Lumefantrine (or benflumetol) is an antimalarial drug. It is only used in combination with artemether. The term "co-artemether" is sometimes used to describe this combination.
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 Haematin 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 (CYP3A4) and 2D6 (CYP2D6), yielding desbutyl-lumefantrine as a major metabolite.
Adverse effects
Lumefantrine, as used in combination with artemether, was shown to induce the following side effects:
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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
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interactions with CYP3A4 and CYP2D6 inducing or inhibiting drugs
-
infertility (sperm abnormalities and trouble getting pregnant)
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 (octadecyl 2-(trimethylammonio)ethyl phosphate), 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 (synergistically with artemisinin derivatives).
It may exert negative effects on aquatic ecosystems by adversely acting on Chlorella vulgaris, Raphidocelis subcapitata, Lemna minor and Microcystis aeruginosa.
Lumefantrine and calcium phosphate-loaded lipid nanoparticles or Cubosome were investigated as a potential treatment of lung cancer due to probable antiangiogenic and anti-inflammatory properties of this combination.
See also
