Comparison of the in-vitro activity of amodiaquine and its main metabolite, monodesethyl-amodiaquine, in Plasmodium falciparum.

After its rehabilitation for therapeutic use in uncomplicated falciparum malaria, there is renewed interest in amodiaquine. After oral administration, the drug undergoes rapid metabolism to monodesethyl-amodiaquine, and in patients with normal hepatic function the parent drug usually becomes undetectable within a few hours. The main antimalarial activity is therefore mainly due to the metabolite. In a comparative study in northwestern Thailand, 21 fresh isolates of Plasmodium falciparum were tested, in parallel, for their in-vitro sensitivity to both compounds, using the WHO micro-test Mark II, measuring the inhibition of schizont maturation. The geometric mean cut-off concentrations of schizont maturation were 1826 nM (related to blood) for amodiaquine, and 1654 nM for monodesethyl-amodiaquine. The log-probit regressions for both compounds showed good fits to the data points. The EC50 values were 331 nM and 291 nM, and the EC90 values 1337 nM and 993 nM for amodiaquine and monodesethyl-amodiaquine, respectively. Differences between regression slopes and effective concentrations were well below statistical significance. Both compounds showed highly significant activity correlation. These findings suggest that the sensitivity of Plasmodium falciparum to amodiaquine closely reflects its sensitivity to monodesethyl-amodiaquine.