Disposition of amopyroquin in rats and rabbits and in vitro activity against Plasmodium falciparum

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Abstract
The disposition of amopyroquin was studied in rats after a single 50-mg/kg (body weight) oral dose of amopyroquin base. After a rapid absorption phase, the drug concentrations decreased in the plasma, with a terminal half-life of 14.5 h. The drug was widely distributed in the liver and lungs and, to a lesser extent, in the kidneys and spleen. In rabbits, the kinetic parameters were compared after a single 10-mg/kg dose of amopyroquin base through intravenous, intramuscular (i.m.), and oral routes. The similar bioavailability values (0.67 and 0.69) suggested that the drug could be used through i.m. or oral administration. Clearance and distribution volume did not differ significantly among the three modes of administration, and the terminal half-lives were 18.1 +/- 3.3, 23.9 +/- 6.7, and 25.7 +/- 5.4 h for intravenous, i.m., and oral routes, respectively. The ratio of concentrations in erythrocytes and plasma was about 5 in rats and rabbits. Three metabolites were detected in both animal species (one was tentatively identified as the primary amine derivative). The amopyroquin in vitro activity was tested against four chloroquine-susceptible and 11 chloroquine-resistant African Plasmodium falciparum strains. For all isolates, the 50% inhibitory concentrations of amopyroquin were much lower than those of chloroquine and monodesethylamodiaquine.