Lumefantrine Chemische Eigenschaften,Einsatz,Produktion Methoden
Beschreibung
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.
Chemische Eigenschaften
Yellow Solid
Verwenden
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
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 (EC
50 and EC
90) 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.
Allgemeine Beschreibung
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.
Pharmazeutische Anwendungen
A dichlorobenzylidene derivative given orally in combination
with artemether.
Pharmakokinetik
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.
Nebenwirkungen
The most common adverse effects in combination with artemether
include headache, dizziness and gastrointestinal disturbances.
Stoffwechsel
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.
Lumefantrine Upstream-Materialien And Downstream Produkte
Upstream-Materialien
Downstream Produkte
