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
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.
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.
