiting the same effects or in patients with congenital prolongation of the QT interval
hypersensitivity reactions
interactions with CYP3A4 and CYP2D6 inducing or inhibiting drugs
infertility

People taking efavirenz as a part of HIV therapy should be wary of potential deviations during treatment, due to a decrease of AUC of this antiretroviral.

History

Lumefantrine, along with pyronaridine and naphthoquine, were synthesized during the Chinese Project 523 antimalaria drug research effort initiated in 1967; these compounds are all used in combination antimalaria therapies.

Research

Lumefantrine is being investigated as a part of a regimen with ganaplacide for the treatment of Plasmodium falciparum malaria.
Along with O-choline, lumefantrine inhibits in vivo growth of Theileria equi and Babesia caballi, due to inhibition of membrane phospholipid synthesis, hemoglobin digestion and targeting lactate metabolism. Additionally, it can inhibit Babesia gibsoni growth in vitro.
It may exert negative effects on aquatic ecosystems by adversely acting on Chlorella vulgaris, Raphidocelis subcapitata, Lemna minor and Microcystis aeruginosa. Moreover, it is classified as a potential endocrine disrupting compound by decreasing FSHB and increasing prolactin secretion.
Lumefantrine and calcium phosphate-loaded lipid nanoparticles or cubosomes were investigated as a potential treatment of lung cancer due to probable antiangiogenic and anti-inflammatory properties of this combination.
Selenium-containing lumefantrine derivatives synthesised through Knoevenagel condensation exhibit potential antibacterial and antifungal activity. Compared with ciprofloxacin, they were shown to more potently bind to E. coli MurB enzyme – an enzyme participating in cell cycle and cell wall synthesis.