Amodiaquine is a 4-aminoquinoline that differs from chloroquine in having a 4-hydroxyanilino function in the side chain. Activity is broadly similar to chloroquine, although amodiaquine is intrinsically more active against Plasmodium falciparum that is moderately resistant to chloroquine.
Mechanism of Action
Amodiaquine interferes with haemozoin formation through complexation with haem.
Mechanism of Resistance
Resistance to amodiaquine occurs through reduced intracellular accumulation. It is likely that mutations in PfCRT also influence in vitro parasite susceptibility to amodiaquine and desethylamodiaquine.
Although rapidly absorbed with a mean tmax of 0.6-1.3h in healthy volunteers, amodiaquine behaves as a pro-drug after oral administration with the principal plasma metabolite monodesethylamodiaquine as the predominant antimalarial species.
25 mg/kg given either as 10 mg/kg followed by 5 mg/kg 6, 24 and 48h thereafter or 10 mg/kg followed by 10 mg/kg at 24h or 5 mg/kg after 48h gives drug concentrations that exceeded MIC’s for chloroquine sensitive strains of Plasmodium falciparum.
The use of amodiaquine in prophylaxis was discontinued due to an unacceptable incidence of agranulocytosis and hepatotoxicity