Description
Lumefantrine is a derivative of halofantrine that has been reported to exhibit antimalarial
activity when combined with artemether in the treatment of multidrug-resistant Plasmodium
falciparium . No evidence of cardiotoxicity has been reported with this combination, which
may offer promise for successful treatment of resistant organisms.
Chemical Properties
Yellow Solid
Application
Lumefantrine has been used:
to study its effect on ex-vivo Plasmodium falciparum sensitivity using the tritiated hypoxanthine-based assay
as a standard in the quantification of combined tablet formulation using HPTLC
as a drug molecule in in vitro growth inhibition assay for in vitro B. caballi growth inhibition studies
Uses
A drug used in the treatment of malaria. Antimalarials are usually classified on the basis of their action against Plasmodia at different stages in their life cycle in the human.
Uses
Inhibits hemozoin formation. Antimalarial
Definition
ChEBI: Lumefantrine is an antimalarial drug used in combination with artemether for the treatment of multi-drug resistant strains of falciparum malaria.
Antimicrobial activity
Lumefantrine has marked blood schizonticidal activity against a wide range of plasmodia, including chloroquineresistant P. falciparum. The 50% and 90% effective concentrations (EC50 and EC90) in vitro are similar: <10 and 40 nmol/L, respectively. The racemate and the two enantiomers exhibit similar activities. Blood schizonticidal activity of desbutylbenflumetol is four to five times greater than benflumetol in vitro.
Acquired resistance
Treatment with artemether–lumefantrine can select for polymorphisms
in the P. falciparum pfmdr1 gene. Resistance has
been selected experimentally in murine malaria.
General Description
Lumefantrine was developed in China. Itsmechanism of action is poorly understood. There is some evidencethat it inhibits the formation of β-hematin by forming acomplex with hemin. Lumefantrine is very lipophilic and is marketed in combination with the lipophilic artemesininderivedartemether.
Pharmaceutical Applications
A dichlorobenzylidene derivative given orally in combination
with artemether.
Biochem/physiol Actions
Lumefantrine is is an antimalarial for the treatment of multi-drug resistant strains of falciparum malaria.
Pharmacokinetics
Bioavailability after oral administration is variable; absorption
is substantially increased by co-administration with food,
particularly
with a high fat content. Peak plasma concentrations
occur after 6–8 h. The elimination half-life is 4–6 days. It
is almost completely protein bound and metabolized mainly
in the liver by CYP3A4.
Clinical Use
Treatment of P. falciparum infections (including mixed infections)
in a fixed-dose combination treatment with artemether.
Side effects
The most common adverse effects in combination with artemether
include headache, dizziness and gastrointestinal disturbances.
Synthesis
Lumefantrine is chemically linked to water-soluble polymers, such as polyethylene glycol and poly-acryloylmorpholine derivatives, via hydrolysable bonds to synthesize water-soluble polymer conjugates.
Metabolism
Primaquine is almost totally metabolized by CYP3A4 (99%), with the primary metabolite being
carboxyprimaquine. Trace amounts of N-acetylprimaquine plus aromatic
hydroxylation and conjugation metabolites also have been reported.
References
[1] AURéLIE PASCUAL. Ex vivo activity of the ACT new components pyronaridine and piperaquine in comparison with conventional ACT drugs against isolates of Plasmodium falciparum.[J]. Malaria Journal, 2012, 11: 45. DOI:
10.1186/1475-2875-11-45[2] HELENA H ASKLING. Management of imported malaria in Europe.[J]. Malaria Journal, 2012, 11: 328. DOI:
10.1186/1475-2875-11-328[3] MAYFONG MAYXAY. Efficacy of artemether-lumefantrine, the nationally-recommended artemisinin combination for the treatment of uncomplicated falciparum malaria, in southern Laos.[J]. Malaria Journal, 2012, 11: 184. DOI:
10.1186/1475-2875-11-184[4] Lü-PEI DU . The pharmacophore hypotheses of IKr potassium channel blockers: novel class III antiarrhythmic agents[J]. Bioorganic & Medicinal Chemistry Letters, 2004, 14 18: Pages 4771-4777. DOI:
10.1016/j.bmcl.2004.06.070
