Amodiaquine

Class:

Amodiaquine is a 4-aminoquinoline that differs from chloroquine in having a 4-hydroxyanilino function in the side chain.

Antiparasitic Activity:

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.

Pharmacokinetics:

Although rapidly absorbed with a mean tmax of 0.6-1.3h in healthy volunteers, amodiaquine behaves as a prodrug after oral administration with the principal plasma metabolite monodesethylamodiaquine as the predominant antimalarial species.

Dosage:

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.

Adverse Effects:

The use of amodiaquine in prophylaxis was discontinued due to an unacceptable incidence of agranulocytosis and hepatotoxicity